Frequency–current relationships of rat hindlimb α-motoneurones
J Physiol573.3(2006)pp663–677663 Frequency–current relationships of rat hindlimb
α-motoneurones
Duane C.Button,Kalan Gardiner,Tanguy Marqueste and Phillip F.Gardiner
Spinal Cord Research Center,Department of Physiology,University of Manitoba,Canada
The purpose of this study was to describe the frequency–current(f–I)relationships of hindlimb
α-motoneurones(MNs)in both anaesthetized and decerebrate rats in situ.Sprague–Dawley rats
(250–350g)were anaesthetized with ketamine and xylazine(KX)or subjected to a precollicular
decerebration prior to recording electrophysiological properties from sciatic nerve MNs.
Motoneurones from KX-anaesthetized rats had a signi?cantly(P<0.01)hyperpolarized resting
membrane potential and voltage threshold(V th),increased rheobase current,and a trend
(P=0.06)for a smaller after-hyperpolarization(AHP)amplitude compared to MNs from
decerebrate rats.In response to5s ramp current injections,MNs could be categorized into four
f–I relationship types:(1)linear;(2)adapting;(3)linear+sustained;and(4)late acceleration.
Types3and4demonstrated self-sustained?ring owing to activation of persistent inward current
(PIC).We estimated the PIC amplitude by subtracting the current at spike derecruitment
from the current at spike recruitment.Neither estimated PIC nor f–I slopes differed between
fast and slow MNs(slow MNs exhibited AHP half-decay times>20ms)or between MNs
from KX-anaesthetized and decerebrate rats.Motoneurones from KX-anaesthetized rats
had signi?cantly(P<0.02)hyperpolarized ramp V th values and smaller and shorter AHP
amplitudes and decay times compared to MNs from decerebrate rats.Pentobarbitone decreased
the estimated PIC amplitude and almost converted the f–I relationship from type3to type1.In
summary,MNs of animals subjected to KX anaesthesia required more current for spike initiation
and rhythmic discharge but retained large PICs and self-sustained?ring.The KX-anaesthestized
preparation enables direct recording of PICs in MNs from intact animals.
(Received10February2006;accepted after revision6April2006;?rst published online13April2006)
Corresponding author P.Gardiner:Spinal Cord Research Center,Department of Physiology,University of Manitoba,
730William Avenue,436BMSB,Winnipeg,Manitoba,Canada R3E3J7.Email:gardine2@cc.umanitoba.ca
The frequency–current(f–I)relationships of motoneurones(MNs)demonstrate several non-linearities,which re?ect their active properties in response to suprathreshold current injections.The f–I relationship derived from short duration square-wave intracellular current injection can be described by several ranges: (1)primary;(2)secondary;and(3)tertiary(Kernell, 1965b,c;Schwindt,1973).Longer duration current pulses are accompanied by a decrease in MN?ring frequency (FF)known as spike-frequency adaptation,which can be described in three stages:(1)initial;(2)early;and (3)late(Granit et al.1963;Kernell,1965a,b;Kernell& Monster,1981;Sawczuk et al.1995;Powers et al.1999; Powers&Binder,2001;Miles et al.2005).More recently, square-wave and triangular current pulses have been used to determine MN f–I relationships and the effect of persistent inward currents(PICs)on these relationships (Hounsgaard et al.1988;Lee&Heckman,1998a;Bennett et al.2001).
Persistent inward currents in MNs are depolarizing currents generated by non-inactivating or slowly inactivating voltage-gated Na+and Ca2+channels(Lee& Heckman,1999;Li&Bennett,2003),when the membrane potential is depolarized above their activation threshold. These currents can mediate a plateau potential that in turn allows the MN to express self-sustained rhythmic ?ring.A plateau potential can be initiated by a short depolarizing current pulse and remain for a long period of time before being terminated either spontaneously or by brief hyperpolarizing current(Kiehn&Eken,1998). This property allows a MN to?re for a long period of time.Thus,a MN can behave in a‘bistable’manner,in that it can be toggled between an active and a quiescent state.Furthermore,a MN PIC can be ampli?ed by a host of neurotransmitters and neuromodulators(Heckman et al.2004).Neuromodulatory input to a MN via axons originating in the ralphe nucleus and locus coeruleus of the brainstem releases the monoamines serotonin(5-HT;
C 2006The Authors.Journal compilation C 2006The Physiological Society DOI:10.1113/jphysiol.2006.107292
664 D.C.Button and others J Physiol573.3
Hounsgaard et al.1988;Skydsgaard&Hounsgaard,1996)
and noradrenaline(NA;Lee&Heckman,2000),which
can enhance the PIC and render the motoneurone more
excitable(Gilmore&Fedirchuk,2004).
A plateau potential and its underlying PIC that conduct
through voltage-gated ion channels have been examined
in both in vivo and in vitro animal models through
the use of voltage-clamp(Schwindt&Crill,1977,1981,
1982;Bennett et al.2001)and current-clamp techniques
(Hounsgaard et al.1988;Lee&Heckman,1998a;Bennett
et al.2001)with a concurrent addition of speci?c
voltage-gated ion channel agonists,antagonists and neuro-
modulators.The current-clamp technique,in the form of
a triangular current pulse(referred to as ramp current
hereafter),has been used as a tool to determine f–I
relationships and to estimate the associated PIC(ePIC)of
hindlimbα-MNs in cats in vivo(Hounsgaard et al.1988;
Lee&Heckman,1998a)and rat tail MNs in vitro(Bennett
et al.2001).However,this technique has not been used
to determine the ePIC or describe f–I relationships in rat
hindlimbα-MNs in situ.The?rst purpose of this paper
is to determine whether hindlimbα-MNs of our in situ
rat preparation demonstrate ePICs and f–I relationship
patterns that are comparable with those reported by
Bennett et al.(2001).
In previous studies,the ePIC was de?ned by
subtracting the current at which MN rhythmic?ring
spike derecruitment occurs from the current at which
MN rhythmic?ring spike recruitment occurs.The plateau
potential or underlying PIC appears as a steep rise
in?ring frequency in the f–I relationship.In other
words,a MN?ring pattern elicited by a ramp current
illustrates the plateau current as an counter-clockwise f–I
hysteresis(Hultborn,1999).Furthermore,it has been
shown that bistable MNs have lower rheobase currents,
suggesting that smaller MNs are in?uenced by PIC in
a different manner from bigger MNs(Lee&Heckman,
1998a).Although this technique has been described
as a meaningful way to estimate the size of the PIC
and to illustrate MN f–I relationships as well as the
PIC relationship to passive properties,other important
information remains to be uncovered.Some further
questions include the following.(1)Does the ePIC
correlate with other passive MN properties?(2)Does MN
ePIC change owing to the history(e.g.blood pressure,
time of day,CO2levels)of the experimental preparation?
(3)Will the ePIC depend on the duration of the glass
microelectrode impalement of the MN?(4)Do voltage
threshold(V th),after-hyperpolarization(AHP)amplitude
and AHP3/4decay time change from spike to spike throughout the ramp?Thus,the second purpose of this
paper is to attempt to answer this series of questions
pertaining to ePIC.
It has been suggested(Hultborn&Kiehn,1992;
Hultborn,1999)that,owing to the masking effects of anaesthetics,PICs were not evident in previous
experiments in which animals were anaesthetized with
barbiturates.More recently,it has been shown that
in decerebrate animals compared to animals deeply
anaesthetized with pentobarbitone,current generated by
stimulation of muscle spindle Ia afferents was ampli?ed
four times by active dendritic currents(Lee&Heckman,
2000).Furthermore,when pentobarbitone was added to
an in vitro turtle spinal cord slice preparation,plateau
potentials were no longer seen in MNs(Guertin&
Hounsgaard,1999).We wished to determine how the
addition of pentobarbitone to an in situ rat preparation
would affect the MN ePIC and the f–I relationship.
Finally,we anaesthetized the rat with a
ketamine–xylazine(KX)mixture.Xylazine is an α2-adrenoceptor agonist,which should not in?uence the amplitude or activation of PIC.In contrast,ketamine is
an N-methyl-d-aspartate(NMDA)receptor antagonist
(Liu et al.2001).These receptors are present in adult
turtle MNs(Guertin&Hounsgaard,1998)and neonatal
rat MNs(Hochman et al.1994;Palecek et al.1999;Hsiao
et al.2002).Hochman et al.(1994)demonstrated that
NMDA-induced rhythmic membrane voltage oscillations
revealed the presence of bistable membrane properties.
Little is known about the role of NMDA receptors in MNs
of adult mammalian preparations,however,and it has been
shown(see above)that,in adult mammalian preparations,
PICs conduct through Na+and Ca2+channels.Thus,the
?nal purpose of the present paper is to determine whether
KX anaesthesia in?uences rat hindlimbα-MN ePIC
and f–I relationship.A portion of these results has been
presented elsewhere in abstract form(Button et al.
2005a,b).
Methods
Treatment of animals
Female Sprague–Dawley rats weighing275–325g were
obtained from the University of Manitoba(Winnipeg,
Manitoba,Canada),and initially housed in groups of two
in plastic cages situated in an environmentally controlled
room maintained at23?C and kept on a12h–12h
light–dark cycle.The rats were provided with water and
food ad libitum throughout the experiment.Rats(n=20)
underwent experimental procedures within7days of
receipt.All procedures were approved by the animal ethics
committee of the University of Manitoba and were in
accordance with the guidelines of the Canadian Council
of Animal Care.
Surgery
For these terminal experiments,rats were taken from their
cages and anaesthetized with ketamine and xylazine(80
and10mg kg?1,respectively,i.p.).Each rat also received
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol573.3Frequency–current relationships of motoneurones665
an intraperitoneal injection(volume 6.6ml kg?1) of saline containing5%dextrose and0.05mg kg?1 atropine.Brie?y,the anaesthetized rat was surgically prepared for electrophysiological recording via impalement of spinal motoneurones following:(1)a tracheotomy;(2)catherization of the femoral artery;
(3)an incision to allow stimulation of the sciatic nerve of the left hindlimb;(4)exposure,removal and cleaning of the spinal vertebrae in preparation for the laminectomy; and(5)a laminectomy from T12to S1.Following the tracheotomy,the rat was ventilated(Harvard Apparatus, Canada)with pure oxygen-enriched room air,at a tidal volume of approximately2ml,and a ventilation rate of approximately60–80strokes min?1.Expired carbon dioxide levels were measured via a CAPSTAR100 CO2analyser(CWE Inc.Ardmore,PA,USA)and were maintained between3.0and4.0%.Mean arterial pressure(MAP;Pressure Monitor BP-1;World Precision Instruments,Sarasota,FL,USA)was also measured and maintained between80and110mmHg.Anaesthesia was maintained by constant infusion of a physiological saline solution containing ketamine and xylazine(9and 1mg h?1,respectively)via the femoral artery catheter (Pump11,Harvard Apparatus).The depth of anaesthesia was veri?ed frequently via MAP and CO2levels and toe pinch and eye blink re?exes.
Following exposure and cleaning of the spinal vertebrae, the rat was transferred to a stereotaxic unit in preparation for the laminectomy.Rectal temperature was monitored and maintained near37?C using a Homeothermic Blanket Control Unit(Harvard Apparatus).The head,thoracic and lumbar vertebrae,hips and left foot were immobilized with clamps,and the open leg and back incisions were ?lled with mineral oil.The dura mater covering the spinal cord was incised,and the large dorsal roots comprising afferents from the left hindlimb were cut and re?ected over the right side of the cord.An opening was made in the pia mater just lateral to the entry zone of these roots into the cord,in preparation for introduction of the glass microelectrode.Immediately before beginning the search for motoneurones,a pneumothorax was performed by making a5mm incision between ribs T5and T6on the left side of the thorax.
In another series of experiments,rats were initially anaesthetized with iso?uorane and the surgical procedures stated above were performed.In addition to these procedures,the carotid arteries were separated from vagal, aortic and sympathetic nerves and ligated.The carotid arteries were then cannulated towards the head with short saline-?lled tubing.The other end of the tubing was connected to a20gauge syringe needle used to inject 0.06–0.07ml of mixed polyvinylsiloxane(PVS;extrude from Kerr or Reprosil from Dentsply Caulk,medium and heavy body)into each carotid artery via a1ml syringe. The PVS entered into the external and internal carotid arteries,?lling all arteries that these vessels supplied.Once the vessels were?lled,a precollicular decerebration was performed(for details of the decerebration procedure see Fouad&Bennett,1998).Upon the decerebration, anaesthesia was terminated and the rat was allowed to stabilize for1h before electrophysiological recordings began.
Drugs and solutions
To reduce blood pressure and respiration-related movement artifacts and to stabilize the rat for proper electrophysiological recordings,several solutions were injected intravenously,as follows:(1)a solution of100m m of NaHCO3(Fisher scienti?c)and5%dextrose(Fisher Scienti?c)dissolved in25ml of distilled deionized H2O;(2)300mosmol l?1of Ficoll70(Sigma)dissolved in normal saline,which was used as a plasma expander;and(3)pancuronium bromide(0.2mg kg?1), as a muscle relaxant.The pancuronium bromide was injected intravenously immediately before the start of electrophysiological recordings and was re-administered upon the reappearance of muscle contraction in response to sciatic nerve stimulation.Upon the addition of pancuronium bromide,depth of anaesthesia was monitored by MAP.In one experiment,sodium pento-barbitone(50mg kg?1)was administered intravenously to determine the effect,if any,on the PIC(Guertin& Hounsgaard,1999;Lee&Heckman,2000). Measurement of motoneurone properties
Thin-walled glass microelectodes(1.0mm,World Precision Instruments,Sarasota,FL,USA)were pulled (Kopf Vertical Pipette Puller,David Kopf Instruments, Tujurga,CA,USA),and?lled with2m potassium citrate. Electrode impedances were approximately10M .The tip of the electrode was positioned at a hole in the pia mater and was lowered with an inchworm microdrive system(Burleigh Instruments Inc.,NY,USA)into the cord in steps of10μm.The sciatic nerve was stimulated with a bipolar silver electrode at a frequency of1s?1, while the microelectrode was advanced through the cord and the?eld potential was continuously monitored. In some experiments,a?ne-wire tungsten electrode (World Precision Instruments,5M )was used to identify the location and depth in the spinal cord where the?eld potential was the largest.Evidence of successful impalement of anα-MN was a sudden increase in potential to at least?50mV,and an antidromic action potential with a spike amplitude of>55mV and a reproducible latency of less than2.5ms from the stimulation artifact.When recording had stabilized for at least2min,resting membrane potential was recorded. During recording,an axoclamp intracellular ampli?er system(Axoclamp2B,Axon Instruments Inc.,Union City,
C 2006The Authors.Journal compilation C 2006The Physiological Society
666 D.C.Button and others
J Physiol 573.3
CA,USA)was used,either in bridge or discontinuous current-clamp modes (DCC;2–3kHz switching),with capacitance maximally compensated.The following passive MN properties were recorded in bridge mode:antidromic action potential (from an average of 10spikes),and orthodromic action potential in response to a 0.5ms current pulse of supramaximal intensity (from an average of 40spikes).Rheobase current (50ms square-wave current amplitude resulting in spikes 50%of the time)and cell input resistance (from an average of 60,1nA hyperpolarizing pulses each lasting 100ms)were recorded in DCC mode.From these recordings we determined antidromic spike height and time course,amplitude and half-decay time of the AHP following an action potential evoked by a 0.5ms current pulse,resting membrane potential (RMP),rheobase current,voltage threshold and cell input resistance (IR).The half-decay time of the AHP was used to separate ‘slow’from ‘fast’MNs,as we have done previously (Beaumont &Gardiner,2002,2003).
2
4
6
8
10
12
s -60-40-20020C u r r e n t (n A )
M e m b r a n e p o t e n t i a l (m V )
02
4
6
10
14
18
22
4.7
5.1
5.5 5.9
6.3
Current (nA)
F i r i n g F r e q u e n c y (H z )
A
B
Figure 1.f–I relationships determined by using 5s up–down ramp injections
A ,the top trace is the rhythmic discharge of the MN in response to a ramp current (bottom trace).Arrows point to the current at spike recruitment and spike derecruitment.Estimated PIC (ePIC)was calculated by subtracting the current at spike derecruitment from the current at spike recruitment.
B is a plot of the instantaneous ?ring frequency and current from traces in A .In this example,the f–I relationship was plotted as an counter-clockwise hysteresis.
Measurement of motoneurone f–I relationship
After measuring MN passive properties,cells were then challenged with slow triangular current ramps (range:0.5–6.0nA s ?1),and the voltage response was measured in DCC mode.Peak amplitude of the ramp depended entirely on the rhythmic threshold of the MNs,and an attempt was made to evoke trains of impulses containing 10–75spikes over a 0.5–2.5s duration.Ramps were used to determine the MN f–I relationship,to evoke voltage-dependent plateaus and to measure the underlying PIC as previously described (Hounsgaard et al.1988;Lee &Heckman,1998a ;Bennett et al.2001).During the current ramps,the ePIC producing the plateau and sustaining ?ring was estimated from the difference in injected current at spike recruitment compared with spike derecruitment (see Fig.1;Lee &Heckman,1998a ;Bennett et al.2001).For computing the average f–I relationship type and ePIC for each MN,we used a series of three to six current ramps.Voltage thresholds of the spikes elicited
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol573.3Frequency–current relationships of motoneurones667 Table1.Passive and active motoneurone properties
Motoneurone property KX fast cells KX slow cells Decerebration fast cells P value
(1)RMP(mV)?70.9±6.3?64.2±5.9?61.7±7.8?0.005
(2)V th(mV)?51.6±6.6?46.1±11.7?45.6±7.2?0.02
(3)Rheobase current(nA)9.8±3.0 5.9±4.7 6.4±1.8?0.01
n=21n=7n=14?0.01 (4)Input resistance(M ) 1.8±0.6 2.7±1.2 2.2±0.9?0.01
n=21n=7n=14
(5)AHP amplitude(mV) 1.5±1.1 2.7±2.1 2.6±2.20.06
(6)AHP1/2decay time(ms)13.8±1.927.3±6.612.7±2.9?0.00
n=21n=7n=14
(7)Current at spike recruitment(nA)11.0±3.17.4±3.9 6.9±4.0?0.004
n=21n=7n=14?0.001 (8)Current at spike derecruitment(nA)10.9±3.17.0±4.0 6.6±4.2?0.01
n=21n=7n=14?0.001 (9)Instantaneous frequency at spike recruitment(Hz)26.5±7.716.7±7.219.0±6.7?0.003
n=21n=7n=14?0.003 (10)Instantaneous frequency at spike derecruitment(Hz)24.7±6.814.1±5.616.3±4.6?0.000
n=21n=7n=14?0.000 (11)Slope(Hz nA?1)depolarizing17.8±9.715.3±8.515.1±11.00.6
n=21n=7n=14
(12)ePIC(nA)0.2±0.60.4±0.30.3±0.50.6
n=21n=7n=14
Summary of passive(numbers1–6in chart)and active MN properties(numbers7–12in chart).Data are presented as means±1S.D.for MNs in each group and include all f–I relationship types.KX,ketamine–xylazine anaesthetized;RMP,resting membrane potential;V th, voltage threshold;AHP,after-hyperpolarization;and ePIC,estimated persistent inward current.?Signi?cant difference between KX fast and slow motoneurones;?signi?cant difference between KX fast and decerebration fast motoneurones.
during the ramp were measured at the potential where there was an acceleration in the rate of depolarization to>10mV(2ms)?1(modi?ed from Brownstone et al. 1992).
At the end of these measurements,the microelectrode was backed out of the MN in5μm steps,and the voltage outside the cell was recorded.Typically,experiments yielded two MNs with complete complements of data.At the end of the experiment,the rat was killed by an overdose of KCl which was injected intravenously.
Statistics
Only MNs that responded rhythmically to ramp currents and passed all electrophysiological requirements were used in the analysis.The MN passive properties and rhythmic properties were subjected to a one-way analysis of variance (ANOV A)for MN type and group(since all of the decerebration MNs which met the criteria for analysis were of the fast type).Motoneurones were designated as fast or slow based on the half-decay time of the AHP (fast,<20ms;slow,>20ms).This was done in order to subgroup MNs based on an intrinsic property that covaries highly with muscle?bre type and excitability,and which remains relatively stable in a variety of conditions that evoke changes in other properties(Zengel et al. 1985;Gardiner,1993;Gardiner&Seburn,1997;Munson et al.1997;Cormery et al.2000).To determine whether signi?cant differences were present in MN f–I relationship type,X2analysis was used.Some MN rhythmic properties were subjected to a two-way ANOV A procedure on factors of group and spike numbers(see Results for details). Where a signi?cant interaction term was present,data were subjected to a Tukey post hoc comparisons test,to determine signi?cant differences among individual means. All data are expressed as means±1s.d.
Results
We recorded data from29MNs in14rats that were anaesthetized with ketamine and xylazine.The data set is summarized in Table1.We separated MNs into‘fast’and‘slow’,using the half-decay time of the AHP.This is based on previous reports(Gardiner,1993;Cormery et al. 2000,2005)that rat hindlimb MNs with AHP half-decay times equal to or greater than20ms innervate slow-twitch muscle?bres.
Motoneurone properties of KX-anaesthetized rats The one-way ANOV A test revealed signi?cant main effects of MN type(fast versus slow)for several electro-physiological properties.Motoneurone passive and f–I relationship properties are summarized in Table1(passive properties are listed from1to6and f–I relationship properties are from7to12).Fast MNs required35% more current for spike generation in response to50ms
C 2006The Authors.Journal compilation C 2006The Physiological Society
668 D.C.Button and others J Physiol573.3 Table2.Summary of f–I relationship types
f–I relationship type
Type1:Type2:Type3:linear Type4:
overlapping adapting+sustained acceleration
Number(n)n%n%n%n%
All MNs4371712281943512
KX fast MNs22418732115000
KX slow MNs711500457228
Decerebration fast MNs14214536428322
square-wave current pulses compared to slow MNs.Input resistance and AHP amplitude were34and45%smaller, respectively,for fast MNs compared to slow MNs.During a ramp current,fast MNs required32%more current to initiate?ring and35%more current to terminate rhythmic?ring compared to slow MNs.Furthermore,the minimum instantaneous?ring frequencies of fast MNs were signi?cantly higher at spike recruitment(36%)and derecruitment(42%)compared to slow MNs.The average ePIC was not signi?cantly different between fast and slow MNs.
Types of f–I relationships
We injected ramps of current into the MNs and determined their f–I relationship type(see Table2for f–I relationship distributions).This method has been used previously (Hounsgaard et al.1988;Lee&Heckman,1998a;Bennett et al.2001)to determine f–I relationships and as a way to estimate the PIC(see Fig.1).Similar to the four f–I relationship types demonstrated in rat sacral motoneurones in vitro(Bennett et al.2001),in situ rat hindlimbα-MNs could also be categorized into the same four f–I relationship types.The f–I relationship types are shown in Fig.2A–D.Type1(n=7,17%) MN f–I relationship demonstrated a?ring frequency slope(average24.3±9.5Hz nA?1)that overlaps on the ascending and descending portions of the ramp current (Fig.2A).Type2(n=12,28%)MN f–I relationship demonstrated a clockwise hysteresis(i.e.MN?ring rate adaptation)where the?ring frequencies were greater during the ascending versus the descending portion of the ramp at any given current and the average slope values of the up and down portions of the ramp current were 12.6±8.4and18.9±10.4Hz nA?1,respectively(Fig.2B). Type3(n=19,43%)MN f–I relationship demonstrated a linear regression line with some self-sustained?ring corresponding to the tertiary range of?ring(Li et al. 2004;i.e.activation of a PIC)and an average slope of 15.8±6.8Hz nA?1(Fig.2C).Type4(n=5,12%)MN f–I relationship demonstrated a counter-clockwise hysteresis or an acceleration of?ring just after spike recruitment and below the linear regression line(i.e.activation of a PIC)corresponding to the secondary range of?ring. None of these MNs demonstrated a primary range of ?ring but rather started?ring in the secondary range followed by shallower sloped tertiary range(see Fig.5of Li et al.(2001)for further description of these three?ring ranges during a ramp).The type4f–I relationship?ring frequencies were greater during the descending versus the ascending portion of the ramp at any given current,and the average slope values of the up and down portions of the ramp current were16.7±18.6(secondary range)and 10.1±2.6Hz nA?1(tertiary range),respectively.There were no signi?cant f–I slope differences among f–I relationships or between MN types.However,there was a trend(P=0.08)for a decreased slope during the down portion of the ramp in the f–I relationship type4compared to the other f–I relationship types.
ePIC amplitudes of f–I relationship types3and4 Frequency–current relationship types3and4were shown in approximately60%of MNs from which we recorded. These relationship types demonstrate activation of a PIC.During the ePIC,?ring frequencies were decreased by approximately15%in both fast(30Hz at spike recruitment versus25.5Hz at spike derecruitment)and slow MNs(15.2Hz at spike recruitment versus12.9Hz at spike derecruitment).Figure3illustrates a distribution of average ePIC measured from f–I relationship types3and4. For any given cell,if the initial ramp elicited a PIC,all sub-sequent ramps did so as well.In most of the motoneurones the ePIC amplitude was consistent from ramp to ramp even when the ramp current was increased or decreased. Although ePIC amplitude did not differ among fast and slow MNs,χ2analysis revealed a tendency(P=0.09)for a greater proportion of slow MNs(87%)to demonstrate types3and4f–I relationships compared to fast MNs (50%).
Lastly,the ePIC was not correlated with the animal’s vital signs(blood pressure or CO2levels)throughout the experiment.There was,however,a trend(P=0.08)for the ePIC to be negatively correlated(?0.44)with time of day during the experiment.
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol 573.3
Frequency–current relationships of motoneurones 669
Effect of sodium pentobarbitone on MN ePIC amplitude in a KX-anaesthetized rat
In one experiment,we applied a series of ramps to a MN before and after the intravenous administration
M e m b r a n e P o t e n t i a l (m V )
C u r r e n t (n A )
M e m b r a n e P o t e n t i a l (m V )
C u r r e n t (n A )M e m b r a n e P o t e n t i a l (m V )
C u r r e n t (n A )M e m b r a n e P o t e n t i a l (m V )
C u r r e n t (n A )Time (s)
-400024Current (nA)
-4000
4812
04812A
B
C
D
Figure 2.A ,B ,C and D represent four different ramp-induced f–I relationship types;left is the raw ramp data and right is the plotted f–I relationship
A ,type 1MN f–I relationship demonstrates a ?ring frequency slope that overlaps on the ascending and descending current ramps.
B ,type 2MN f–I relationship demonstrates a clockwise hysteresis (MN ?ring rate adaptation).
C ,type 3MN f–I relationship demonstrates a linear regression line (upper portion of graph)with some self-sustained ?ring.
D ,type 4MN f–I relationship demonstrates a counter-clockwise hysteresis or an acceleration of ?ring just after spike recruitment and below the linear regression line.
of sodium pentobarbitone.In total,the MN was impaled for 80min.Before the addition of pento-barbitone,the ePIC amplitude average over ?ve ramps was 0.52nA.This was signi?cantly (P <0.001)higher than the ePIC amplitude average over the last ?ve
C 2006The Authors.Journal compilation C 2006The Physiological Society
670 D.C.Button and others
J Physiol 573.3
ramps recorded 40–60min following the ?rst injection of pentobarbitone (0.16;see Fig.4A ).Furthermore,the f–I relationship type was converting from type 3to type 1(see Fig.4B ).Although ePIC amplitudes decreased,the passive properties RMP,V th ,rheobase,AHP amplitude and duration)remained similar (not shown)before and after the addition of pentobarbitone.Because the MN had been impaled for a long time before the administration of pento-barbitone,we wished to demonstrate that the changes in ePIC were due to the drug rather than impalement time.Therefore,in another experiment we impaled a MN for 90min without the addition of pentobarbitone and sub-jected it to a series of ramps.The ePIC amplitude for this neurone was virtually the same at minute 1(0.55±0.09nA)and minute 90(0.56±0.08nA;see inset in Fig.4A ).
Voltage threshold and AHP properties of ramp spikes in KX-anaesthetized rats
We also analysed V th ,AHP amplitude and 3/4decay time of the AHP for the initial three spikes during the depolarizing current phase of the ramp,the three spikes at the same current during the repolarizing current phase of the ramp and,when applicable,the last three spikes triggered during the ePIC (see Fig.5A and B for details)from nine fast and six slow MNs (which demonstrated all 4types of f–I relationships).Similar to a short orthodromic spike,the AHP amplitudes and durations of spikes during current ramps were smaller and shorter in fast MNs (see Table 3).Most importantly,irrespective of MN or f–I relationship type,V th and AHP properties during a ramp were no
0123456789101112131415161718
Motoneurone number
e P I C A m p l i t u d e (n A )
Figure 3.Recordings from MNs demonstrating type 3and 4f–I relationships
Each data point represents the ePIC amplitude of a MN subjected to a series of ramps (minimum of at least three).The grey and white squares represent fast and slow MNs,respectively.The dashed line represents the mean ePIC for all cells.Data points are presented as means ±1S .D .
different from spike to spike (see Fig.6).Figure 6(which includes all spikes as opposed to the 9we measured)shows V th values and AHPs for all of the ramp spikes shown in Fig.5A .For this cell,spike recruitment was induced at 17.4nA and spike derecruitment occurred at 16.1nA.During this current,the cell generated a total of 19spikes (12of which occurred below the current at which spike recruitment was initiated).Voltage threshold at each spike ranged from ?42.7to ?46.5mV ,AHP amplitude ranged from 12to 16mV,and the AHP 3/4decay time ranged from 25to 42ms.Voltage threshold was consistent throughout.However,the AHP amplitude and duration increased and decreased as ramp current increased and decreased,producing a greater range in the AHP properties.The voltage threshold and AHP properties measured at the ?rst and last spikes were very similar in almost every ramp regardless of the MN f–I relationship type (see Fig.5C ).In Fig.5C ,spikes 1,18,and 19are at a higher gain then shown in Fig.5A ,and Table 4summarizes V th and AHP values recorded from the spikes.
The effect of KX versus decerebration on motoneurone properties
During another set of experiments,we recorded from 14MNs in six rats that were subjected to precollicular decerebration.All decerebration MNs that met the criteria for analysis were of the fast type.This was due to sampling error,since we did record from some decerebrated MNs with AHP 1/2decay times greater than 20ms,and therefore not because of any effect of the decerebration on MN AHP time course.One limitation in this study is that we compared MNs from an intact anaesthetized animal to a non-intact non-anaesthetized animal.This limitation could be alleviated in the future by comparing MNs from decerebrate animals to KX-treated decerebrate animals.Nonetheless,the one-way ANOV A revealed signi?cant main effects of group (KX versus decerebration)for several electrophysiological properties of fast MNs (see Table 1for details).Motoneurones from KX-anaesthetized rats had signi?cantly hyperpolarized (14%)RMP and V th ,required 40%more current for spike triggering and had 45%smaller AHP amplitudes compared to MNs from decerebrate animals.During a ramp the MNs from KX-anaesthetized rats required 37and 38%more current and their instantaneous ?ring frequencies were 28and 34%higher at spike recruitment and derecruitment,respectively,compared to MNs from decerebrate animals.Motoneurones from KX-anaethetized and decerebrate rats demonstrated similar f–I relationship types (see Fig.2)and distributions (see Table 2).Furthermore,decerebration (0.7±0.4nA)and KX (0.6±0.4nA)motoneurone mean ePIC amplitudes measured from the MNs demonstrating type 3and 4f–I relationships were also similar (see Fig.7A ).Furthermore,ePIC
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol 573.3
Frequency–current relationships of motoneurones 671
amplitude did not correlate with MN input resistance in KX-anaesthetized (P =0.9)or decerebrate rats (P =0.3;Fig.7B ).
For MNs from KX-anaethetized rats,the V th values of spikes during current ramps were 11%hyperpolarized,had 9%smaller AHP amplitudes and 45%longer AHP 3/4decay times compared to MNs from decerebrate rats (see Table 3for details).Similar to MNs from KX-anaethetized
Time (min)
18
26
-0.4
0.0
0.4
0.81.2
e P I C a m p l i t u d e (n A )
4
31
35
44
49
55
62720
2040608012
13
14
15
11.4
11.812.212.6
Current (nA)
F i r i n g F r e q u e n c y (H z
)
A
B
Figure 4.The effect of pentobarbitone on MN ePIC amplitude and f -I relationship
A ,data were recorded from one MN.Each data point represents the ePIC amplitude average from of a series of ramps (minimum of at least three)at each time period before and after the addition of pentobarbitone.Arrows indicate when pentobarbitone was injected into the rat.The inset indicates that the ePIC does not depend on the time course of the glass microelectrode impalement of the motoneurone.
B ,left is a graph showing the MN f–I relationship (type 3).Its response to a 5s ramp current injection was measured before the addition of pentobarbitone.Right is a graph demonstrating that upon injection of pentobarbitone,the f–I relationship of the MN is almost converted (within 1h of motoneurone impalement)from f–I relationship type 3to type 1.
rats,for MNs from decerebrate rats the V th values and AHP properties during a ramp were no different from spike to spike (see Fig.6).Discussion
The most important ?nding of this study is that rat hindlimb α-motoneurones injected with ramp currents
C 2006The Authors.Journal compilation C 2006The Physiological Society
672 D.C.Button and others
J Physiol 573.3
resulted in four types of f–I relationships,two of which demonstrated a presence of persistent inward current.The four f–I relationship types are similar to those noted previously in vitro for rat sacral MNs (Bennett et al.2001).Moreover,it appears that the ePIC amplitude is not dependent on MN type,which has been indirectly addressed previously in cat lumbar α-MNs (Lee &Heckman,1998a )and rat sacral–caudal MNs (Bennett et al.2001).However,f–I relationship types 3and 4
tend
M e m b r a n e p o t e n t i a l (m V )
-40
-200C u r r e n t (n A )
16
17
A
-40
-20
11819
20 ms
C
M e m b r a n e p o t e n t i a l (m V )Figure 5.Voltage thresholds,AHP amplitudes and AHP 3/4durations measured during the ramp
A ,voltages and currents at which rhythmic ?ring occurred.The
horizontal bars and corresponding numbers below the spikes indicate the spikes that were analysed for the V th and AHP properties.Only f–I relationship types 3and 4(i.e.ePIC)would include a third horizontal bar and corresponding spike numbers.B ,the ?rst two spikes from the ramp in A are shown ampli?ed.The voltage threshold was measured at the point indicated by arrow 1,the amplitude of the AHP is indicated by arrow 2(the difference between V th and AHP peak
amplitude),and the time it takes for the AHP amplitude to return to 3/4of its baseline valueis indicated by arrow 3.C ,illustration of the ?rst and last two spikes (spikes 1,18and 19)in the ramp from A .Y axis is the membrane potential,and the spikes are truncated.Spike voltage threshold and after-hyperpolarization values are listed in Table 4.
to be more frequent in slow compared to fast MNs.The presence of this ramp-induced PIC and its amplitude were not altered when the MNs were subjected to the anaesthetic mixture of ketamine and xylazine compared to the decerebrate preparation,which is used to alleviate the effects of anaesthetic.This ?nding is very signi?cant because KX allows us to estimate PICs in an intact animal (i.e.not decerebrated).
Prior to injecting ramps of current into the MN,we recorded passive properties that have been reported previously (Beaumont &Gardiner,2002,2003).Similar to the previous data that were recorded from MNs in anaesthetized animals,no signi?cant differences existed between the passive properties of fast and slow MNs (RMP and V th ),whereas slow MNs had a signi?cantly lower rheobase current.Furthermore,input resistance,AHP amplitude and AHP 1/2decay time were approximately double in slow versus fast MNs.Thus,our ?ndings concerning MN passive properties are comparable to those reported in the literature.In addition,during a ramp,fast MNs required more current to initiate and stop rhythmic ?ring compared to the slow MNs.Furthermore,fast MNs had higher instantaneous ?ring frequencies at spike recruitment and derecruitment than slow MNs,which is comparable to rhythmic ?ring for fast and slow MNs in response to square-wave pulses of current (Cormery et al.2005).Similar to cat MNs (Lee &Heckman,1998b ),rheobase was correlated with instantaneous ?ring frequency at spike recruitment and derecruitment as well as the ramp currents at which spike recruitment and derecruitment ocurred.
Motoneurones could be categorized into four f–I relationship types:(1)linear;(2)adapting;(3)linear +self-sustained ?ring;and (4)acceleration.These results are consistent with those previously reported in rat sacral MNs (Bennett et al.2001).In the present experiment,f–I relationship types 1and 2did not demonstrate the pre-sence of a PIC.This may be explained by the fact that the PIC amplitude of motoneurones tends to be muscle dependent,in that motoneurones innervating the postural muscles (triceps surae)are more likely to demonstrate PICs (Hounsgaard et al.1988;Conway et al.1988),which would be advantageous for maintaining force output during postural tasks (Alaburda et al.2002).Since sciatic nerve MNs in the rat innervate several muscle groups,the MNs demonstrating f–I relationship types 1and 2in the pre-sent study may have been MNs innervating muscles that are not required to maintain postural tasks or low forces over long periods of time.
Over 50%of the MNs we recorded from demonstrated type 3and 4f–I relationships.It is within these relationship types that the speci?c PIC voltage-gated ion channels are activated (Lee &Heckman,1998b ;Hounsgaard et al.1988;Bennett et al.2001).The difference between type 3and 4f–I relationships is probably due to the voltage at which
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol573.3Frequency–current relationships of motoneurones673 Table3.Voltage threshold,AHP amplitude and AHP duration of ramp spikes
Ramp motoneurone property KX fast cells KX slow cells Decerebration fast cells P value
Ramp V th(mV)?45.1±6.1?45.5±10.6?40.5±5.2?0.007
n=9n=7n=6
Ramp AHP amplitude(mV)8.6±2.010.6±2.79.4±2.3?0.000
n=9n=7n=6?0.02 Ramp AHP3/4duration time(ms)19.9±3.341.8±19.735.9±14.9?0.000
n=9n=7n=6?0.000
Data are presented as means±1S.D.of all MNs in each group and include all f–I relationship types.?Signi?cant
difference between KX fast and slow motoneurones;?signi?cant difference between KX and decerebration fast
motoneurones.
the speci?c voltage-gated PIC channels are activated.The PIC in types3and4may be mediated through persistent Na+and L-type Ca2+channels activated prior to the start of rhythmic?ring,while the PIC in type4may also include a L-type Ca2+channel activated at a voltage threshold after the start of rhythmic?ring(Li&Bennett, 2003).Furthermore,differences in the f–I relationship between types3and4may be due to the saturation level of the L-type Ca2+channel.Type3f–I relationship may activate the calcium PIC in a graded manner,upon which additional increases in input result in minimal changes in the Ca2+PIC(i.e.it is saturated).However,during a type4 f–I relationship the calcium PIC is perhaps activated upon MN recruitment,leading to a steep increase in the?ring frequency that coincides with the secondary range of the f–I relationship.Once the Ca2+PIC is saturated,the slope of the f–I relationship is then reduced,corresponding to the tertiary range of?ring(Elbasiouny et al.2005). Even though f–I relationship types3and4 demonstrated linear and counter-clockwise relationships, respectively,their ePIC magnitude was not different. It has been reported that Na+and Ca2+PIC channels contribute approximately equally to the total PIC of the MNs(Li&Bennett,2003),so it is possible that these channels were activated equally in the type3and4f–I relationships reported here.In addition,there was no MN type-related ePIC amplitude dominance.This was not surprising,since Lee&Heckman(1998b)demonstrated that MN bistability(a property facilitated by PIC)was more pronounced in low versus high rheobase current (a characteristic of slow versus fast type MNs,respectively; see Beaumont&Gardiner,2002);however,there was no difference in the initial PIC conductance.The lack of bistability in high rheobase current MNs may be attributed to a faster inactivation of the PIC channels. Bennett et al.(2001)also showed that no difference existed in the amount of PIC between low and high rheobase current sacral–caudal MNs.It also appears that ePIC amplitude is not related to MN type,rheobase current or input resistance in rat hindlimb MNs.Hence, MNs of all sizes have the ability to produce self-sustained ?ring.Although the previous statement may be of merit, our data lend some support to a MN type difference in the proportions of MNs demonstrating f–I relationship types3and4.There is a tendency for a greater proportion of slow MNs to have a type3or4f–I relationship, which does indeed support the?ndings(Lee&Heckman, 1998b)that a greater number of smaller MNs demonstrate bistability.
It has been suggested that the f–I function which uses current injected into the soma to?re the cell does not provide a good measure of the enhancement of synaptic input by the PIC(Heckman et al.2004). However,the ramp technique which is used to determine the f–I function for a MN has been successfully used as a way to estimate or at least demonstrate activation of its PIC or a lack thereof.We injected a series of ramp currents into each MN and,unlike earlier reports, averaged all ePIC amplitudes as overall PIC.Interestingly, if the?rst ramp demonstrated f–I relationship type3 or4(i.e.PIC)all subsequent ramps in the series also Current (nA)
Voltage threshold
(mV)
AHP amplitude
(mV)
AHP decay
time (ms)
16.1
17.8
42
46
16
12
42
25
200 ms
Figure6.Each data point represents the current and voltage threshold at each spike and its AHP amplitude and AHP3/4 decay time during the subsequent interspike interval(spikes are not shown here)from the example in Fig.5A
In this ramp,spike recruitment was induced at17.4nA and spike derecruitment occurred at16.1nA.During this ramp,the MN discharged a total of19spikes(12of which occurred below the current at which spike recruitment was initiated).Voltage threshold at each spike ranged from?42.7to?46.5mV,AHP amplitude ranged from12to16mV,and the AHP3/4decay time ranged from25to
42ms.
C 2006The Authors.Journal compilation C 2006The Physiological Society
674 D.C.Button and others
J Physiol 573.3
Table 4.Voltage threshold,AHP properties and ramp current of ?rst and last two ramp spikes
Spike 1
Spike 18Spike 19Current required for spike generation (nA)17.416.416.1V th prior to spike generation (mV)?42.7?45.6?44.0AHP amplitude (mV)
16.013.414.3AHP 3/4duration time (ms)
35.0
34.6
42.0
Data represent the V th and AHP properties of the ramp spikes in Fig.5a and c .
demonstrated f–I relationship type 3or 4(i.e.PIC).These ramp-induced ePIC amplitudes were similar across the series,with low variability.This was also the case for the other two f–I relationship types.To further illustrate the presence of PIC in types 3and 4f–I relationships,we injected ramps in a MN before and after the addition of pentobarbitone.Pentobarbitone was chosen because it abolishes MN PICs (Hultborn &Kiehn,1992;Guertin &Hounsgaard,1999;Hultborn,1999).Motoneurones
of
0.20.40.60.81.01.2KX
Decerebration
e P I C A m p l i t u d e (n A )
0.511.52Input Resistance (nA)
e P I C A m p l i t u d e (n A )
Figure 7.Illustration of average ePIC and its relation to input resistance
A ,comparison of average ePIC amplitude between MNs of KX-anaesthetized and decerebrate rats.Columns represents an
average of all ePICs (type 3and 4f–I relationships only).Data points are presented as means ±1S .D .B ,relationship between input resistance and ePIC amplitude.Each data point represents one motoneurone.Correlation coef?cients were 0.5for MNs from decerebrate rats and 0.01for MNs from KX-anaesthetized rats.
animals anaesthetized with pentobarbitone still retain the ability to ?re rhythmically,since it does not seem to affect the fast persistent inward current (Na 2+PIC channel;Lee &Heckman,2000).L-Type Ca 2+channels located on MN dendrites do not appear to amplify synaptic Ia currents in pentobarbitone-anaesthetized cats compared to decerebrate cats (Lee &Heckman,2000).Thus,it is more likely that pentobarbitone may in?uence the L-type Ca 2+channels and subsequently decrease MN bistability.Similarly,our pentobarbitone-treated MN had a major decrease in ePIC amplitude to a point where its f–I relationship was almost completely converted from type 3to type 1.The ePIC was not completely reduced to zero,suggesting that perhaps some persistent inward Na +current may not have been inhibited.The MN impalement duration lasted 80min for these recordings,but we later showed that impalement time does not in?uence the ePIC amplitude or f–I relationship type of the MN.These ?ndings recon?rm that ramps evoke PICs which subsequently alter the f–I relationship of the MN.
The possibility of an AHP amplitude and duration changing throughout an individual ramp was investigated.Lower ?ring frequencies at spike derecruitment where the activated PIC is supposed to help maintain these frequencies might be partly explained by changes in the interspike interval AHP amplitude and duration.Perhaps towards the end of motor-unit discharge,a sustained subthreshold depolarization with the addition of noise may cause the MN to ?re one or more times (Matthews,1996;Kudina,1999;Gorassini et al.2002).However,this ?nding was in human motor units,and perhaps the ?uctuation in background noise and spontaneous ?ring was due to the subject’s inadequacy to control their level of voluntary contraction.It has also been suggested in cat spinal MNs that an increased AHP duration contributes to the low ?ring frequencies at spike derecruitment (Wienecke et al.2005).Our data indicate that there were no differences between V th ,AHP amplitude or AHP duration from spike to spike during a ramp for any f–I relationship type.Occasionally,the ?nal spike had a longer AHP 3/4decay time compared to the ?rst spike during a ramp which demonstrated a f–I relationship type 3and 4,but this occurred infrequently.Furthermore,the average number of spikes triggered during the ePIC was 11(not shown in Results)and,even if the ?nal spike AHP 3/4decay time was prolonged,this did not apply to the other 10spikes.A potential limitation to this ?nding was that our ramp currents were selected on the basis of only evoking 10–75spikes over a 0.5–2.5s duration (i.e.slow ?ring rate),and we acknowledge that if we used higher ramp currents the ?ring frequency would have increased and caused changes to the properties listed above (Schwindt &Crill,1982;Bennett et al.2001).However,the main purpose of these measurements was to demonstrate that additional spike generation is probably not attributable to changes in these properties but instead to the activated PIC.
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol573.3Frequency–current relationships of motoneurones675
Another purpose for our study was to determine
the effects of ketamine and xylazine on motoneurone
properties.Therefore,we also recorded MN properties
from decerebrate rats.It has been suggested recently that
anaesthetic agents may render the MN as‘sleeping’and
may mask some of its important functional properties
(Hultborn&Kiehn,1992;Guertin&Hounsgaard,1999;
Delgado-Lezama&Hounsgaard,1999;Button et al.
2005a),which are signi?cant in‘awake’MNs.Thus,it
was important to determine whether MN properties do
indeed differ in an anaesthetized versus an unanaesthetized
rat preparation.The RMP and V th in MNs of decerebrate
rats were signi?cantly depolarized compared to MNs from
KX-anaesthetized animals and required far less rheobase
current to reach that threshold.Ketamine has been shown
to increase K+permeability in synaptosomes(Okun et al.
1986)and to block voltage-gated Na+and K+channels
in super?cial dorsal horn neurones of the lumbar spinal
cord,thereby reducing their excitability(Schnoebel et al.
2005).Perhaps this also holds true for the MN.An increase
in the permeability of K+would result in a hyperpolarized
RMP in MNs of KX-anaesthetized rats compared to MNs
of decerebrate rats.This may suggest that changes in
the activation of the ion channels or a change in their
conductance that is responsible for these motoneurone
properties may occur as a result of KX.Even though the
AHP amplitude was different,AHP duration remained the
same.Ketamine has been shown inhibit large conductance
Ca2+-activated K+(BK)channels in GH3cells(Denson&
Eaton,1994).BK channel activation is dominant during
the big and fast portion of the AHP and,if inhibited
in the MN by KX,it would lead to decreased AHP
amplitude compared to MNs of decerebrate rats.Since
AHP1/2decay times were similar in MNs of decerebrate and KX-anaesthetized rats,one could speculate that the ion
channels remain open for similar periods of time,but that
fewer ion channels open.Similarly,MNs of decerebrate
rats required less current to initiate and end rhythmic
?ring and had lower instantaneous?ring frequencies at
this initiation and end period during rhythmic?ring
compared to MNs of KX-anaesthetized rats.Overall,based
on rheobase current and the amount of current required
to initiate rhythmic?ring,a KX mixture appears to render
the MN as less excitable,and so must affect the ion channels
that underlie these basic and rhythmic properties.
No difference in ePIC amplitude existed between
anaesthetized versus unanaesthetized MNs.There is no
evidence suggesting that KX affects PIC channels.Xylazine
is anα2-adrenoceptor agonist,which presumably should
not affect PIC channels,whereas ketamine is an NMDA
receptor antagonist(Liu et al.2001).Persistent inward
currents are mediated by L-type Ca2+channels which are
selectively blocked by nimodipine(Li et al.2004),so it
is not expected that KX would in?uence PIC,which is
consistent with the results seen in this study.Although NMDA receptors have a role in membrane bistability
(Hochman et al.1994)and are present in adult turtle
MNs(Guertin&Hounsgaard,1998)and neonatal rat MNs
(Hochman et al.1994;Palecek et al.1999;Hsiao et al.
2002),they have no in?uence on PIC.The decerebrate
preparation preserves the brainstem and spinal cord in an
unanaesthetized state,which does not negatively in?uence
PIC(Kiehn,1991;Kiehn&Eken,1998;Hultborn,1999;
Heckman et al.2004).Thus,ketamine or xylazine does not
affect the major PIC channels in these MNs.
We also described V th and AHP properties from the
ramp technique which,to our knowledge,have not
been reported in the literature.Similar to the case with
short orthodromic spike,the V th values for ramp spikes
were depolarized and AHP amplitudes were bigger in
MNs of decerebrate rats.Interestingly,their AHP3/4 decay time was much longer.Ketamine inhibits the small
conductance Ca2+-activated K+channel(SK2;Dreixler
et al.2000),which is responsible for the slow portion of
the AHP and practically the whole AHP during rhythmic
?ring(Miles et al.2005).Perhaps KX partly blocked the
small conductance Ca2+-activated K+channel and its
conductance in the MN,which lead to a decreased AHP
amplitude and duration compared to MNs of decerebrate
animals.The change in these AHP properties are more
than likely to be the result of a ketamine-induced change
to the SK2channel,which behaves somewhat differently
during rhythmic?ring compared to an orthodromic spike.
Lastly,the change in?ring frequency at spike
recruitment versus derecruitment(types3and4f–I
relationships only;approximately4Hz difference)during
ramp currents in our intact anaesthetized animal
preparation is comparable to that found via paired
motor-unit methods in awake rats(Gorassini et al.1999)
and humans(Gorassini et al.2002).Motor units can be
derecruited at lower frequencies than they are initially
recruited at during slow triangular muscle contractions,
muscle vibration and sinusoidal muscle stretch.The
difference in?ring frequency between recruitment and
derecruitment is thought to be provided by the intrinsic
PIC of the motoneurone.Since these frequencies are
comparable,perhaps the ePIC amplitudes found in MNs
from our intact anaesthetized rat preparation could be
used as a starting point for estimating the size of PICs in
motor units of awake rats and humans.
In conclusion,rat hindlimbα-motoneurones injected
with ramp currents can be categorized into one of
four different f–I relationship types.Two of these
f–I relationships,which were more frequent in slow
MNs,demonstrated the existence of persistent inward
current.The ePIC amplitude did not differ between
f–I relationships type3and4or between fast and slow
MNs.Although the anaesthetic mixture of ketamine and
xylazine renders the MN less excitable to initiate spike
threshold or rhythmic threshold compared to MNs of
C 2006The Authors.Journal compilation C 2006The Physiological Society
676 D.C.Button and others J Physiol573.3
decerebrate animals,it does not affect the ePIC amplitude, but only the voltage and current required to activate these channels and AHP properties during a short spike or a burst of spikes.Ramp current injections activated the PIC channels in MNs of intact animals anaesthetized by KX and decerebrate animals.This statement is supported by the following?ndings:(1)once a MN demonstrates an ePIC,all subsequent ramp currents injected into that same MN also evoke ePICs;(2)the MN f–I relationship remains the same from ramp to ramp;(3)the addition of pento-barbitone decreases the ramp ePIC,as previously shown (Guertin&Hounsgaard,1999)in turtle MNs;(4)during the ramp,the V th and AHP properties of the spikes remain unchanged;and(5)the ramp technique has been veri?ed as successful in demonstrating the PIC,as in other animal preparations(Hounsgaard et al.1988;Lee&Heckman, 1998a;Bennett et al.2001).Finally,the anaesthetic mixture of ketamine and xylazine allows us to measure PIC in intact animals,and this mixture could be administered during future planned experiments to determine how the MN ePIC is in?uenced by different physiological parameters.
References
Alaburda A,Perrier JF&Hounsgaard J(2002).Mechanisms causing plateau potentials in spinal motoneurones.Adv Exp Med Biol508,219–226.
Beaumont E&Gardiner P(2002).Effects of daily spontaneous running on the electrophysiological properties of hindlimb motoneurones in rats.J Physiol540,129–138.
Beaumont E&Gardiner PF(2003).Endurance training alters the biophysical properties of hindlimb motoneurons in rats. Muscle Nerve27,228–236.
Bennett DJ,Li Y&Siu M(2001).Plateau potentials in sacrocaudal motoneurons of chronic spinal rats,recorded in vitro.J Neurophysiol86,1955–1971.
Brownstone RM,Jordan LM,Kriellaars DJ,Noga BR& Shefchyk SJ(1992).On the regulation of repetitive?ring in lumbar motoneurones during?ctive locomotion in the cat. Exp Brain Res90,441–455.
Button DB,Gardiner KR,Marqueste T&Gardiner PF(2005a). Frequency-current relationships in anesthetized and decerebrated rat hindlimb motoneurones in situ.Program no.750.92005.Abstract Viewer/Itinerary Planner.Society for Neuroscience,Washington,DC.(Abstract).
Button DC,Gardiner K,Zhong H,Roy RR,Egerton VR& Gardiner PF(2005b).In situ frequency-current(f-I) relationships of hindlimbα-motoneurones(α-Mns)in spinal cord transected(st)and spinal cord isolated(si)rats. Can J Appl Physiol30,S15(Abstract).
Conway BA,Hultborn H,Kiehn O&Mintz I(1988).Plateau potentials inα-motoneurones induced by intravenous injection of l-DOPA and clonidine in the spinal cat.J Physiol 405,369–384.
Cormery B,Beaumont E,Csukly K&Gardiner P(2005). Hindlimb unweighting for2weeks alters physiological properties of rat hindlimb motoneurones.J Physiol568, 841–850.Cormery B,Marini JF&Gardiner PF(2000).Changes in electrophysiological properties of tibial motoneurones in the rat following4weeks of tetrodotoxin-induced paralysis. Neurosci Lett287,21–24.
Delgado-Lezama R&Hounsgaard J(1999).Adapting motoneurons for motor behavior.In Peripeheral and Spinal Mechanisms in the Neural Control of Movement,ed.Binder MD,chap.5,pp.57–63.Progress in Brain Research Vol.123, Elsevier,NY,USA.
Denson DD&Eaton DC(1994).Ketamine inhibition of large conductance Ca2+-activated K+channels is modulated by intracellular Ca2+.Am J Physiol267,C1452–C1458. Dreixler JC,Jenkins A,Cao YJ,Roizen JD&Houamed KM (2000).Patch-clamp analysis of anesthetic interactions with recombinant SK2subtype neuronal calcium-activated potassium channels.Anesth Analg90,727–732. Elbasiouny SM,Bennett DJ&Mushahwar VK(2005). Simulation of Ca2+persistent inward currents in spinal motoneurons:mode of activation and integration of synaptic inputs.J Physiol570,355–374.
Fouad K&Bennett DJ(1998).Decerebration by global ischemic stroke in rats.J Neurosci Meth84,131–137. Gardiner PF(1993).Physiological properties of motoneurons innervating different muscle unit types in rat gastrocnemius. J Neurophysiol69,1160–1170.
Gardiner PF&Seburn KL(1997).The effects of tetrodotoxin-induced muscle paralysis on the physiological properties of muscle units and their innervating motoneurons in rat.
J Physiol499,207–216.
Gilmore J&Fedirchuk B(2004).The excitability of lumbar motoneurones in the neonatal rat is increased by a hyperpolarization of their voltage threshold for activation by descending serotonergic?bres.J Physiol558,213–224. Gorassini M,Bennett DJ,Kiehn O,Eken T&Hultborn H (1999).Activation patterns of hindlimb motor units in the awake rat and their relation to motoneuron intrinsic properties.J Neurophysiol82,709–717.
Gorassini M,Yang JF,Siu M&Bennett DJ(2002).Intrinsic activation of human motoneurons:possible contribution to motor unit excitation.J Neurophysiol87,1850–1858. Granit R,Kernell D&Shortess GK(1963).Quantitative aspects of repetitive?ring of mammalian motoneurones,caused by injected currents.J Physiol168,911–931.
Guertin PA&Hounsgaard J(1998).NMDA-Induced intrinsic voltage oscillations depend on L-type calcium channels in spinal motoneurons of adult turtles.J Neurophysiol80, 3380–3382.
Guertin PA&Hounsgaard J(1999).Non-volatile general anaesthetics reduce spinal activity by suppressing plateau potentials.Neuroscience88,353–358.
Heckman CJ,Gorassini MA&Bennett DJ(2004).Persistent inward currents in motoneuron dendrites:implications for motor output.Muscle Nerve31(2),135–156.
Hochman S,Jordan LM&Schmidt BJ(1994).TTX-resistant NMDA receptor-mediated voltage oscillations in mammalian lumbar motoneurons.J Neurophysiol72,
2559–2562.
Hounsgaard J,Hultborn H,Jespersen B&Kiehn O(1988). Bistability ofα-motoneurones in the decerebrate cat and in the acute spinal cat after intravenous5-hydroxytryptophan. J Physiol405,345–367.
C 2006The Authors.Journal compilation C 2006The Physiological Society
J Physiol573.3Frequency–current relationships of motoneurones677
Hsiao CF,Wu N,Levine MS&Chandler SH(2002). Development and serotonergic modulation of NMDA bursting in rat trigeminal motoneurons.J Neurophysiol87, 1318–1328.
Hultborn H(1999).Plateau potentials and their role in regulating motoneuronal?ring.Prog Brain Res123,39–48. Hultborn H&Kiehn O(1992).Neuromodulation of vertebrate motor neuron membrane properties.Curr Opin Neurobiol2, 770–775.
Kernell D(1965a).The adaptation and the relation between discharge frequency and current strength of cat lumbosacral motoneurones stimulated by long-lasting injected currents. Acta Physiol Scand65,65–73.
Kernell D(1965b).High-frequency repetitive?ring of cat lumbosacral motoneurones stimulated by long-lasting injected currents.Acta Physiol Scand65,74–86.
Kernell D(1965c).The limits of?ring frequency in cat lumbosacral motoneurones possessing different time course of afterhyperpolarization.Acta Physiol Scand65,87–100. Kernell D&Monster AW(1981).Threshold current for repetitive impulse?ring in motoneurones innervating muscle?bres of different fatigue sensitivity in the cat.Brain Res229,193–196.
Kiehn O(1991).Plateau potentials and active integration in the ‘?nal common pathway’for motor behaviour.Trends Neurosci14,68–73.
Kiehn O&Eken T(1998).Functional role of plateau potentials in vertebrate motor neurons.Curr Opin Neurobiol8,
746–752.
Kudina LP(1999).Analysis of?ring behaviour of human motoneurones within‘subprimary range’.J Physiol(Paris) 93,115–123.
Lee RH&Heckman CJ(1998a).Bistability in spinal motoneurons in vivo:systematic variations in rhythmic
?ring patterns.J Neurophysiol80,572–582.
Lee RH&Heckman CJ(1998b).Bistability in spinal motoneurons in vivo:systematic variations in persistent inward currents.J Neurophysiol80,583–593.
Lee RH&Heckman CJ(1999).Paradoxical effect of QX-314on persistent inward currents and bistable behavior in spinal motoneurons in vivo.J Neurophysiol82,2518–2527.
Lee RH&Heckman CJ(2000).Adjustable ampli?cation of synaptic input in the dendrites of spinal motoneurons in vivo.J Neurosci20,6734–6740.
Li Y&Bennett DJ(2003).Persistent sodium and calcium currents cause plateau potentials in motoneurons of chronic spinal rats.J Neurophysiol90,857–869.
Li Y,Gorassini MA&Bennett DJ(2004).Role of persistent sodium and calcium currents in motoneuron?ring and spasticity in chronic spinal rats.J Neurophysiol91,767–783. Liu HT,Hollmann MW,Liu WH,Hoenemann CW&Durieux ME(2001).Modulation of NMDA receptor function by ketamine and magnesium:Part I.Anesth Analg92,
1173–1181.
Matthews PB(1996).Relationship of?ring intervals of human motor units to the trajectory of post-spike after-hyperpolarization and synaptic noise.J Physiol492,597–628. Miles GB,Dai Y&Brownstone RM(2005).Mechanisms underlying the early phase of spike frequency adaptation in mouse spinal motoneurones.J Physiol566,519–532.Munson JB,Foehring RC,Mendell LM&Gordon T(1997). Fast-to-slow conversion following chronic low-frequency activation of medial gastrocnemius muscle in cats.
II.Motoneuron properties.J Neurophysiol77,2605–2615. Okun IM,Aksentsev SL&Konev SV(1986).Effect of the general anesthetic ketamine on the potassium permeability of plasma membranes of brain synaptosomes.[In Russian] Bio?zika31,917–918.
Palecek JI,Abdrachmanova G,Vlachova V&Vyklick L(1999). Properties of NMDA receptors in rat spinal cord motoneurons.Eur J Neurosci11,827–836.
Powers RK&Binder MD(2001).Input-output functions of mammalian motoneurons.Rev Physiol Biochem Pharmacol 143,137–263.
Powers RK,Sawczuk A,Musick JR&Binder MD(1999). Multiple mechanisms of spike-frequency adaptation in motoneurones.J Physiol(Paris)93,101–114.
Sawczuk A,Powers RK&Binder MD(1995).Spike frequency adaptation studied in hypoglossal motoneurons of the rat. J Neurophysiol73,1799–1810.
Schnoebel R,Wolff M,Peters SC,Brau ME,Scholz A, Hempelmann G,Olschewski H&Olschewski A(2005). Ketamine impairs excitability in super?cial dorsal horn neurones by blocking sodium and voltage-gated potassium currents.Br J Pharmacol146,826–833.
Schwindt PC(1973).Membrane-potential trajectories underlying motoneuron rhythmic?ring at high rates.
J Neurophysiol36,434–439.
Schwindt P&Crill WE(1977).A persistent negative resistance in cat lumbar motoneurons.Brain Res120,173–178. Schwindt PC&Crill WE(1981).Negative slope conductance at large depolarizations in cat spinal motoneurons.Brain Res 207,471–475.
Schwindt PC&Crill WE(1982).Factors in?uencing motoneuron rhythmic?ring:results from a voltage-clamp study.J Neurophysiol48,875–890.
Skydsgaard M&Hounsgaard J(1996).Multiple actions of iontophoretically applied serotonin on motorneurones in the turtle spinal cord in vitro.Acta Physiol Scand158,301–310. Wienecke J,Zhang M&Hultborn H(2005).The postspike afterhyperpolarization(AHP)following single spikes is prolonged by a preceding spike-train in cat spinal motneurones.Program no.750.8.Viewer/Itinerary Planner. Society for Neuroscience,Washington,DC,USA.(Abstract). Zengel JE,Reid SA,Sypert GW&Munson JB(1985). Membrane electrical properties and prediction of motor-unit type of medial gastrocnemius motoneurons in the cat. J Neurophysiol53,1323–1344.
Acknowledgements
This research was supported by grants from NSERC Canada, CIHR,and the Canada Research Chairs program.The authors would like to thank Gilles Detillieux,Matt Ellis and Maria Setterbom at University of Manitoba for technical assistance, Farrell Cahill for assistance in data analysis,and Dr Jayne Kalmar for comments and suggestions during manuscript preparation. P.F.G.is Canada Research Chair in Physical Activity&Health Studies at University of Manitoba.
C 2006The Authors.Journal compilation C 2006The Physiological Society
口吃自我治疗心得
我的口吃纠正法——演故事 作者执立 我的确没有去过什么口吃矫正学校，我的口吃的治愈，说出来，可能你不信，除去周围朋友的督导，最大的秘密就是熟读《庄子》和部分心理学方面的书籍！当然一些必要的语言训练是要有的，我最喜欢的训练是，演故事！就是先熟悉一个故事，然后自己静静的讲出来。然后再讲给别人听。然后再让别人在我讲故事的时候，向我提问，这样就把自己单纯的讲故事变成了对话！最后就开始演故事，那就是要配合好自己的语气、语速、语调、节奏、乃至肢体语言还有面部的表情！最好选择一个长度适中的笑话故事，看你演完后是不是会笑到一大片！如果效果很好，那么我告诉你，你离纠正口吃就不远了纠正好自己的口吃以后，我一直在研究口吃！我认为，之所以出现那么多口吃矫正班的学员毕业后重新又口吃，我就开始注意到了口吃风格的问题！我认为，引起口吃的原因不一样，当然治疗的方法也就会不一样的！但是所有的口吃矫正的最后一步肯定是一样的，那就是纠正长期口吃的习惯！风格不同的口吃，纠正的前一阶段肯定是不同的，有的人因为惊吓的了口吃，并且时间特别短，那么治疗饿方法重点是消除惊吓带来的心理障碍或者是情景性障碍！而对这样的口吃患者进行发音法和拖音法或者呼吸法的训练肯定没有用！如果一个人同样由于受惊吓而得了口吃，但是时间很长了，那么在消除，口吃患者的心理障碍的情况下，还要做相应的发音法方面的训练，因为，由于他长期的不正确发音习惯，导致了他说话的候发音器官的不协调，发音法可以调节好这一些的！相传古希腊的一个演讲家，口含石子，对着大海朗诵，最终改变了口吃，其实这就是一种发音法的治疗！因为口含石子说话时，发音器官的活动与平日说话是不一样的，也就是说，口含石子，其目的在于创造一种全新的说话模式！ 我口吃纠正的路子是，第一步培养自己浩大的人格，自卑的怯懦的人容易口吃，如果你有孟子的浩然之气，你有庄子那样与天地精神独往来的胸怀，你口吃会大为减少！第二步，是培养一种从容的舒缓的性格，我建议大家每做一件事情都要能够等一分钟，或者是慢半拍，最好训练方式，我建议是练习书法，一笔一划的写字，写上两个月，肯定会有改变！第三步，才是纠正口吃，弄一些发音法啊，呼吸法啊等等！正所谓，功夫在诗外，前两步非常重要！ 至于说到的我为什么不做口吃纠正师，我想每个人做事情都有轻重缓急之分！我目前的目标是想在自己最喜欢的大学把博士学位拿到！以后如果有机会一定会涉足这个领域！现在有很多吃友想让我办班，我都是以我的矫正费很贵为搪塞来推辞的，因为我要纠正的话，我一次最多接受两个人，在三个月内我要为之竭尽心血！并且三个月以后，我还有做好之后的服务！又加之自己的学习与事业正在转型时期，不能过多分散精力！我在空间里面有声明，不聊天，只在有时间的时候回复吃友的留言！现在已经有多名吃友按照我的要求去做，并且取得了可观的效果！ 为什么与陌生人说话反而不可吃执立撰 刻意，会很好的缓解口吃，那样你会自觉的放慢自己的语速，甚至会调整自己的语气、语调！ 有很多人询问我说，他们与陌生人说话反而不口吃，但是一旦说话的时间过长，逐渐熟悉就会慢慢的口吃！或者是与熟悉的人说话就很口吃！ 我认为，你在与陌生的人说话的时候，你具备了两个基本的缓解口吃的条件！第一，你改变了以往的那种你熟悉的口吃的语言环境，因为他不知道你有口吃，你在与陌生人接触的时候，没有口吃带来的压力和恐惧！也就是我所说的，你抽离了那种让你口吃的语言
频数分布图的做法(函数法).
实例用数组公式： FREQUENCY 以一列垂直数组返回某个区域中数据的频率分布。例如，使用函数FREQUENCY 可以计算在给定的分数范围内测验分数的个数。由于函数FREQUENCY 返回一个数组，所以必须以数组公式的形式输入。 语法 FREQUENCY(data_array,bins_array) Data_array 为一数组或对一组数值的引用，用来计算频率。如果data_array 中不包含任何数值，函数FREQUENCY 返回零数组。（注：就是你想看分布的那些原始数据） Bins_array 为间隔的数组或对间隔的引用，该间隔用于对data_array 中的数值进行分组。如果bins_array 中不包含任何数值，函数FREQUENCY 返回data_array 中元素的个数。（注：就是你想用来分原始数据档的那些序列数，这个要自己根据需要先做好，备用） 说明 在选定相邻单元格区域（该区域用于显示返回的分布结果）后，函数FREQUENCY 应以数组公式的形式输入。 返回的数组中的元素个数比bins_array（数组）中的元素个数多1。返回的数组中所多出来的元素表示超出最高间隔的数值个数。例如，如果要计算输入到三个单元格中的三个数值区间（间隔），请一定在四个单元格中输入FREQUENCY 函数计算的结果。多出来的单元格将返回data_array 中大于第三个间隔值的数值个数。 函数FREQUENCY 将忽略空白单元格和文本。 对于返回结果为数组的公式，必须以数组公式的形式输入。 示例 本示例假设所有测验分数都为整数。 如果您将示例复制到空白工作表中，可能会更易于理解该示例。 操作方法 创建空白工作簿或工作表。 分数分段点 79 70 85 79 78 89 85 50 81 95 88 97 注：分数那一列拷贝到从A2-A10的部分，分段点列拷贝到B2-B5 公式说明（结果） =FREQUENCY(A2:A10,B2:B5) 分数小于等于70 的个数(1) 成绩介于71-79 之间的个数(2) 成绩介于80-89 之间的个数(4) 成绩大于等于90 的个数(2) 注释示例中的公式必须以数组公式的形式输入。将示例复制到空白工作表之后，请选中从公式单元格开始的单元格区域 A13:A16。按 F2，再按 Ctrl+Shift+Enter。如果公式未以数组公式的形式输入，则
浅谈幼儿口吃
浅谈幼儿口吃 口吃是语音节律障碍的一种，是由于不同原因引起字音重复或语流中断的语音节律障碍。当语言表达阻塞时常伴躯体抽搐样动作和面部异常那个的表情。口吃多发于儿童，一般随着年龄的增长逐渐改善或者消失，很少有延续到成年的。 幼儿口吃的原因有很多，3~4岁的孩子认识的事物已经很多，但掌握的词汇较少，而且不牢固。迫切地想表达自己的意思，一下子又找不到适当的词汇，再加上发音器官尚未发育成熟，对某些发音会感到困难，而且神经系统调节言语的功能又差，也就容易形成口吃。模仿和暗示也是很大的一个原因，大部分口吃患者是在幼小时学别人的口吃学来的，儿童期是学习和掌握语言的关键期，儿童的心里特点之一是模仿性强和易受暗示，当亲友、同学、邻居中如果有口吃的人就很可能会成为幼儿的模仿对象。其次是心理因素，幼儿口吃很可能是儿童受惊、被严厉斥责、嘲笑、惩罚、环境突然发生变化或者父母离异、双亡或家庭不和睦等情境下引起的恐惧、焦虑情绪的结果。在一些突然震惊恐惧的事件后可发生口吃，有可能在受惊恐的当时发生，也有可能在受惊恐之后的几小时或几天之后才出现，有时是经过沉默后才出现的。幼儿的口吃还有可能是同伴太善辩，使他想说而没有机会说造成的。还有可能是疾病引起的，如与发音、对语言理解甚至读书写字有密切关系的神经系统发生障碍;如小儿癫痫、麻疹、热病、脑病、百日咳、猩红热、脓症、鼻炎、扁桃腺发炎或肥大等等，以及耳鼻喉科的疾病，多少都能使呼吸和发声受到影响。当然还有可能是遗传导致的。总之，幼儿口吃的原因是多种多样的，我们要根据发生的原因来防止。 没有口吃我们要如何“防”呢？有口吃我们又要如何“治”呢？ 针对“防”，首先，肯定是要为幼儿营造一个愉快宽松的生活氛围，让孩子心平气和地讲话。其次，杜绝幼儿模仿口吃患者，如果身边有这样的口吃患者与幼儿接触，一定要清楚地告诉幼儿，不能模仿他们说话，并告诉他们模仿他们讲话是不礼貌的，而且以后自己也会变成口吃。第三，安排好幼儿的日常生活和培养良好的卫生习惯，儿童的日常生活要有规律，保证足够的睡眠和休息。大人不要强迫3~7岁的儿童牢记各种长篇故事或不适应他们语言能力的诗歌。 针对“治”，关键是要培养幼儿良好的讲话习惯，其父母、老师应耐心教导，告诉他怎样把话讲清楚，如何正确表达自己的意思。如果他讲对了，一定要鼓励他“讲得好”，以此来帮助他树立学习掌握讲话技巧的信心。当他讲话不清楚或不流畅，也要耐心听完，不要打断或随意责骂，不能造成精神紧张，一说话就紧张。 查阅资料后我还发现，音乐在矫正儿童口吃方面发挥良好的作用。有节奏的唱歌、朗诵对儿童语言训练有一定的帮助，儿童听了音乐指挥，因心情愉快，分散说话时的注意力，这样能使儿童容易讲出自己要说的话。讲故事也是帮助儿童矫正口吃的一种方法。家长可以让孩子讲诉幼儿园的事情；与孩子对话，讲看的新书、新电视剧。当然，在这些过程中家长一定要有耐心。需要注意的是每次的时间不要太长，时间长了会让幼儿感到精神疲倦，一般20~30分钟即可。 幼儿口吃是需要我们重视的一个问题，对于将来要做幼儿教师的我们更要多去了解，多去探索一些有用的方法来帮助和关心身边这样的孩子。
在Excel中使用FREQUENCY函数统计各分数段人数
在Excel中使用FREQUENCY函数统计各分数段人数 用Excel怎样统计出学生成绩各分数段内的人数分布呢？很多文章都推荐使用CountIF 函数，可是每统计一个分数段都要写一条函数，十分麻烦。例如，要在C58:C62内统计显示C2:C56内小于60分、60至70之间、70至80之间、80至90之间、90至100之间的分数段内人数分布情况，要输入以下5条公式： 1. 在C58内输入公式统计少于60分的人数：=CountIF(C2:C56,"<60") 2. 在C59内输入公式统计90分至100之间的人数：=CountIF(C2:C56,">=90") 3. 在C60内输入公式统计80至90之间的人数：=CountIF(C2:C56,">=80")-CountIF(C2:C56,">=90")， 4. 在C61内输入公式统计70到80之间的人数：=CountIF(C2:C56,">=70")-CountIF(C2:C56,">=80")， 5. 在C62内输入公式统计60到70之间的人数：=CountIF(C2:C56,">=60")-CountIF(C2:C56,">=70")。 如果要把0至10之间、10至20之间、20至30……90至100之间这么多个分数段都统计出来，就要写上十条公式了。可见用COUNTIF()函数效率并不高。 其实，Excel已经为我们提供了一个进行频度分析的FreQuency数组函数，它能让我们用一条数组公式就轻松地统计出各分数段的人数分布。 FREQUENCY函数说明如下: -------------------------------------------------- 语法： FREQUENCY(data_array,bins_array) 参数: data_array:需要进行频率统计的一组数。 bins_array:为间隔的数组，该间隔用于对data_array中的数值进行分组。 返回值: 以一列垂直数组返回某个区域中数据的频率分布。例如，使用函数FREQUENCY 可以计算在给定的分数范围内测验分数的个数。 注: 1、返回的数组中的元素个数比bins_array（数组）中的元素个数多1。所多出来的元素表示超出最高间隔的数值个数。 2、由于返回结果为数组，必须以数组公式的形式输入。即给定FREQUENCY的参数
失眠症及其治疗方法
失眠症及其治疗方法 失眠症及其治疗方法 失眠症在中医里叫不寐。亦称不得眠、不得卧、目不瞑。是指经常不能获得正常睡眠为特征的一种病证。失眠症的症状轻重不一，轻者有入睡困难，有眠而易醒，有醒后不能再睡，亦有时睡时醒，还有虽睡却多梦等，严重者则整夜不能入睡。失眠症亦可单独出现，也可与头痛、眩晕、心悸、健忘等同时出现。 早在《素问·逆调论篇》中，就有黄帝问歧伯为什么有人不得卧，歧伯解释说：“胃不和则卧不安”。《黄帝内经·灵枢》中黄帝又就不得卧先后请教伯高和歧伯。伯高认为，阴虚者不得卧，治宜补其不足，泻其有余调和虚实，勾通阴阳，再服半夏汤一剂，便能安然入睡了。歧伯则认为不得卧是由于阳气盛，阴气虚，见地与伯高相近。由此可见早在两千多年以前，古人对失眠症的研究已达到相当高的水平。 今人与古人相比，受失眠症伤害的更普遍，更广泛，也更严重。 按说，“三十年前睡不醒”。在传统的农业社会里，生活的节奏是如此缓慢，当人们把爷辈的成功经验一成不变地传给孙辈的时候，如若孙辈效而行之，成功率仍然是很高的。与之相反，人们可以在现实生活中找到许许多多严酷而惨痛的事
实，告诫自己的孩子：“不听老人言，吃苦在眼前。”更何况孔夫子也说“三十而立”既然孔圣人到了三十岁才走向自立，那么三十岁以前依赖父母，听从父母就行了，自己无须操心，自然也就睡不醒了。 而今的青年人就不行了。因为从他能看能说开始，至少有百分之九十的信息不是来自他的父母，他自小就必须自立去判断选择。现实的生活是，那些自小依赖性很强的孩子最容易受到生活的伤害。据我临床发现，也是众所周知的事实，在大中学生中受失眠症伤害也是非常普通，非常广泛，非常严重的。 导致失眠症的原因很多。但主要包括两个方面的原因：一是心理方面的原因，二是生理方面的原因。失眠症多为情绪所困，具体说，入睡困难是由于焦虑所致，醒后不能再眠是因抑郁所伤。至于生理方面的原因，一般情况下，你很难用现代医学检测的方法及设备把它查出来，也很难用现代医学的语言把它描述清楚。这里，只能用中医的诊断方法及语言把它描述出来：即思虑劳倦，内伤心脾，阳不交阴，心肾不交，阴虚火旺，肝阳扰动，心胆气虚以及胃中不和等因素，均可影响心神而导致失眠症。中医辨证论治，又有虚证、实证之分。而青年人的失眠症大多属于虚证。 失眠症治疗的方法不少。这里，我向你介绍几种简便易行而又经临床反复验证是卓有成效的方法。
儿童口吃的原因及矫正方法
儿童口吃的原因及矫正 方法 集团文件版本号：（M928-T898-M248-WU2669-I2896-DQ586-M1988）
儿童口吃的原因及矫正方法孩子成长的过程中，有些家长会发现，明明说话说得很好的孩子，突然之间变得口吃了。很多家长焦急万分：家里明明没有口吃的遗传，周围也没有人是口吃，这种情况是怎么造成的呢？ 口吃的原因 1、遗传因素：口吃患者家族发病率可达36%～55%，故有人认为与遗传因素有关，可能为单基因遗传。有人发现的孩子口吃是有家族遗传史，主要外因是学习语言的环境不佳，如父母口吃，或父母口语快、含混，儿童不易模仿等。也有人发现口吃患者及亲属中左利手多见，认为口吃与大脑优势侧有关。 2、精神因素：儿童口吃往往发生在急性或迁延性精神创伤之后，因而不少学说认为精神因素可能为口吃的重要发病原因。有的儿童因为受到家长、老师或周围一些人的严厉惩罚或训斥，使精神突然受到严重打击，由于这种恐惧的情绪或惊吓引起了口吃，同时精神紧张、焦虑等也会导致口吃现象。 3、躯体因素：先天的发育不良也引起口吃。较多儿童围产期或婴幼儿期曾受到有害因素作用，如胎儿期母体患妊娠毒血症、出血或躯体性疾病，或发育过程中患某些传染病使神经系统功能弱化，言语功能受累而致口吃。 4、外界因素：强行纠正左撇子也会造成口吃。 5、方言性口吃：儿童学语期间改变方言，或兼学两种以上不同方言，可致口吃。
6、思维过速性口吃：因思路宽阔迅速，致使口齿追随不及，造成口吃。临床亦较常见。 7、其它因素：有的学龄前儿童罹患口吃是因模仿所致。有资料则根据脑电图、发音肌肌电图和氟哌啶醇临床疗效。推断口吃可能与边缘系统和网状结构复合体活动增强、发音肌功能不协调、和基底节存在生化障碍等因素有关，但尚待临床进一步论证。 口吃的表现形式 口吃的表现形式很多样，医学上通常把它分为三大类：首字难发型、语词重复型、语句中断型。而96%的口吃表现为首字难发。多数患儿初期仅有言语症状，部分严重患者可有唇、下颌、颈部肌肉痉挛、舌肌震颤、跺脚、眨眼、转头等因生理紧张而产生的各种伴随动作。此时，父母的态度、社交受挫、精神压力等因素可促使口吃不断加重及伴随动作增多。 1、首字难发型：表现为第一字发音时发不出，第一字重复，话语中途某字发音障碍; 2、语词重复型：经常出现语音或音节的重复或延长，影响说话的流畅性; 3、无表达内容障碍;因发音-呼吸器官的紧张性痉挛，导致语言节奏失调 4、排除抽动症及其他神经系统疾病。患儿说话时，可伴有跺脚、摆手、挤眼、歪嘴、口唇颤抖、躯干摇晃等动作。部分患儿常易兴奋或激惹，并伴有情绪不稳和睡眠障碍等。
Excel表格中的一些基本函数使用方法
Excel表格中的一些基本函数使用方法 一、输入三个“=”，回车，得到一条双直线； 二、输入三个“~”，回车，得到一条波浪线； 三、输入三个“*”或“-”或“#”，回车，惊喜多多； 在单元格内输入=now（）显示日期 在单元格内输入=CHOOSE(WEEKDAY(I3,2),"星期一","星期二","星期三","星期四","星期五","星期六","星期日") 显示星期几 Excel常用函数大全 1、ABS函数 函数名称：ABS 主要功能：求出相应数字的绝对值。 使用格式：ABS(number) 参数说明：number代表需要求绝对值的数值或引用的单元格。 应用举例：如果在B2单元格中输入公式：=ABS(A2)，则在A2单元格中无论输入正数（如100）还是负数（如-100），B2中均显示出正数（如100）。 特别提醒：如果number参数不是数值，而是一些字符（如A等），则B2中返回错误值“#VALUE！”。 2、AND函数 函数名称：AND 主要功能：返回逻辑值：如果所有参数值均为逻辑“真（TRUE）”，则返回逻辑“真（TRUE）”，反之返回逻辑“假（FALSE）”。
使用格式：AND(logical1,logical2, ...) 参数说明：Logical1,Logical2,Logical3……：表示待测试的条件值或表达式，最多这30个。 应用举例：在C5单元格输入公式：=AND(A5>=60,B5>=60)，确认。如果C5中返回TRUE，说明A5和B5中的数值均大于等于60，如果返回FALSE，说明A5和B5中的数值至少有一个小于60。 特别提醒：如果指定的逻辑条件参数中包含非逻辑值时，则函数返回错误值“#VALUE!”或“#NAME”。 3、AVERAGE函数 函数名称：AVERAGE 主要功能：求出所有参数的算术平均值。 使用格式：AVERAGE(number1,number2,……) 参数说明：number1,number2,……：需要求平均值的数值或引用单元格（区域），参数不超过30个。 应用举例：在B8单元格中输入公式： =AVERAGE(B7:D7,F7:H7,7,8)，确认后，即可求出B7至D7区域、F7至H7区域中的数值和7、8的平均值。 特别提醒：如果引用区域中包含“0”值单元格，则计算在内；如果引用区域中包含空白或字符单元格，则不计算在内。 4、COLUMN 函数 函数名称：COLUMN 主要功能：显示所引用单元格的列标号值。
面对口吃儿童的教学设计
篇一：儿童口吃案例2 他逐渐克服了表达困挠 案例介绍 包某，男，10岁，某小学四(3)班学生。学习成绩一般，消瘦，家庭生活宽裕，深得父母的宠爱，爱撒娇。性格外向，情绪不稳定，好动，不能很好的约束自己的行为，爱思考问题，表现欲强，发言积极，可说话时却有语言表达障碍，让人听起来很费劲，严重影响了语言表达。 案例分析 母亲生产包某时属早产，因此从小体质较弱，常生病。在学说话期间，由奶奶带着。奶奶教包某说话的时候字音过重，尾音拖得过长，如“吃——饭”，久而久之造成了说话字音长，重复次数较多的现象。辅导方法 1、创造良好的心理环境。口吃的形成、加重，与患儿和周围人的态度有关，因此，教师首先向包某以及其家长和同学讲述口吃的性质与成因，建议家长和学生们尊重包某人格，不嘲笑戏弄他，耐心听包某讲话，不当面议论其病态，并且在与包某讲话时保持心平气和、不慌不忙，使其受到感化，而养成从容不迫的讲话习惯。包某口吃严重时，不强求其讲话，以避免紧张。 2、不断鼓励，树立信心。充满信心，便迈开了战胜困难的第一步。教师首先通过有关英国前首相邱吉尔努力战胜口吃，成为著名政治家的故事，让包某树立榜样，并认识到口吃是可以战胜的。其次，组织全班学生给包某送一句赠言，以此鼓励其战胜困难的决心。再次， 关注包某的每一点进步，并及时通过语言、动作、笑容给予肯定，树立其战胜口吃的信心，培养沉着开朗的性格。此外，还鼓励包某积极参加社会活动和人际交往，减轻由口吃产生的神经质和心理障碍。 3、进行系统的语言训练治疗。教师首先让包某在没人的环境，从容地练习发音，先念单词，再练短句，再读长句。有时还配合音乐、动作、节拍从容不迫地、有节奏地练习讲话、背诵文章段落。在家里，让包某收听广播或电视，模仿播音员朗读，逐渐克服口吃，说话流畅。就这样，由近及远地与他人说话，最后再上讲台讲话。 在训练过程中教与放松情绪和肌肉的说话方法，通过安抚减少焦虑，有助于语言训练的成功。对于讲话出现口吃现象时不予理睬；而讲话无口吃时，给予适当的赞扬或鼓励。逐渐增加讲话速度和提高流利程度要求，每有进步，均给予表扬。 辅导效果 经过系统的训练，包某终于克服了语言表达障碍，不存在有字音重复，尾音拖长的现象，人比以前更自信，更关心热爱班级体了。 篇二：儿科学辅导：儿童口吃预防措施 为了防止儿童口吃，安排好儿童的日常生活和培养良好的卫生习惯是很重要的。儿童日常的生活要有规律，要按照规定的时间吃饭，保证足够的睡眠和休息。不要强迫3～7岁的儿童牢记各种长篇故事或不适应他们语言能力的诗歌。 矫正儿童口吃的关键是要培养一个良好的讲话习惯。对于患口吃的儿童，父母、老师应耐心教导，告诉他怎样把话讲清楚，如何正确表达自己的意思。如果他讲对了，就要鼓励他“讲得好”，帮助他树立学习掌握讲话技巧的信心。如果他讲话不清楚或不流畅，也要耐心听完，不要中途打断或随意责骂，使孩子以后在人前不敢讲话，或造成精神紧张，一说话就口吃。音乐可以在矫正儿童口吃方面发挥良好的作用。有节奏的唱歌、朗诵对儿童语言训练有一定的帮助，儿童听了音乐之后，因心情愉快，分散说话时的注意力，不是仅关注讲话的动作，这样，就能使儿童容易讲出自己要说的话。讲故事也是帮助儿童矫正口吃的一种方法。家长可以让孩子叙述幼儿园、学校里的事情；与孩子对话，讲看的新书、新电视剧。需要注意的
excel函数学习教程可资借鉴的学习步骤(精)
函数学习教程可资借鉴的学习步骤 第一部分:函数与公式基础 第1集:公式与运算符 什么是公式?函数?怎么在EXCEL里进行计算?如果你和我当初一样菜,那就老老实实的从这一集学起吧。认识一下公式的种类、学习使用加减乘除、乘方、开方等运算符。 第2集:相对引用与绝对引用 为什么公式复制时A1会变成A2,公式拖动时能不能不变化呢?可有时。。。又需要变化。这个。。怎么才能让它变就变,不让它变就老实的呆着呢?学会引用方式,A1的72变就逃不出你的手心了。 第3集:公式的调试与操作技巧 公式常出错、咋快速找出错误?合并单元格大小不一,怎么复制?公式怎么隐藏起来?可恶的“不能更改数组的一部分”提示,不让我更改公式。掌握公式的调试与操作技巧,是你学习函数公式前必须打好的基础。 第二部分:逻辑与判断函数 第4集:IF函数 单条件、混合条件、多条件、区间条件的判断,IF很给力,配合AND和OR两个小助手,这些都可以帮你实现。 第5集:信息类函数 ISODD判断奇偶、ISNUMBER判断数字、ISTEXT判断文本、ISERROR判断错误值、实在不行还有TYPE函数。日期与数学竟然也可以用CELL函数判断。还有什么不能判断的?
第三部分:计数、求和及数学函数 第6集:COUNT和COUNTA函数 在EXCEL函数里,简单总是相对的,这两个函数简单不?简单,难不?难!想真正的灵活应用,还真要需要一些实战经验。本集除了介绍几个小应用,也给大家提供一个在数组公式中应用的实例。为学习函数数组打打基础。 第7集:SUM函数 会用EXCEL的同学,都会用这个函数。你用过可以多表合并的SUM吗?你会用它巧设含有数个小计的累计数吗?还是那句话,函数简单,学会灵活应用还是需要下点功夫的。 第8集:COUNTIF函数 每次给企业培训,这个函数总是会重点推荐,因为它太。。。太重要了,看看它可以实现的功能你会不会已对它垂涎欲滴。两个表格核对、提取唯一值、删除重复的行、防止重复录入、限制录入的内容、根据条件统计个数..它的作用真是罄竹难书。。。。 第9集:SUMIF函数 SUMIF你会了,根据条件求和你会吗?曾经菜鸟时的我,学会了这个函数几近疯狂。它竟然可以帮我自动实现了供货商的往来账的自动汇总,不用再一个个的手工加了。那个激动啊.....别笑我,那时我就是这么的菜.... 第10集:SUMPRODUCT函数 萨达姆不绕打他的,这个函数真让我无语。你你怎么可以这样,即可以多条件计数、又可以多条件求和,竟然还可以多条件模糊求和。这让自诩功能强大的COUNTIF和SUMIF函数情何以堪啊....
失眠症的合理用药及其治疗方案分析
失眠症的合理用药及其治疗方案分析
失眠症的起因、合理用药及其治疗方案分析 杜江旷石 （湖南省株洲市三医院，株洲41200） 【摘要】失眠症是现代社会强压力下的一种常见临床症状，绝大一部分已经影响到人类的身体健康和正常生活。失眠症一定要对因治疗，综合治疗，药物治疗和心理治疗并进，这样才能从根本上解决失眠问题，从而更健康美好的生活。本文主要讲述的是怎样合理的使用镇静催眠药物并合并其他辅助药物使用，在此同时加以心理辅导，穴位按摩等，并制定合理的治疗方案来解决失眠者的烦恼，让他们能有一个美妙的睡眠。 【关键词】：入睡和睡眠障碍；合理用药；镇静催眠药；心理治疗Causes of insomnia, rational drug and treatment program analysis Du Jiang Kuang Shi （The third people's Hospital of Zhuzhou city Hunan Province，zhuzhou 412000） [Abstract] insomnia is a common clinical symptom of modern social strong pressure, part of the majority has affected the health and normal life of mankind. Insomnia must due to treatment; comprehensive therapy; drug therapy and psychological therapy and into, so as to solve insomnia problems fundamentally, thus more healthy and wonderful life. This article is about the use of sedative hypnotic drugs how reasonable and combined with other auxiliary drug use, at the same time to counseling, acupuncture point massage, treatment options and develop a reasonable to solve insomnia troubles, so that they can have a good sleep.
口吃者的自我治疗
《口吃者的自我治疗》第10修订版 作者：Malcolm Fraser,L.H.D. 美国语音语言听力协会(ASLHA)的终生会员美国口吃基金会(SFA)的创建者 中文翻译作者：童 镭 （Ray Tong）翻译始于：2004-10-31 美国口吃基金会（SFA） 网址：https://www.sodocs.net/doc/5c2954710.html, 本书的发行历史： 1. 1978年首次出版 2. 2000年第九版 3. 2002年第十版 4. 2004年第十修订版 出版单位：美国口吃基金会（Stuttering Foundation of America）3100 Walnut Grove Road, Suite 603P.O. Box 11749Memphis, Tennessee 38111-0749 图书馆目录索引号：No.00-133443出版文号：No.0012 ISBN 0-933388-45-4美国口吃基金会保留版权1978，1993，2000，2002，2004 美国口吃基金会（SFA）是一个致力于口吃预防和治疗的非盈利性组织。为该组织所提供的捐款是免税的。 在美利坚合众国印刷。 献给所有正在口吃苦海中苦苦挣扎的人们！ 亲爱的读者： 无论何时何地，总会有一些口吃患者不能得到专家们的专业帮助，而另外的一些口吃患者就算能够得到这些专业的帮助，却好像丝毫也不能从中获得理想的治疗效果。总会有一些口吃患者，他们更愿意成为自己的口吃矫正师，“依靠自己来解决自己的问题”。 在本书当中，Malcolm Fraser,美国口吃基金会的创建者，为那些必须依靠自身力量来帮助自己的人，提供了一些指导。由于其自身曾是一名严重的口吃患者，他深深地了解作为一名口吃患者在进行自我治疗时所面对的困难。针对这些困难，他为我们列出了一系列的“目标”和“自我挑战”。 这些“目标”和“自我挑战”就像是一份地图！一份所有深陷于阴冷凄凉的口吃沼泽中的人们都需要的地图，一份所有想要从这个沼泽中找到一条“解脱之道”的人们都渴望的“地图”！ —— 查尔斯·范·瑞普（Charles Van Riper）原美国西密歇根州立大学，语言病理与听力学学院，院长著名的荣誉退休教授 “口吃患者必须自己征服自己的问题。没有其他任何人能够代替他做这件事！” —— Van Riper 《口吃者的自我治疗》第10修订版·目录 所有与口吃相关的特殊词语和表达。如果您想了解它们的更详细的信息和书中的出处的话，请使用189页的索引！ 1. 关于自我治疗 2. 关于本书中所提供的自我治疗方法 1. 导致口吃的根本原因
Excel中函数的使用方法
各函数使用方法大全 Excel函数使用方法 1、ABS函数 主要功能：求出相应数字的绝对值。 使用格式：ABS(number) 参数说明：number代表需要求绝对值的数值或引用的单元格。 应用举例：如果在B2单元格中输入公式：=ABS(A2)，则在A2单元格中无论输入正数（如100）还是负数（如-100），B2中均显示出正数（如100）。 特别提醒：如果number参数不是数值，而是一些字符（如A等），则B2中返回错误值“#VALUE！”。 2、AND函数 主要功能：返回逻辑值：如果所有参数值均为逻辑“真（TRUE）”，则返回逻辑“真（TRUE）”，反之返回逻辑“假（FALSE）”。 使用格式：AND(logical1,logical2, ...) 参数说明：Logical1,Logical2,Logical3……：表示待测试的条件值或表达式，最多这30个。 应用举例：在C5单元格输入公式：=AND(A5>=60,B5>=60)，确认。如果C5中返回TRUE，说明A5和B5中的数值均大于等于60，如果返回FALSE，说明A5和B5中的数值至少有一个小于60。 特别提醒：如果指定的逻辑条件参数中包含非逻辑值时，则函数返回错误值“#VALUE!”或“#NAME”。 3、AVERAGE函数 主要功能：求出所有参数的算术平均值。 使用格式：AVERAGE(number1,number2,……) 参数说明：number1,number2,……：需要求平均值的数值或引用单元格（区域），参数不超过30个。 应用举例：在B8单元格中输入公式：=AVERAGE(B7：D7,F7：H7,7,8)，确认后，即可求出B7至D7区域、F7至H7区域中的数值和7、8的平均值。 特别提醒：如果引用区域中包含“0”值单元格，则计算在内；如果引用区域中包含空白或字符单元格，则不计算在内。 4、COLUMN 函数 主要功能：显示所引用单元格的列标号值。 使用格式：COLUMN(reference) 参数说明：reference为引用的单元格。
人力资源常用EXCEL函数汇总
1、利用身份证号码提取员工性别信息 我国新一代的18 位身份证号码有一个很明显的特征，身份证号的倒数第2 位是奇数，为男性，否则是女性。根据这一特征，利用MID 和TRUNC两个函数判断员工的性别，而不必逐个输入，这样既避免了输入的烦琐工作，又保证了数据的正确性 操作步骤： 在单元格区域E3:E19 中输入员工的身份证号码。 MID 返回文本字符串中从指定位置开始指定数目的字符，该数目由用户指定。格式：MID(text,start_num,num_chars)。参数：text（文本）代表要提取字符的文本字符串；start_num（开始数值）代表文本中要提取字符的位置，文本中第1 个字符的start_num 为1，以此类推；num_chars（字符个数）指定MID 从文本中返回字符的个数。
函数TRUNC 的功能是将数字的小数部分截去，返回整数。格式：TRUNC(number,num_digits)。参数：number（数值）需要截尾取整的数字。num_digits（阿拉伯数字）用于指定取整精度的数字，num_digits 的默认值为0。 2、利用身份证号码提取员工出生日期信息 利用身份证号码来提取员工的出生日期，既准确又节省时间。具体操作步骤如图
函数TEXT 功能是将数值转换为指定数字格式表示的文本。格式：TEXT(value,format_text)。参数：value（数值）指数值、计算结果为数字值的公式，或对包含数字值的单元格的引用；format_text（文本格式）为【单元格格式】对话框中【数字】选项卡上【分类】文本框中的文本形式 的数字格式。函数LEN 功能是返回文本字符串中的字符数。格式：LEN(text)。参数：text 表示要查找的文本，空格将作为字符进行计数。 3、计算员工年龄 企业中的职务变动和员工的年龄有密切的关系，员工年龄随着日期变化而变动，借助于函数YEAR 和TODAY 可以轻松输入。 选择单元格区域F3:F19，单击【开始】选项卡，在【数字】组中单击
FREQUENCY函数说明
FREQUENCY函数说明 计算数值在某个区域内的出现频率，然后返回一个垂直数组。例如，使用函数FREQUENCY 可以在分数区域内计算测验分数的个数。由于函数 FREQUENCY 返回一个数组，所以它必须以数组公式的形式输入。 语法 FREQUENCY(data_array,bins_array) Data_array 是一个数组或对一组数值的引用，您要为它计算频率。如果 data_array 中不包含任何数值，函数 FREQUENCY 将返回一个零数组。 Bins_array 是一个区间数组或对区间的引用，该区间用于对 data_array 中的数值进行分组。如果 bins_array 中不包含任何数值，函数 FREQUENCY 返回的值与 data_array 中的元素个数相等。 说明：在选择了用于显示返回的分布结果的相邻单元格区域后，函数 FREQUENCY 应以数组公式的形式输入。返回的数组中的元素个数比 bins_array 中的元素个数多 1 个。多出来的元素表示最高区间之上的数值个数。例如，如果要为三个单元格中输入的三个数值区间计数，请务必在四个单元格中输入 FREQUENCY 函数获得计算结果。多出来的单元格将返回 data_array 中第三个区间值以上的数值个数。 函数 FREQUENCY 将忽略空白单元格和文本。如果公式的返回结果为数组，该公式必须以数组公式的形式输入。本示例假设所有测验分数都是整数。 请选择从公式单元格开始的区域 A13:A16。按 F2，再按 Ctrl+Shift+Enter。如果公式未以数组公式的形式输入，则返回的结果为 1。 若分段数组无序，则分段情况不变，但显示规律是：假设分段数组为a\b\c\d\e\f\g。则A位置显示<=A的部分,B位置显示<=B的部分……依此类推，F位置显示<=F的部分,G位置显示<=G的部分，最后显示>最大数的部分。
儿童口吃的预防与矫正
儿童口吃的预防与矫正 Barry Guitar 如果你的孩子说话时有困难，在说一些特定的音节、字词时容易停顿或重复，他就可能有口吃的问题。不过，正如大多数孩子学习语言的经历，这也可能仅仅是一个正常的说话不流畅的阶段。这本手册，将帮助你理解口吃和正常的语言发展的区别。 正常的说话不流畅儿童 1，这些正常的说话不流畅的儿童，偶尔会有一两次字词的重复，就、就、就象这样。不流畅的表现，还可能包括停顿和“哦”、“噢”、“呣”之类的口头禅。 2，这种不流畅，最可能在1岁或1岁半至5岁之间发生，而且会时有时无。 通常，这些是儿童用新的方法来学习语言的迹象。如果这种不流畅在消失几个星期后重又发生，可能说明这孩子到了语言学习的另一个阶段。 轻微口吃的儿童 1，轻微口吃的儿童，会有两次以上的重复，就、就、就、就、就象这样。面部肌肉，尤其嘴部的，会表现出明显的紧张和努力说话。 2，他的声调可能会提高，说话会有重复，偶尔可能会有阻塞——几秒钟内没有气流或声音。 3，这种说话的不流畅，可能时有时无，但出现的次数更多。 4，不费力的重复或拖延，是口吃中最无害的形式。任何方法，只要可以让你的孩子用这种形式口吃，而不是紧张的口吃，或避免某些词语，都是有利的。 如何马上帮助 *尝试用放慢的轻松的方式，跟你的孩子说话，并让家庭的其他成员也这么做。不要把话说得太慢以致听起来不正常，只需从容不迫地说话，多多停顿。电视里的赵忠详，就是这种说话方式的模范榜样。 *每天用一些时间和你的孩子在一起，给予他全部的注意，用放慢的轻松的方式说话，是最为有效的。每天用几分钟时间，不做其他事情，倾听你的孩子说话，无论什么内容。 *当你的孩子与你说话，或提出问题时，你可以尝试在回答前，停顿一秒钟左右。这可以使谈话更为从容不迫，更为轻松。 *当你的孩子，口吃加剧时，不要心烦苦恼。你的孩子正一直在尽最大的努力来学习新的说话技巧，而你的耐心和接受，会帮助他。 *如果你的孩子，在口吃加剧时，变得沮丧不安，那就好好的安慰他。有的孩子会对你说的话有良好反应，“我知道有时说话会是件难事……但很多人会说不出某个词……这没什么问题。”有的其他孩子，当他们沮丧时，会因你的触摸和拥抱得到安慰。 危险因素 1，家族的口吃历史：如果家庭成员中有人仍然口吃时 2，发生口吃的年纪：从3.5岁后发生 3，从初次发现口吃至今：6-12个月甚至更长时间 4，其他语言发展上的缓慢：如说话的错误，难以跟随他人指示语 其他的一些因素，同样可能使儿童处于口吃的危险之中。知道这些因素，会帮助你决定，是否你的孩子需要去言语病理师处接受检查。如果你的孩子有以上这些危险因素的一个或更多，你应该更为注意。对于这些危险因素的更详细的解释。
小孩子口吃怎么办
小孩子口吃如何应对 “妈……妈……，其…其实我……我很想……流…流利地说……说话。”这应该是很多口吃的小孩的内心独白吧。 其实2岁的孩子出现结巴是很正常，1岁到3岁之间，都是幼儿口语发展的快速期，从两三岁开始会说短的句子，思维想象也在快速发展。孩子对世界充满好奇，就会有很多话要说，但她的词汇量没有成人多，做不到顺畅地表达，她们说话像我们学外语时一样，脑子想得很快，嘴里说不出，就容易磕巴。 一般情况下，2岁的孩子说话结巴，它只是一种暂时的口吃现象，不需要定论为口吃。一般称为语言的过渡期，大部分孩子都会在学语言中间会碰到这种情况。一般孩子在6岁内外语言发育已经协调的情况下，是可以自行恢复的。只有少数的才会过渡成为口吃患者。 口吃的表现形式 口吃的表现形式很多样，医学上通常把它分为三大类：首字难发型、语词重复型、语句中断型。而96%的口吃表现为首字难发。多数患儿初期仅有言语症状，部分严重患者可有唇、下颌、颈部肌肉痉挛、舌肌震颤、跺脚、眨眼、转头等因生理紧张而产生的各种伴随动作。此时，父母的态度、社交受挫、精神压力等因素可促使口吃不断加重及伴随动作增多。 1、首字难发型：表现为第一字发音时发不出，第一字重复，话语中途某字发音障碍； 2、语词重复型：经常出现语音或音节的重复或延长，影响说话的流畅性； 3、无表达内容障碍；因发音-呼吸器官的紧张性痉挛，导致语言节奏失调 4、排除抽动症及其他神经系统疾病。患儿说话时，可伴有跺脚、摆手、挤眼、歪嘴、口唇颤抖、躯干摇晃等动作。部分患儿常易兴奋或激惹，并伴有情绪不稳和睡眠障碍等。 随年龄的增长，患儿还可出现焦虑不安、害羞、容易激怒，不愿参加集体活动，上课不敢发言，不喜欢交往，变得孤独退缩等情绪与行为的异常，如不予矫治最终可导致顽固性口吃。 口吃的原因 1、遗传因素：口吃患者家族发病率可达36%～55%，故有人认为与遗传因素有关，可能为单基因遗传。有人发现的孩子口吃是有家族遗传史，主要外因是
矫正口吃的有效口才训练方法
矫正口吃的有效口才训练方法 科学研究已经证明;口吃仅仅是一种通过模仿和某种暗示所形成的不良习惯，并不是发音器官有病变性毛病或遗传性疾病，更不是口吃者思维力迟钝，通过训练是完全能够矫正的。现在为你分享了矫正口吃的有效口才训练方法，希望能够帮到你。 (一)矫正式训练法1.朗读矫正法 朗读能保持语言的连贯性，可以不断提高大脑皮层和发音器官的协调能力，有助于口吃的矫正。口吃者大都有说话时即表现得心慌性急、肌肉紧张、急欲把话快速说完的心理内驱力。为消除这一毛病，可以拿一篇自己熟悉的课文或文章来朗读。读前，把心情平静下来并使肌肉放松。开始朗读时，先慢速度进行并注意轻读每一句话的第一字音和句中词组的首字音。如这样一段文字：我们一定要兢兢业业地做好自己的工作，加强同全国各族人民的团结，加强同全世界人民的团结，为把中国建设成为现代化的、高度文明、高度发达的社会主义国家而努力奋斗。 2.写字矫正法 说与写有着极为密切的关系。有位科学家要求口吃者把他们所写的一切都用印刷体规矩地写出来。这潦潦草草地写要多花费2;3倍的时间。据说有的口吃患者坚持这样写字一星期，讲话的节奏逐渐均匀，最后就不再口吃了。这是因为一丝不苟地写字会养成从容不迫的思维
习惯。 3.字音纠正法 口吃的人有个毛病，即常对某些字的发音有困难。如遇到有声母b、p、m或zh、ch、sh的字音就口吃。口吃患者注意自己在哪些字上口吃，就把这些字单独记下来，进行专门训练。 4.体育疗法 经常参加体育锻炼，特别是经常做深呼吸对矫正口吃也很有帮助。这是因为口吃患者有个特点，说话时心情紧张，急于把话说完，造成气短，从而破坏语言节奏，形成紊乱现象，使口吃加重。所以口吃患者要经过体育活动，多做深呼吸，说话要慢一点，心情不必紧张，说不出来不硬说，停顿一会。这样长期坚持下去，会使大脑皮层对发音器官的协调能力得到改善，建立起新的条件反射，使口吃的不良习惯得到矫正。工夫不负有心人。经验证明：只要持之以恒地练习，一般只要半年就可以把口吃矫正过来。 (二)锻炼式训练法1. 克服口吃的最好办法就是让自己慢半拍。心里急，不要紧，关键是强制自己缓和，把话想清楚了再说，把话组织好以后再说。可以用一些过渡的语句，比如，“我是这样想的”,“我认为”,“恩。。”,“能不能这样说”,“我想说...”,或者“哈哈..”,“你说得好。。”,“你们看法不错”,“我有一个意见...”等等来缓冲自己的思维，等自己把话组织完，再脱口而出比拉锯子一样讲出来会好很多。拉锯子就是常说的口吃。 2. 口吃不是言语表达不强，任何人紧张时都会出现。目标就是
相关文档
- FREQUENCY函数应用解析
- 实验设计与数据处理 第二章 数据的表图表示方法
- 数据分组(讲解灯泡的使用寿命)
- FREQUENCY函数
- FREQUENCY函数的使用
- 计算机应用基础第4章 中文Excel 2010
- EXCEL应用与统计图表的制作ppt课件
- 查找不重复值函数方法集锦_chrisfang
- EXCEL练习题目讲解
- 数据分组(讲解灯泡的使用寿命)
- 在Excel中使用FREQUENCY函数统计各分数段人数
- FREQUENCY函数的使用
- excel FREQUENCY函数的使用
- Excel中frequency函数怎么用
- 从零开始学函数
- FREQUENCY函数说明
- 终版Excel数据分析..pptx
- Excel财务处理中用到的函数的使用方法及实例
- 电脑一级Ecel函数使用方法
- Excel中使用Fequency函数分区间统计数值个数