Natural Waking and Sleep States: A View From Inside
Neocortical Neurons
M. STERIADE, I. TIMOFEEV, AND F. GRENIER
Laboratoire de Neurophysiologie, Faculté de Médicine, Université Laval, Quebec G1K 7P4, Canada
Received 15 November 2000; accepted in final form 22 January 2001
Steriade, M., I. Timofeev, and F. Grenier. Natural waking and sleep
states: a view from inside neocortical neurons. J Neurophysiol 85:
1969 –1985, 2001. In this first intracellular study of neocortical activ-
ities during waking and sleep states, we hypothesized that synaptic
activities during natural states of vigilance have a decisive impact on
the observed electrophysiological properties of neurons that were
previously studied under anesthesia or in brain slices. We investigated
the incidence of different firing patterns in neocortical neurons of
awake cats, the relation between membrane potential fluctuations and
firing rates, and the input resistance during all states of vigilance. In
awake animals, the neurons displaying fast-spiking firing patterns
were more numerous, whereas the incidence of neurons with intrin-
sically bursting patterns was much lower than in our previous exper-
iments conducted on the intact-cortex or isolated cortical slabs of
anesthetized cats. Although cortical neurons displayed prolonged hy-
perpolarizing phases during slow-wave sleep, the firing rates during
the depolarizing phases of the slow sleep oscillation was as high
during these epochs as during waking and rapid-eye-movement sleep.
Maximum firing rates, exceeding those of regular-spiking neurons,
were reached by conventional fast-spiking neurons during both wak-
ing and sleep states, and by fast-rhythmic-bursting neurons during
waking. The input resistance was more stable and it increased during
quiet wakefulness, compared with sleep states. As waking is associ-
ated with high synaptic activity, we explain this result by a higher
release of activating neuromodulators, which produce an increase in
the input resistance of cortical neurons. In view of the high firing rates
in the functionally disconnected state of slow-wave sleep, we suggest
that neocortical neurons are engaged in processing internally gener-
ated signals.
INTRODUCTION
Previous studies conducted in brain slices and in animals
under deep anesthesia have described the electrophysiological
properties of neocortical neurons (Connors and Gutnick 1990;
McCormick et al. 1985; Nuñez et al. 1993), their multiple ionic
conductances (Crill 1996; Schwindt et al. 1988a,b, 1989), and
their propensity to generate and synchronize a slow oscillation
at 0.5–1 Hz (Steriade et al. 1993d,e). It was also shown that
some firing patterns may be altered by setting into action
generalized modulatory systems in anesthetized animals (Ste-
riade et al. 1993a) or applying activating neurotransmitters in
cortical slices (Wang and McCormick 1993). Similarly, firing
patterns elicited by intracellular depolarizing current pulses
could be transformed into different ones by synaptic activity in
acutely prepared animals (Steriade et al. 1998a).
Address reprint requests to M. Steriade (E-mail: mircea.steriade@phs.
ulaval.ca).
www.jn.physiology.org 0022-3077/01 $5.00 Copyright © 2001 The American Physiological Society
Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.
In view of these results, we started the present intracellular
study in chronically implanted, naturally sleeping, and aroused
animals with the hypothesis that synaptic activities during
natural states of vigilance may have a decisive impact on the
electrophysiological properties of neurons. We wanted to com-
pare the firing patterns of various neuronal types and their
incidence during natural wakefulness to those previously de-
scribed in acute experiments. We also assumed that the con-
dition of a chronically implanted animal would allow us to
compare the intracellular characteristics of the slow oscillation
during natural sleep to those previously recorded only under
anesthesia (Contreras and Steriade 1995; Contreras et al. 1996;
Steriade et al. 1993d,e). Finally, we hypothesized that, despite
the increased synaptic activity during the alert state, the actions
of some neuromodulators released by generalized activating
systems may change the expected result of an increased mem-
brane conductance.
The state of sleep with slow waves of brain electrical activity
(SWS) was once thought to be associated with a global cortical
inhibition that radiates to subcortical structures (Pavlov 1923).
This would relegate the brain to complete inactivity and loss of
mental processes during this sleep stage. With the advent of
extracellular unit recordings in behaving animals (Jasper et al.
1960), it was shown that long-axoned neurons in the motor
cortex of monkeys, which were antidromically activated from
the thalamus, brain stem, and spinal cord, did not cease firing
during SWS; however, their discharge patterns were different
from those displayed by the same neurons in the two states of
vigilance associated with an alert brain, waking and rapid-eye-
movement (REM) sleep (Evarts 1964; Steriade et al. 1974).
The rates and patterns of extracellularly recorded neocortical
neurons have also been investigated in visual and association
areas of chronically implanted cats (Hobson and McCarley
1971; Noda and Adey 1970; Steriade 1978). Until now, the
mechanisms underlying the prolonged periods of neuronal
silence during natural SWS have not been elucidated. To
uncover the neuronal mechanisms underlying the physiological
correlates of waking and sleep states requires intracellular
recordings from identified neurons. In previous studies on
waking and sleep states, spinal and brain stem motoneurons
(Chase and Morales 1983; Chase et al. 1980; Glenn and De-
ment 1981), brain stem reticular neurons (Ito and McCarley
1984), and thalamic relay neurons (Hirsch et al. 1983) have
The costs of publication of this article were defrayed in part by the payment
of page charges. The article must therefore be hereby marked ‘‘advertisement’’
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1969
1970 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

been recorded intracellularly. Although intracellular recordings
have also been used in neocortex for conditioning studies
(Woody et al. 1978) and investigations on fast oscillations
(Murthy and Fetz 1992) in alert animals, this method has not
yet been used in the neocortex throughout the long periods of
the natural waking-sleep cycle.
In the present study, we were interested in 1) the firing patterns
of different cell types and their incidence in alert animals, as
compared with our previous studies on similar cell types recorded
under anesthesia; 2) the relation between fluctuations in mem-
brane potential (Vm) and firing rates during wakefulness and sleep
states; and 3) the state-dependent variations in the input resistance
(Rin), a measure resulting from passive electrical neuronal prop-
erties and balanced changes in excitatory and inhibitory inputs
from afferent (specific and generalized modulatory) pathways.
Preliminary data have been published in abstract form (Steriade et
al. 1999, 2000).
METHODS
Preparation, recording, and stimulation
Experiments were conducted on four adult cats. Surgical proce-
dures for chronic implantation of recording and stimulating electrodes
were carried out under deep barbiturate anesthesia (Somnotol, 35
mg/kg, ip), followed by two or three administrations, every 12 h, of
buprenorphine (0.03 mg/kg, im) to prevent pain. Penicillin (500,000
units im) was also injected during 3 consecutive days.
The cats were implanted with one to three chambers allowing the
intracellular penetrations of micropipettes [filled with 2.5–3 M potas-
sium acetate (KAc) or 1.5–3 M potassium chloride (KCl), dc resis-
tances 25 to 50 M⍀], field potentials recordings using coaxial mac-
roelectrodes (with the tip in the cortical depth at about 0.8 –1 mm and
the ring placed at the cortical surface), and insertion of coaxial
stimulating electrodes into different cortical areas and related thalamic
nuclei for the antidromic and orthodromic identification of the input-
output organization of recorded neurons. The antidromic identification
of a callosal neuron, activated by stimulating the homotopic point in
the contralateral cortical area, is shown in Fig. 12. The state-depen-
dent changes in cellular responsiveness to antidromic and orthodromic
volleys will be reported elsewhere. In different animals, the chambers
were inserted over the pericruciate (motor) and anterior suprasylvian
(association) gyri, or coronal (primary somatosensory) and posterior
suprasylvian (visual association) areas. In addition, we recorded the
electroencephalogram (EEG) from the vicinity of intracellular record-
ings as well as from distant cortical areas (to determine whether or not
long-range synchronization between neuronal activity and EEG is
present in natural SWS), the electro-oculogram (EOG) from pairs of
electrodes placed in ocular cavities, and the electromyogram (EMG)
from neck muscles.
The method used to keep the head rigid without pain or pressure
during the recording sessions was similar to that described previously
(Steriade and Glenn 1982). After surgery and 4 –5 days of training to
sleep in the stereotaxic apparatus, cats started to display normal
sleep-waking cycles and, at that time, intracellular recordings began
after small perforations in the dura were carefully made. The chamber
was filled with warm sterile solution of 4% agar. As a rule, two to
three recording sessions, each lasting for 1–3 h, were performed daily,
and 7–10 days of recordings could be made in each chamber. The cats
were not deprived of sleep between recording sessions. During re-
cordings, the animals could move their limbs and they often made
postural adjustments (see Fig. 1). The criteria for differentiating the
three major states of vigilance (waking, SWS, and REM sleep) by
EEG, EOG, and EMG are found elsewhere (Steriade and McCarley
1990; see also Figs. 4 –5). The experimental protocol was approved by

FIG. 1. Intracellular recording of cortical neuron during active waking. Neuron from suprasylvian association area 7 was
recorded together with electroencephalogram (EEG) from posterior suprasylvian area 21, electro-oculogram (EOG) and electro-
myogram (EMG). Note stability of intracellular recording despite numerous eye movements and phasic increases in muscular tone.
Period indicated by horizontal bar is expanded at right (arrow). In this and following figures, Vm is indicated (⫺66 mV).

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE 1971

FIG. 2. Electrophysiological identification of different cell classes. Left: responses of regular-spiking (RS), fast-rhythmic-
bursting (FRB), fast-spiking (FS), and intrinsically-bursting (IB) neurons from area 4 to depolarizing current pulses (0.2 s, 0.8 nA).
At right of each depolarizing current pulse, action potentials of each cell classes; note thin spikes of FRB and FS neurons, compared
with those of RS and IB neurons. Right: width of action potentials (at half-amplitude) in a sample of 117 neurons (48 RS, 37 FRB,
24 FS, and 8 IB, corresponding to patterns depicted at left). See details in text.

the committee for animal care in our university and also conforms to
the policy of the American Physiological Society.
At the end of the experiments, the cats were given a lethal dose of
pentobarbital.
RESULTS
Database and proportions of different cell classes
Stable recordings, lasting for at least 15 min, but up to 90
min, were obtained from 750 neurons recorded from primary
somatosensory, motor, and association (visual and somatosen-
sory) cortical areas. The stability of intracellular recordings
was achieved even during periods of active waking, associated
with numerous eye movements and phasic increases in mus-
cular tone due to postural adjustments (Fig. 1). The intracel-
lular activity could be investigated during the whole sleep-
waking cycle in 34 neurons, while 320 neurons were studied in
two behavioral states of vigilance with opposite features: SWS
and REM sleep or SWS and waking.

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

1972 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE 1973

To determine the proportions of different discharge patterns
of various neuronal classes in alert animals, we used a sample
of 120 neurons that were selected because depolarizing current
pulses could be applied during the steady state of quiet waking,
without phasic motor events. In keeping with the results from
previous in vitro studies (Connors and Gutnick 1990; Kawagu-
chi and Kubota 1997; McCormick et al. 1985; Thomson and
Deuchars 1997) and in vivo experiments on acutely prepared
animals (Gray and McCormick 1996; Nuñez et al. 1993; Ste-
riade et al. 1998a), neurons were classified into four categories
according to their responses elicited by intracellular depolar-
izing current pulses: regular-spiking (RS), intrinsically burst-
ing (IB), fast-spiking (FS), and fast-rhythmic-bursting (FRB)
(Fig. 2). The firing pattern was very similar to that previously
described in vitro and in vivo under anesthesia. RS and IB
firing patterns are typical of pyramidal cells recorded in pre-
vious studies and are therefore here taken to be indicative of
excitatory cortical neurons. Conventional FS patterns are usu-
ally observed in inhibitory interneurons and cells with this
behavior are generally assumed to be inhibitory. It was, how-
ever, reported that while some interneurons discharge like
conventional FS cells, other local inhibitory interneurons fire
like RS or bursting cells (Thomson et al. 1996). On the other
hand, FRB neurons display fast (300 – 600 Hz), rhythmic
(20 –50 Hz) spike-bursts at given levels of depolarization, but
below that level they exhibit RS patterns and above it they
discharge like FS neurons (Steriade et al. 1998a). While some
FRB neurons are pyramids located in layers II/III (Gray and
McCormick 1996), other FRB neurons are deeply lying corti-
cothalamic cells, as shown by their antidromic activation from
the thalamus, and still other FRB neurons were intracellularly
stained and found to be local-circuit, sparsely spiny, or aspiny
neurons (Steriade et al. 1998a).
Out of 120 neurons tested with depolarizing current pulses
during the steady waking state, we found RS patterns in 61
neurons (51%), FRB patterns in 25 neurons (21%), FS patterns
in 29 neurons (24%), and IB patterns in 5 neurons (4%). Thus
although the firing pattern of various cell classes was very
similar to that previously described in slices maintained in vitro
and in acutely prepared (anesthetized) animals, the proportions
of FS and IB firing patterns were different from those previ-
ously found in anesthetized animals with intact cortex or small
isolated slabs (Timofeev et al. 2000) and in cortical slices
maintained in vitro (see DISCUSSION).
We determined the duration of action potentials at half-
amplitude in samples from all cortical cell types, namely 48 RS
neurons, 37 FRB neurons, 24 FS neurons, and 8 IB neurons,
tested in different (waking and sleep) states. Note more nu-
merous neurons with IB patterns when also recorded during the
sleep state (n ⫽ 8), compared with the number found during
waking (n ⫽ 4; see also Fig. 3). Figure 2 shows the patterns of
discharge elicited by depolarizing current pulses in each of
these neuronal classes and the duration of their action poten-
tials at half-amplitude. RS neurons showed a major mode
between 0.6 and 0.75 ms, with a minor mode at 0.85– 0.95 ms.
By contrast, both FRB and FS neurons demonstrated much
shorter action potentials, with a mode at ⬃0.3 ms. The very
short action potentials of FRB neurons, similar to those of
conventional FS (presumably GABAergic) neurons, were also
observed in previous experiments on acutely prepared animals
in which antidromically identified corticothalamic FRB cells
(therefore glutamatergic and excitatory) displayed very short
action potentials, like inhibitory FS neurons (Steriade et al.
1998a). The small proportion of neurons that displayed IB
firing patterns during the alert state (4%) precludes accurate
assessment of spike duration in this group.
With the exception of one IB cell, in which firing patterns
were similar during all states of vigilance, in other IB neurons
(n ⫽ 4), which were analyzed during two states of vigilance
with opposing characteristics (SWS and waking, or SWS and
REM sleep), the bursting features on depolarizing current
pulses or occurring spontaneously during SWS changed into an
RS firing pattern during either waking or REM sleep. An
example of such changes is illustrated in Fig. 3 showing 1)
bursting patterns to depolarizing current pulses during SWS
and single spiking in REM sleep, and 2) similar differences in
the spontaneous firing of this neuron during these two states,
with a mode of interspike intervals at 3–3.5 ms in SWS
(lacking in REM sleep) and many more longer intervals (20 –
100 ms) during REM sleep (reflecting the single spike firing in
the latter state).
Relations between membrane potential and firing rates
in different cell types
The changes in Vm and firing patterns of an RS neuron and
an FS neuron throughout the sleep-wake cycle are illustrated in
Fig. 4. In the case of the RS neuron (Fig. 4A), SWS lasted for
almost 20 min. During this state, neuronal activity was char-
acterized by prolonged, cyclic hyperpolarizations that were
associated with depth-positive field EEG potentials, whereas
the neuron discharged tonically in both waking and REM sleep
(see the expanded periods, from the three behavioral states of
vigilance, below the upper panel). The FS neuron, recorded
with a KCl-filled pipette (Fig. 4B), exhibited similar properties,
namely tonic discharges during wakefulness, cyclic and pro-
longed hyperpolarizations during SWS, and again tonic but
irregular firing during REM sleep.
The pooled firing rates in spontaneously discharging neu-
rons, belonging to all four neuronal types, were 15.7 ⫾ 1.9 Hz
(mean ⫾ SE) during waking, 11.4 ⫾ 1.2 Hz in SWS, and
17.9 ⫾ 3.4 Hz in REM sleep. We found no significant
statistical difference between these firing rates in the three
behavioral states (paired t-test 0.2 for SWS-REM sleep; 0.9
for SWS-waking; and 0.1 for REM-waking). However,
when we calculated the firing rates for different cell types in
a sample of 120 neurons, the state-dependent firing rates
showed great differences among various neuronal types. An
example of the relation between the membrane potential and
firing rate is depicted in Fig. 5, during transition from SWS

FIG. 3. Changes in firing patterns of an IB neuron during SWS and REM sleep. Top: EEG and EMG patterns characterizing the
two states, as well as intracellular recording of this neuron together with three depolarizing current pulses (indicated by current
monitor). Bottom: responses to depolarizing current pulses (the first response is indicated by asterisk in the top). Note spike doublets
in SWS and single spiking in REM sleep. At the bottom, examples of spontaneous firing of this neuron during SWS and REM sleep.
The interspike interval histograms in each state show a mode at 3–3.5 ms in SWS (reflecting bursting activity), absence of this mode
in REM sleep, and many more longer intervals (20 –100 ms) in REM sleep, reflecting single spike firing.

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

1974 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

FIG. 4. Changes in membrane potential and firing patterns during the wake and sleep states. A: RS neuron from posterior
association suprasylvian area 21 was intracellularly recorded (together with EMG and EEG from area 5) during transition from
wake to SWS and, further, to REM sleep (there is a nondepicted period of 18 min during SWS). Periods marked by horizontal bars
are expanded below (arrows). Note tonic firing during both waking and REM sleep, and cyclic hyperpolarizations associated with
depth-positive EEG field potentials during SWS. B: activity of FS neuron (characterized by fast and tonic firing without frequency
adaptation; see at right responses to depolarizing current pulses) during waking, SWS, and REM sleep. Recording with KCl-filled
pipette. Tonic firing during waking and REM sleep was interrupted during SWS by long periods of hyperpolarizations and spindles,
corresponding to EEG depth-positive waves and spindles. Arrow indicates eye movement associated with increased firing of FS
neuron.

to REM sleep, for an RS neuron with a high discharge
frequency during SWS.
The pooled analysis of relations between the mean mem-
brane potential and mean firing rates showed that, at membrane
potentials between ⫺55 and ⫺65 mV, during the states of
waking and SWS, FS neurons discharged at much higher rates
than RS neurons (Fig. 6, top). The firing rates of RS, FRB, and
FS during all three major states of vigilance (waking, SWS,
and REM sleep) are shown at the bottom of Fig. 6. These data
also show that neurons with conventional FS firing patterns had
a propensity for higher rates, compared with RS and FRB
neurons, during all states of vigilance. Thus during the state of
waking, neurons with FS and RS discharge patterns fired at
23.7 ⫾ 6.1 and 9.4 ⫾ 1.7 Hz, respectively; at 14.9 ⫾ 4.1 and

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE 1975

FIG. 5. Relation between membrane potential and firing rate in an RS neuron from area 7, during transition from SWS to REM
sleep. Top: five traces represent depth-EEG activities from left areas 4 and 21, intracellular activity of neuron from left area 7, EOG,
and EMG. Two epochs from SWS and REM sleep are expanded below (arrows). The histograms of membrane potential in SWS
and REM sleep are illustrated below. Bottom: plots showing the relation between membrane potential and firing rates; every point
represents firing rates and the membrane potential calculated for each 0.1 s of the period shown in the top panel.

11.8 ⫾ 1.6 Hz in SWS; and at 30.6 ⫾ 8.4 and 14.0 ⫾ 2.8 Hz
in REM sleep. FRB neurons discharged at 15.0 ⫾ 2.5, 7.5 ⫾
1.9, and 5.4 ⫾ 2.4 Hz in waking, SWS, and REM sleep,
respectively; thus they fired at higher rates, compared with RS
neurons, during the waking state. The increased discharge
frequencies of FRB neurons during wakefulness is at least
partially ascribable to the fact that they fired spontaneously
with high-frequency (20 –50 Hz) spike doublets and triplets
during this behavioral state, similar to their responses elicited
by depolarizing current pulses (Fig. 6). We do not provide the

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

1976 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

FIG. 6. Pooled relations between the membrane potential and firing rates in different cell types. Top: relations between
membrane potential and firing rates in a sample of 120 neurons (RS, FRB, and FS), during waking (black symbols) and SWS (white
symbols). Bottom: mean firing rates of RS (n ⫽ 47), FRB (n ⫽ 37), and FS (n ⫽ 22) neurons during waking, SWS, and REM sleep.

mean discharge rates for IB neurons from that sample because
of their small number during wakefulness and variations
among different neurons.
SWS-related cyclic hyperpolarizations are obliterated
in waking and REM sleep
Recordings of all electrophysiologically identified cortical
cell types across the whole sleep-waking cycle demonstrated
that the SWS state was distinguished from both waking and
REM sleep by the presence of cyclic, long-lasting (0.3– 0.5 s),
high-amplitude (8 –20 mV) hyperpolarizations during which
neurons stopped firing. The mean SD of membrane potential
during SWS was higher than in wakefulness (Fig. 7). However,
the lowest values of SD were reached during SWS-related
hyperpolarizing potentials. The increase in SD during SWS
was associated with an increase in baseline fluctuations of
membrane potential, thus suggesting the presence of high
synaptic activity during brief periods of SWS.
The presence of prolonged hyperpolarizations in SWS was
seen in all recorded neurons (Figs. 4 –5 and 8 –9), that is, not
only RS neurons but also conventional FS (presumably GABA-
ergic) neurons (Fig. 4B). The fact that none of the FS inhibitory
neurons discharged during SWS hyperpolarizations suggests that
these prolonged events are not mediated by GABAergic inhibi-
tion. This idea is consistent with the persistence of SWS hyper-
polarizations in recordings with KCl-filled pipettes (see Fig. 4B)
and the measures of input resistance during different epochs of
natural sleep and waking (see Fig. 11).
The transition from SWS to either REM sleep, indicated by
muscular atonia and EEG activation (Fig. 8), or wakefulness,
indicated by EEG activation and increased muscular tone (Fig.
9), was invariably associated with the abolition of long-lasting
hyperpolarizing potentials. This change was reflected in the
disappearance of the hyperpolarizing tail (up to ⫺80 or ⫺85
mV) in the bimodal histogram of the Vm during SWS and the
appearance of a Gaussian-type histogram (Figs. 8 –9). Overall,
the mean membrane potential was ⫺62.1 ⫾ 0.5 mV during the
depolarizing component of the slow oscillation in SWS,
⫺71.7 ⫾ 0.7 mV during the hyperpolarizing component of the
slow oscillation in SWS, ⫺60.8 ⫾ 0.7 mV in REM sleep, and
⫺62.5 ⫾ 0.6 mV in wakefulness.

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE
The obliteration of prolonged hyperpolarizing epochs with
transition from SWS to brain-activated behavioral states was
accompanied by more regular discharges rates, without brisk
firing interrupted by silent periods, as shown by the sequential
histogram of discharge frequencies (see Fig. 9, in which many
0.1-s bins display higher firing rates in SWS, compared with
waking). The transition from SWS to waking initially occurred
without visible changes in the membrane potential, which
could depolarize by a few millivolts only a few seconds later
(Fig. 9).
We investigated the evolution of a change in membrane
potential with respect to the time 0 defining the onset of
brain-activated states during transitions from SWS to either
waking or REM sleep. Figure 10 illustrates the time 0 of EEG
activation with a transition from SWS to REM sleep (top) and
the evolution of Vm (0.5-s bins in left plots, 5-s bins in right
plots) in eight neurons, four of them analyzed during transition
from SWS to REM sleep, and the other four during transition
from SWS to wakefulness. The neurons showed a much higher
dispersion of the membrane potential during SWS, compared
with either REM sleep or waking, because of the succession of
hyperpolarizing and depolarizing phases of the slow sleep
oscillation. Obliteration of hyperpolarizing phases occurred at
the very onset of brain-activated states (time 0) but in at least
half of these cases (neurons a and b in transition to REM sleep,
and neurons b and d in transition to waking), the overt depo-
Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.
1977
FIG. 7. Membrane potential fluctuations
are higher during SWS than in wakefulness.
Intracellular recording of RS neuron from
left area 21 together with depth-EEG from
left areas 4 and 21, EOG, and EMG. Tran-
sition from waking to SWS. Two epochs,
one in waking and the other in SWS, are
marked by horizontal traces (below EOG)
and expanded below (arrows). The SD of the
membrane potential was calculated for every
20 consecutive milliseconds and is shown
below for waking (left) and SWS (right).
Sampling rate 125 ␮s. An increase in SD
associated with action potentials was omit-
ted. Note an increase in SD during SWS
compared with waking.
larization followed time 0 by about 5–10 s (see also the neuron
illustrated in Fig. 9).
Conversely, the first cellular sign in the transition from
waking to SWS was the appearance of prolonged hyperpolar-
izations in all types of neocortical neurons. This was associated
with depth-positive focal EEG waves, characteristic of the
slow sleep oscillation, while the successive depolarizing phase
was associated with a depth-negativity in EEG activity, on which
thalamically generated spindles were superimposed. Similar to
anesthetized preparations (Contreras and Steriade 1995; Steriade
et al. 1993e; Timofeev and Steriade 1996), the synchronous dis-
charges of neocortical neurons during the depolarizing phase of
the slow oscillation are effective in triggering thalamic neurons to
produce spindle waves (see Fig. 4B).
The input resistance of neocortical neurons is stable and
higher during quiet waking than in other, phasically or
tonically, depolarized states
Although SWS was typically characterized by cyclic and
prolonged hyperpolarizations accompanied by arrest in firing,
the pooled discharge rates of RS neurons show only slight
differences between waking and SWS (see Fig. 6). This was
due to the fact that, during the depolarizing phase of the SWS
slow oscillation, neocortical neurons discharged at rates
1978 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

FIG. 8. Cyclic hyperpolarizations characterize neocortical neurons during SWS (S) and they are blocked during REM sleep.
Intracellular recording of area 5 RS neuron, together with EEG from areas 3 and 7, and EMG. Periods marked by horizontal bars
and arrows are expanded below. The bottom plots show the membrane potential during SWS (with a tail extending up to ⫺85 mV)
and a Gaussian-type histogram during REM sleep, around ⫺60 mV. Note also slight depolarization on entering REM sleep,
associated with EEG activation and muscular atonia.

equal to or even exceeding those found in the two brain-
active states, waking and REM sleep (see Figs. 4B and 8 –9).
We tested the apparent input resistance (Rin) of cortical
neurons during all states of vigilance for two reasons. First, we
wanted to compare the membrane conductance during the
cyclic depolarizing components of the slow oscillation in SWS
with that during the tonic depolarization in waking and REM
sleep. Although the latter brain-active states are associated
with an increased activity in afferent (thalamic and some
generalized) systems and, thus, it would be expected that the
Rin in cortical neurons is lower than during the disconnected
state of SWS, the release of some activating neuromodulators
during wakefulness may change the situation (see DISCUSSION).
Second, whereas the anesthetic state is relatively uniform,
natural states of vigilance are much more diverse, with quali-
tatively different epochs even within the same state of vigi-
lance. This is the case of the hyperpolarizing and depolarizing
phases of the slow oscillation in SWS, or of the epochs without
or with ocular saccades in REM sleep.
We measured the Rin by applying intracellularly short (100

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE 1979

FIG. 9. Transition from SWS to wakefulness is accompanied by obliteration of prolonged hyperpolarizations. The firing rate
during the depolarizing phases of the slow sleep oscillation is as high as during waking. Five traces depict (top to bottom):
depth-EEG from right area 7 and left areas 3 and 7; intracellular activity of RS neuron from left area 21; and EMG. Below:
sequential histogram of firing rate (ordinate in Hz) during the whole period depicted in the top (0.1-s bins) reveals brief periods
of high-frequency firing during SWS, interspersed with silent periods corresponding to the hyperpolarizing phases of the slow
oscillation. Two epochs marked by horizontal bars (A and B) are expanded below (without EMG). Note phasic hyperpolarizations
in area 21 neuron, related to depth-positive EEG field potentials, during SWS, tonic firing on awakening marked by EEG activation
and increased muscular tone, and slight depolarization occurring only a few seconds after awakening and blockage of hyperpo-
larizations.

ms) hyperpolarizing current pulses throughout the sleep-wak-
ing cycle, in 24 neurons. This provided consistent results,
which are exemplified for one RS neuron in Fig. 11. 1) In the
whole cellular sample, the Rin was almost double during the
hyperpolarizing phase of the slow oscillation in non-REM
(SWS) sleep (30.8 ⫾ 4.3 M⍀) compared with the depolarizing
phase of this oscillation that corresponds to the EEG depth-
negativity (16.8 ⫾ 2.3 M⍀). This further suggests that the
prolonged hyperpolarization is not mediated by GABAergic
events as the latter are associated with increased membrane
conductance. 2) Rin was higher (26.4 ⫾ 2.1 M⍀) during
tonically activated epochs, without ocular saccades, in REM
sleep, compared with periods with ocular saccades (15.8 ⫾ 2.4
M⍀). This indicates that an increased membrane conductance
occurs during saccades and, indeed, as we reported elsewhere
(Timofeev et al. 2001), FS interneurons impose GABAergic
inhibitory potentials onto pyramidal neurons during ocular
saccades. 3) In contrast to the two sleep states, the Rin was

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

1980 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

FIG. 10. Sequential alterations in the Vm during transition from SWS to REM sleep and wakefulness. Top: transition from SWS
to REM sleep to indicate the time 0 taken for brain activation (arrow), as indicated by EEG changes. Three traces represent
depth-EEG from area 21, intracellular recording of area 7 RS neuron, and EMG. The panel below shows the evolution of Vm in
4 neurons (a to d) during transition from SWS to REM sleep. In all cases, each point in the left plots represents the peak in a
histogram of membrane potential distribution for 0.5-s bins, while right plots show the same epoch in 5-s bins (median and SE).
Ordinate represents mV and abscissa represents time (in s) before and after time 0. The same is shown below for the 4 neurons
during transition from SWS to waking.

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE 1981

FIG. 11. Apparent input resistance of neocortical neurons during natural states of vigilance. Top: three periods of intracellular
recording from the same RS neuron during SWS, REM sleep, and waking. Rin was measured by applying 0.1-s hyperpolarizing
current pulses, every 0.5 s. Bottom: averages of responses of this neuron during different epochs in the three states of vigilance (note
differences between the hyperpolarizing and depolarizing phases of the slow oscillation in SWS and between epochs with and
without ocular saccades in REM). The plot at bottom shows the dynamic changes of Rin during the three states of vigilance, obtained
from continuous recording throughout the sleep-waking cycle. Dots represent individual measurements of Rin; thick line and SD
bars are the means of Rin from every 10 consecutive measurements; thin line is the coefficient of variation from corresponding
periods; circles indicate ocular saccades in REM sleep. Note that, during quiet wakefulness, Rin increased and this increase was
associated with a decrease in the coefficient of variation.

remarkably stable during the steady state of waking and it We also compared, in the same neuron and during all three
reached higher values (31.3 ⫾ 2.4 M⍀) than in REM sleep or states of vigilance, the neuronal excitability estimated by the
the depolarizing phase in SWS. number of action potentials elicited by depolarizing current

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

1982 M. STERIADE, I. TIMOFEEV, AND F. GRENIER

FIG. 12. Excitability, apparent input resistance, and firing suppression elicited by contralateral cortical stimulation during sleep
and waking states. Intracellular recording of RS neuron from area 18. Three types of stimuli were used: depolarizing current pulses
(0.1 s), hyperpolarizing current pulses (0.1 s), and stimulation of the homotopic area 18 of the contralateral hemisphere. Cortical
stimuli were applied every 3 s, while depolarizing or hyperpolarizing pulses were delivered once every 6 s. Top: depolarizing
current pulses followed by cortical stimuli (see artifact), while bottom illustrates hyperpolarizing current pulses followed by cortical
stimuli. The graphs depict analyses taken from a stimulation period of 100 s (see abscissa). They show (from top to bottom) the
number of spikes elicited by depolarizing current pulses, the Rin measured by the hyperpolarizing current pulses, and the time (in
ms) of firing suppression following stimulation of the callosal pathway. During wakefulness, the neuron was activated antidromi-
cally from the contralateral cortex (see bottom right).

pulses, the Rin measured by short hyperpolarizing current
pulses, and the area of hyperpolarization associated with a
period of spike suppression produced by a synaptic volley. As
shown in Fig. 12, the number of spikes elicited by depolarizing
current pulses did not change significantly as a function of the
state of vigilance, but the Rin was much higher during wake-
fulness than during the depolarizing phase of the slow oscilla-
tion in slow-wave sleep. The area of hyperpolarization that
followed a stimulus applied to the homotopic point in the
contralateral cortical area was more stable during waking than
during both sleep stages.
DISCUSSION
We found that 1) the proportions of FS and IB firing pat-
terns, identified during natural wakefulness, are different from
those previously found under anesthesia and in cortical slices
or isolated cortical slabs in vivo; 2) compared with RS neurons,
higher firing rates were reached by FS neurons during all
natural waking and sleep states, and by FRB neurons during
wakefulness; 3) despite the prolonged hyperpolarizations dis-
played by all neuronal types during SWS, their discharge
frequencies during the depolarizing phase of the slow sleep
oscillation were as high as, or even exceeded, those during the
brain-active states of waking and REM sleep; and 4) the
apparent Rin was increased and more stable during quiet wak-
ing than during both sleep stages.
Firing patterns and discharge rates in different cell-types
during behavioral states
We compared the proportions of different firing patterns
recorded during waking in the present experiments to those
found in our previous experiments on anesthetized cats, i.e.,

Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.

 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE
more than 1,000 intracellularly recorded neurons recorded
from intact cortex (Contreras and Steriade 1995; Nuñez et al.
1993; Steriade et al. 1993a,d, 1998a) and 160 intracellularly
recorded neurons from small isolated cortical slabs (Timofeev
et al. 2000). Neurons displaying the firing patterns of conven-
tional FS (presumably local GABAergic) neurons, defined by
thin spikes and high rates of tonic discharges without fre-
quency adaptation, were much more numerous in the present
experiments on naturally alert animals (24%) than in previous
experiments on the intact cortex of anesthetized animals (12%)
or in small isolated cortical slabs in vivo (4%). On the contrary,
neurons displaying IB firing patterns were presently found in
only 4% of neurons of awake animals, whereas they represent
15% of neurons in anesthetized animals and reach 40% of
neurons in isolated cortical slabs. The difference between the
proportions of these firing patterns in any pair of our experi-
mental conditions (namely, awake versus anesthetized animals;
awake animals versus isolated cortical slabs; and anesthetized
animals with intact cortex versus isolated cortical slabs) were
highly significant (P ⬍ 0.0001, ␹2 test).
These data showing quite different proportions of firing
patterns in various cortical cell classes in different experimen-
tal conditions indicate that the intrinsic properties underlying
firing patterns are modulated by the increased synaptic activi-
ties during the waking state. The results also suggest that one
firing type may be transformed into another during natural
shifts in the state of vigilance associated with changes in
membrane polarization. Indeed, work in vivo showed that the
same neuron may pass from the RS pattern to an FRB pattern,
eventually reaching an FS pattern, by slightly increasing the
direct depolarization (Steriade et al. 1998a). These changes in
Vm, induced by direct depolarization, are within the range of
fluctuations in Vm observed with transition from SWS to either
waking or REM sleep (present data).
It is then tempting to predict that the firing patterns of RS
neurons could develop into those of FRB neurons during
activated states. Work in vitro has indeed shown that repeated
direct depolarization of RS cortical neurons may eventually
lead to FRB firing patterns (Kang and Kayano 1994). In view
of its high-frequency spike-bursts repeated rhythmically at
30 – 40 Hz (Gray and McCormick 1996; Steriade et al. 1996a,
1998a), the FRB cell type may have a great impact on cortical
and thalamic structures in the generation of fast oscillations
which are characteristic for brain-activated states (Bouyer et al.
1981; Llinás and Ribary 1993; Murthy and Fetz 1992; Steriade
et al. 1996a,b).
The FS (presumably inhibitory) neurons have been impli-
cated in the generation of fast (20 – 40 Hz) rhythms (Buzsáki
and Chrobak 1995; Llinás et al. 1991; Lytton and Sejnowski
1991; Traub et al. 1999), which characterize the spontaneous
activity in the waking state and during high alertness. These
states of network activity, accompanied by depolarized levels
of membrane potential, may transform neurons with other
firing patterns (i.e., FRB) into FS-type neurons (Steriade et al.
1998a). This would result in an increased proportion of neu-
rons identified as FS. On the other hand, the strikingly dimin-
ished proportion of IB firing patterns in the alert condition is
likely due to the relatively depolarized membrane potential,
enhanced synaptic activity, and increased release of some
modulatory neurotransmitters, all conditions that may trans-
form IB into RS firing patterns (Steriade et al. 1993a; Wang
Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.
1983
and McCormick 1993). This suggests that a high degree of
synaptic activity in the intact brain, which is lacking in brain
slices, decisively modulates and may even overwhelm the
intrinsic neuronal properties expressed by responses to direct
depolarization.
Prolonged hyperpolarizations during SWS and
depolarization accompanied by increased firing rates with
transition from SWS to either waking or REM sleep
The long-lasting hyperpolarizations that sculpt the cellular
discharges during natural SWS were present in all types of
neocortical neurons, including those identified as conventional
FS neurons (see Fig. 4B). The arrest in firing of formally
identified, intracellularly stained, inhibitory aspiny basket cells
during the prolonged hyperpolarizations of the slow oscillation
was also reported in anesthetized animals (Contreras and Ste-
riade 1995). Together with the present demonstration that the
prolonged hyperpolarizations are not affected in recordings
with KCl-filled pipettes (Fig. 4B; see also Timofeev et al.
2001), these data indicate that these long-lasting sleep hyper-
polarizations are not mediated by GABAergic events. Instead,
they are likely due to decrease or cessation of excitatory input
(disfacilitation) and accompanied by an increase in the appar-
ent Rin (Contreras et al. 1996; Timofeev et al. 1996).
The hyperpolarizations associated with the slow oscillation
(⬍1 Hz) are the first intracellular sign with transition from
waking to sleep (Fig. 7) and they are blocked with transition
from SWS to either waking or REM sleep (Figs. 8 –9). The
increased firing rates during the transitions to both brain-active
states resulted from the blockade of SWS hyperpolarizations
and preceded in many instances the overt depolarization that
occurred only later on (Figs. 9 –10). This depolarization was
probably a consequence of increased firing rates in thalamo-
cortical neurons (Glenn and Steriade 1982) and afferents from
generalized modulatory systems, such as nucleus basalis
(Buzsáki et al. 1988) and brain stem neuronal aggregates
(reviewed in Steriade et al. 1993c). Thus, in contrast to brain
stem cholinergic neurons that display a precursor increase in
firing by about 10 –20 s before EEG activation (Steriade et al.
1990), neocortical neurons are followers of this increased
activity in generalized systems, transmitted through thalamic
synaptic relays.
Here only those cortical neurons are considered that are
depolarized on awakening and increase their firing rates, com-
pared with SWS. A smaller proportion of neocortical cells are
hyperpolarized for a certain period on arousal from sleep (to be
reported elsewhere). Indeed, earlier extracellular recordings of
monkey’s precentral neurons showed a period of ⬃10 –15 s,
corresponding to the early awakening epoch, during which
fast-conducting (⬎40 m/s) pyramidal neurons stopped firing, a
phenomenon ascribed to disfacilitation because their anti-
dromic responsiveness was increased during this period (Ste-
riade et al. 1974). Intracellular recordings in acutely prepared
midpontine pretrigeminal cats confirmed the hypothesis of
disfacilitation, in view of an increased Rin during the short
period of hyperpolarization and arrest of firing on EEG acti-
vation from sleep patterns (Ezure and Oshima 1981; Inubushi
et al. 1978).
1984 M. STERIADE, I. TIMOFEEV, AND F. GRENIER
Increased and stable membrane resistance during
quiet wakefulness
The increased Rin during the steady depolarization of the
waking state, compared with the depolarizing phase of the slow
oscillation in SWS (Figs. 11–12), may seem surprising because
of the high level of synaptic activity during waking, compared
with the blockade of incoming messages from the outside
world in SWS. The Rin measured in acutely prepared animals
in vivo is reduced up to 70% during epochs associated with
intense synaptic activity, compared with relatively quiescent
periods, and increases by ⬃30 –70% after tetrodotoxin appli-
cation in vivo, approaching the in vitro values (Paré et al.
1998). The explanation of the increase in Rin in the present
experiments on nonanesthetized, naturally alert animals is
probably the higher release of acetylcholine (ACh) in cortex
during wakefulness (Jasper and Tessier 1971) and the ACh-
induced increase in Rin of neocortical neurons (reviewed in
McCormick 1992). The increase in apparent Rin during wake-
fulness may be related to earlier extracellular recordings show-
ing an increase in antidromic and synaptic responsiveness of
neocortical neurons during this behavioral state, compared
with SWS (Steriade et al. 1974).
Implications of relatively high firing rates during the
disconnected state of SWS
Taking into consideration the unexpected high firing rates of
cortical neurons during SWS, a behavioral state when the brain
is disconnected from the outside world, a reasonable hypoth-
esis is that this sleep stage, far from being associated with a
complete annihilation of consciousness, may lead to plasticity
processes due to the bombardment of target neurons by rhyth-
mic spike-trains and spike-bursts associated with the slow
sleep oscillation. This may play an important role in the con-
solidation, during SWS, of memory traces acquired during
waking, a hypothesis advanced on the basis of intracellular
recordings of neocortical and thalamic neurons during the slow
sleep oscillation (Steriade et al. 1993b). A similar hypothesis
was proposed (Buzsáki 1989) and tested experimentally in the
hippocampal system (Qin et al. 1997; Wilson and McNaughton
1994). That short-term plasticity may occur during, and outlast,
rhythmic volleys in the reentrant pathways of the thalamocor-
ticothalamic loops was demonstrated by mimicking a landmark
oscillation of early sleep stages, using rhythmic augmenting
responses in the frequency range of sleep spindles, ⬃10 Hz
(Bazhenov et al. 1998; Castro-Alamancos and Connors 1996;
Steriade et al. 1998b). Dual intracellular recordings in anes-
thetized animals have shown that after such rhythmic thalamo-
cortical volleys, as during spindles, neocortical neurons display
self-sustained activities within the frequency range of the
evoked response, a form of “memory” in this circuit (Steriade
1999), despite the fact the thalamus remained silent, under the
hyperpolarizing pressure exerted by GABAergic thalamic re-
ticular neurons (Steriade et al. 1998b). Thus during SWS,
neocortical neurons may be engaged in information processing
of internally generated signals and may be implicated in plas-
ticity processes related to operations performed during the
waking state.
We thank P. Giguère and D. Drolet for technical assistance. I. Timofeev was
a postdoctoral fellow; he is now a Fonds de la Recherche en Santé du Québec
Scholar. F. Grenier is a Ph.D. student.
Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.
This work was supported by grants to M. Steriade and, more recently, to I.
Timofeev from the Medical Research Council of Canada. The work was also
supported by grants to M. Steriade from the Natural Sciences and Engineering
Research Council of Canada, and Human Frontier Science Program.
REFERENCES
BAZHENOV M, TIMOFEEV I, STERIADE M, AND SEJNOWSKI TJ. Computational
models of thalamocortical augmenting responses. J Neurosci 18: 6444 –
6465, 1998.
BOUYER JJ, MONTARON MF, AND ROUGEUL A. Fast frontoparietal rhythms
during combined focused attentive behaviour and immobility in cat: cortical
and thalamic localization. Electroencephalogr Clin Neurophysiol 51: 180 –
187, 1981.
BUZSÁKI G. Two-stage model of memory trace formation: a role for “noisy”
brain states. Neuroscience 31: 551–570, 1989.
BUZSÁKI G, BICKFORD RG, PONOMAREFF G, THAL LJ, MANDEL R, AND GAGE
FH. Nucleus basalis and thalamic control of neocortical activity in the freely
moving rat. J Neurosci 8: 4007– 4026, 1988.
BUZSÁKI G AND CHROBAK JJ. Temporal structure in spatially organized neu-
ronal ensembles: a role for interneuron networks. Curr Opin Neurobiol 5:
504 –510, 1995.
CASTRO-ALAMANCOS MA AND CONNORS BW. Cellular mechanisms of the
augmenting response: short-term plasticity in a thalamocortical pathway.
J Neurosci 16: 7742–7756, 1996.
CHASE MH, CHANDLER SH, AND NAKAMURA Y. Intracellular determination of
membrane potential of trigeminal motoneurons during sleep and wakeful-
ness. J Neurophysiol 44: 349 –358, 1980.
CHASE MH AND MORALES FR. Subthreshold excitatory activity and motoneu-
ron discharge during REM periods of active sleep. Science 221: 1195–1198,
1983.
CONNORS BW AND GUTNICK MJ. Intrinsic firing patterns of diverse neocortical
neurons. Trends Neurosci 13: 99 –104, 1990.
CONTRERAS D AND STERIADE M. Cellular basis of EEG slow rhythms: a study
of dynamic corticothalamic relationships. J Neurosci 15: 604 – 622, 1995.
CONTRERAS D, TIMOFEEV I, AND STERIADE M. Mechanisms of long-lasting
hyperpolarizations underlying slow sleep oscillations in cat corticothalamic
networks. J Physiol (Lond) 494: 251–264, 1996.
CRILL WE. Persistent sodium current in mammalian central neurons. Ann Rev
Physiol 58: 349 –362, 1996.
EVARTS EV. Temporal patterns of discharge of pyramidal tract neurons during
sleep and waking in the monkey. J Neurophysiol 27: 152–171, 1964.
EZURE K AND OSHIMA T. Dual activity patterns of fast pyramidal tract cells and
their family neurones during EEG arousal in the cat. Jpn J Physiol 31:
717–736, 1981.
GLENN LL AND DEMENT WC. Membrane potential, synaptic activity and
excitability of hindlimb motoneurons during wakefulness and sleep. J Neu-
rophysiol 46: 839 – 854, 1981.
GLENN LL AND STERIADE M. Discharge rate and excitability of cortically
projecting intralaminar thalamic neurons during waking and sleep states.
J Neurosci 2: 1287–1404, 1982.
GRAY CM AND MCCORMICK DA. Chattering cells: superficial pyramidal neu-
rons contributing to the generation of synchronous oscillations in the visual
cortex. Science 274: 109 –113, 1996.
HIRSCH JC, FOURMENT A, AND MARC ME. Sleep-related variations of mem-
brane potential in the lateral geniculate body relay neurons of the cat. Brain
Res 259: 308 –312, 1983.
HOBSON JA AND MCCARLEY RW. Cortical activity in sleep and waking.
Electroencephalogr Clin Neurophysiol 30: 97–112, 1971.
INUBUSHI S, KOBAYASHI T, OSHIMA T, AND TORII S. An intracellular analysis of
EEG arousal in cat motor cortex. Jpn J Physiol 28: 689 –708, 1978.
ITO K AND MCCARLEY RW. Alterations in membrane potential and excitability
of cat medial pontine reticular formation neurons during naturally occurring
sleep-wake states. Brain Res 292: 169 –175, 1984.
JASPER HH, RICCI GF, AND DOANE B. Microelectrode analysis of cortical cell
discharge during avoidance conditioning in the monkey. Electroencepha-
logr Clin Neurophysiol Suppl 13: 137–155, 1960.
JASPER HH AND TESSIER J. Acetylcholine liberation from cerebral cortex during
paradoxical (REM) sleep. Science 172: 601– 602, 1971.
KANG Y AND KAYANO F. Electrophysiological and morphological characteris-
tics of layer VI pyramidal cells in the cat motor cortex. J Neurophysiol 72:
578 –591, 1994.
KAWAGUCHI Y AND KUBOTA Y. GABAergic cell subtypes and their synaptic
connections in rat frontal cortex. Cereb Cortex 7: 476 – 486, 1997.
 CORTICAL INTRACELLULAR RECORDINGS IN STATES OF VIGILANCE
LLINÁS R, GRACE AA, AND YAROM Y. In vitro neurons in mammalian cortical
layer 4 exhibit intrinsic oscillatory activity in the 10- to 50-Hz frequency
range. Proc Natl Acad Sci USA 88: 897–901, 1991.
LLINÁS RR AND RIBARY U. Coherent 40-Hz oscillation characterizes dream
state in humans. Proc Natl Acad Sci USA 90: 2078 –2081, 1993.
LYTTON WW AND SEJNOWSKI TJ. Simulation of cortical pyramidal neurons
synchronized by inhibitory interneurons. J Neurophysiol 66: 1059 –1079,
1991.
MCCORMICK DA. Neurotransmitter actions in the thalamus and cerebral cortex
and their role in neuromodulation of thalamocortical activity. Prog Neuro-
biol 39: 337–388, 1992.
MCCORMICK DA, CONNORS BW, LIGHTHALL JW, AND PRINCE DA. Compara-
tive electrophysiology of pyramidal and sparsely spiny stellate neurons of
the neocortex. J Neurophysiol 54: 782– 806, 1985.
MURTHY VN AND FETZ EE. Coherent 25- to 35-Hz oscillations in the senso-
rimotor cortex of awake behaving monkeys. Proc Natl Acad Sci USA 89:
5670 –5674, 1992.
NODA H AND ADEY WR. Firing of neuron pairs in cat association cortex during
sleep and wakefulness. J Neurophysiol 33: 672– 684, 1970.
NUÑEZ A, AMZICA F, AND STERIADE M. Electrophysiology of cat association
cortical neurons in vivo: intrinsic properties and synaptic responses. J Neu-
rophysiol 70: 418 – 430, 1993.
PARÉ D, SHINK E, GAUDREAU H, DESTEXHE A, AND LANG EJ. Impact of
spontaneous synaptic activity on the resting properties of cat neocortical
pyramidal neurons in vivo. J Neurophysiol 79: 1450 –1460, 1998.
PAVLOV IP. “Innere Hemmung” der bedingten Reflexe und der Schlaf— ein
und derselbe Prozess. Skand Arch Physiol 44: 42–58, 1923.
QIN YL, MCNAUGHTON BL, SKAGGS WE, AND BARNES CA. Memory repro-
cessing in corticocortical and hippocampal neuronal ensembles. Philos
Trans R Soc Lond B Boi Sci 352: 1525–1533, 1997.
SANCHEZ-VIVES MV AND MCCORMICK DA. Cellular and network mechanisms
of rhythmic recurrent activity in neocortex. Nature Neurosci 3: 1027–1034,
2000.
SCHWINDT PC, SPAIN WJ, AND CRILL WE. Long-lasting reduction of excitabil-
ity by a sodium-dependent potassium current in cat neocortical neurons.
J Neurophysiol 61: 233–244, 1989.
SCHWINDT PC, SPAIN WJ, FOEHRING RC, STAFSTROM CE, CHUBB MC, AND
CRILL WE. Multiple potassium conductances and their functions in neurons
from cat sensorimotor cortex in vitro. J Neurophysiol 59: 424 – 449, 1988a.
SCHWINDT PC, SPAIN WJ, FOEHRING RC, CHUBB MC, AND CRILL WE. Slow
conductances in neurons from cat sensorimotor cortex in vitro and their role
in slow excitability changes. J Neurophysiol 59: 450 – 467, 1988b.
STERIADE M. Cortical long-axoned cells and putative interneurons during the
sleep-waking cycle. Behav Brain Sci 3: 465–514, 1978.
STERIADE M. Coherent oscillations and short-term plasticity in corticothalamic
networks. Trends Neurosci 22: 337–345, 1999.
STERIADE M, AMZICA F, AND CONTRERAS D. Synchronization of fast (30 – 40
Hz) spontaneous cortical rhythms during brain activation. J Neurosci 16:
392– 417, 1996a.
STERIADE M, AMZICA F, AND NUÑEZ A. Cholinergic and noradrenergic mod-
ulation of the slow (⬃0.3 Hz) oscillation in neocortical cells. J Neurophysiol
70: 1384 –1400, 1993a.
STERIADE M, CONTRERAS D, AMZICA F, AND TIMOFEEV I. Synchronization of
fast (30 – 40 Hz) spontaneous oscillations in intrathalamic and thalamocor-
tical networks. J Neurosci 16: 2788 –2808, 1996b.
STERIADE M, CONTRERAS D, CURRÓ DOSSI R, AND NUÑEZ A. The slow (⬍1 Hz)
oscillation in reticular thalamic and thalamocortical neurons: scenario of
sleep rhythm generation in interacting thalamic and neocortical networks.
J Neurosci 13: 3284 –3299, 1993b.
Downloaded from journals.physiology.org/journal/jn (189.133.190.189) on May 9, 2021.
1985
STERIADE M, DATTA S, PARÉ D, OAKSON G, AND CURRÓ DOSSI R. Neuronal
activities in brainstem cholinergic nuclei related to tonic activation pro-
cesses in thalamocortical systems. J Neurosci 10: 2541–2559, 1990.
STERIADE M, DESCHÊNES M, AND OAKSON G. Inhibitory processes and inter-
neuronal apparatus in motor cortex during sleep and waking. I. Background
firing and responsiveness of pyramidal tract neurons and interneurons.
J Neurophysiol 37: 1065–1092, 1974.
STERIADE M AND GLENN LL. Neocortical and caudate projections of intralami-
nar thalamic neurons and their synaptic excitation from the midbrain retic-
ular core. J Neurophysiol 48: 352–371, 1982.
STERIADE M AND MCCARLEY RW. Brainstem Control of Wakefulness and
Sleep. New York: Plenum, 1990.
STERIADE M, MCCORMICK DA, AND SEJNOWSKI TJ. Thalamocortical oscilla-
tions in the sleeping and aroused brain. Science 262: 679 – 685, 1993c.
STERIADE M, NUÑEZ A, AND AMZICA F. A novel slow (⬍1 Hz) oscillation of
neocortical neurons in vivo: depolarizing and hyperpolarizing components.
J Neurosci 13: 3252–3265, 1993d.
STERIADE M, NUÑEZ A, AND AMZICA F. Intracellular analysis of relations
between the slow (⬍1 Hz) neocortical oscillation and other sleep rhythms.
J Neurosci 13: 3266 –3283, 1993e.
STERIADE M, TIMOFEEV I, DÜRMÜLLER N, AND GRENIER F. Dynamic properties
of corticothalamic neurons and local cortical interneurons generating fast
rhythmic (30 – 40 Hz) spike bursts. J Neurophysiol 79: 483– 490, 1998a.
STERIADE M, TIMOFEEV I, AND GRENIER F. Intracellular activity of various
neocortical cell-classes during the natural wake-sleep cycle. Soc Neurosci
Abstr 25: 1661, 1999.
STERIADE M, TIMOFEEV I, AND GRENIER F. Input resistance of cortical neurons
during natural states of vigilance in behaving cats. Soc Neurosci Abstr 26:
2025, 2000.
STERIADE M, TIMOFEEV I, GRENIER F, AND DÜRMÜLLER N. Role of thalamic and
cortical neurons in augmenting responses: dual intracellular recordings in
vivo. J Neurosci 18: 6425– 6443, 1998b.
THOMSON AM AND DEUCHARS J. Synaptic interactions in neocortical local
circuits: dual intracellular recordings in vitro. Cereb Cortex 7: 510 –522,
1997.
THOMSON AM, WEST DC, HAHN J, AND DEUCHARS J. Single axon IPSPs
elicited in pyramidal cells by three classes of interneurons in slices of rat
neocortex. J Physiol (Lond) 496: 81–102, 1996.
TIMOFEEV I, CONTRERAS D, AND STERIADE M. Synaptic responsiveness of
cortical and thalamic neurons during various phases of slow oscillation in
cat. J Physiol (Lond) 494: 265–278, 1996.
TIMOFEEV I, GRENIER F, BAZHENOV M, SEJNOWSKI TJ, AND STERIADE M. Origin
of slow oscillations in deafferented cortical slabs. Cereb Cortex 10: 1185–
1199, 2000.
TIMOFEEV I, GRENIER F, AND STERIADE M. Disfacilitation and active inhibition
in the neocortex during the natural sleep-wake cycle: an intracellular study.
Proc Natl Acad Sci USA 98: 1924 –1929, 2001.
TIMOFEEV I AND STERIADE M. Low-frequency rhythms in the thalamus of
intact-cortex and decorticated cats. J Neurophysiol 76: 4152– 4168, 1996.
TRAUB RD, JEFFERYS JGR, AND WHITTINGTON MA. Fast Oscillations in Cor-
tical Circuits. Cambridge, MA: The MIT Press, 1999.
WANG Z AND MCCORMICK DA. Control of firing mode of corticotectal and
corticopontine layer V burst-generating neurons by norepinephrine, acetyl-
choline and 1S, 3R-ACPD. J Neurosci 13: 2199 –2216, 1993.
WILSON MA AND MCNAUGHTON BL. Reactivation of hippocampal ensemble
memories during sleep. Science 265: 676 – 679, 1994.
WOODY CD, SWARTZ BE, AND GRUEN E. Effects of acetylcholine and cyclic
GMP on input resistance of cortical neurons in awake cats. Brain Res 158:
373–395, 1978.