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The Journal of Neuroscience, August 15, 1998, 18(16):6444-6465
Computational Models of Thalamocortical Augmenting Responses
Maxim Bazhenov1, Igor Timofeev2, Mircea Steriade2, and Terrence J. Sejnowski1, 3 1 Howard Hughes Medical Institute, The Salk Institute, Computational Neurobiology Laboratory, La Jolla, California 92037, 2 Laboratory of Neurophysiology, School of Medicine, Laval University, Quebec, Canada G1K 7P4, and 3 Department of Biology, University of California San Diego, La Jolla, California 92093
ABSTRACT
Top
Abstract
Introduction
Repetitive stimulation of the dorsal thalamus at 7-14 Hz produces an increasing number of spikes at an increasing frequency in neocortical neurons during the first few stimuli. Possible mechanisms underlying these cortical augmenting responses were analyzed with a computer model that included populations of thalamocortical cells, thalamic reticular neurons, up to two layers of cortical pyramidal cells, and cortical inhibitory interneurons. Repetitive thalamic stimulation produced a low-threshold intrathalamic augmentation in the model based on the deinactivation of the low-threshold Ca2+ current in thalamocortical cells, which in turn induced cortical augmenting responses. In the cortical model, augmenting responses were more powerful in the "input" layer compared with those in the "output" layer. Cortical stimulation of the network model produced augmenting responses in cortical neurons in distant cortical areas through corticothalamocortical loops and low-threshold intrathalamic augmentation. Thalamic stimulation was more effective in eliciting augmenting responses than cortical stimulation. Intracortical inhibition had an important influence on the genesis of augmenting responses in cortical neurons: A shift in the balance between intracortical excitation and inhibition toward excitation transformed an augmenting responses to long-lasting paroxysmal discharge. The predictions of the model were compared with in vivo recordings from neurons in cortical area 4 and thalamic ventrolateral nucleus of anesthetized cats. The known intrinsic properties of thalamic cells and thalamocortical interconnections can account for the basic properties of cortical augmenting responses.
Key words: augmenting responses; repetitive stimulation; thalamocortical network; low-threshold current; intracortical inhibition; lateral excitation
INTRODUCTION
Repetitive 7-14 Hz stimulation of the dorsal thalamic nuclei leads to the progressive enhancement of thalamic and cortical responses (Morison and Dempsey, 1943
). Augmenting cortical responses can also be obtained in animals with thalamic lesion by stimulating white matter or callosal afferents (Morin and Steriade, 1981
Despite the converging experimental evidence for the cortical origin of augmenting responses (Morin and Steriade, 1981
In a recent computer model of the low-threshold augmenting responses in networks of RE and TC cells (Bazhenov et al., 1998
MATERIALS AND METHODS
Intrinsic currents (RE and TC cells). Each TC and RE cell was modeled by a single compartment that included voltage- and Ca2+-dependent currents described by Hodgkin-Huxley kinetics (Hodgkin and Huxley, 1952
where Cm is the membrane capacitance, gL is the leakage conductance, EL is the reversal potential, Iint is a sum of active intrinsic currents (Ijint), and Isyn is a sum of synaptic currents (Ijsyn).
(1) The set of intrinsic currents used to model a TC cell included a fast sodium current, INa (for review, see Traub and Miles, 1991
All the voltage-dependent ionic currents, Ijint(t), had the same general form:
where gj is the maximal conductance, m(t) is the activation variable, h(t) is the inactivation variable, and (V
(2) Ej) is the difference between membrane potential and reversal potential.
The model for Ih took into account both voltage and Ca2+ dependencies (Bal and McCormick, 1996
where
(3) (V) and
(V) are the voltage-dependent transition rates.
The Ca2+ dependence was based on higher-order kinetics involving a regulation factor P (Destexhe et al., 1996a
Both the open and locked states of the channels contribute to Ih:
(4)
![I<SUB><UP>h</UP></SUB>=g<SUB><UP>max</UP></SUB>([O]+k[O<SUB><UP>L</UP></SUB>])(V−E<SUB><UP>h</UP></SUB>).](/content/vol18/issue16/fulltext/6444/img005.gif)
(5) The expressions for voltage- and Ca2+-dependent transition rates for all currents are given by Bazhenov et al. (1998)
4 cm2, gT = 2.0 mS/cm2, gNa = 100 mS/cm2, gK = 10 mS/cm2 and gKL = 0.003 mS/cm2 for RE cells, and Cm = 1 µF/cm2, gL = 0.01 mS/cm2, EL =
We should note that a typical feature of bursts in RE in vivo is the accelerando-decelerando patterns of the sodium spikes (Steriade et al., 1986
Intrinsic currents (CX and IN cells). The cortical CX and IN cells were two-compartment models with channels that were also modeled by Hodgkin-Huxley kinetics (Mainen and Sejnowski, 1994
where Cm and gL are the membrane capacitance and the leakage conductance of the dendritic compartment, respectively, EL is the reversal potential, VD and VS are the membrane potentials of dendritic and axosomatic compartments, respectively, IDint and ISint are the sums of active intrinsic currents in axosomatic and dendritic compartments, respectively, Isyn is a sum of synaptic currents, and g is the conductance between axosomatic and dendritic compartments.
(6) The model included a high density of the fast Na+ channels (INa) in axosomatic compartment and a low density in the dendritic compartment. A fast potassium K+ current (IK) was present in the axosomatic compartment. A slow voltage-dependent nonactivated K+ current (IKm), slow Ca2+-dependent K+ current (IKCa), and a high-threshold Ca2+ current (IHVA) were included in dendritic compartment.
The currents were modeled by Equation 2. The expressions for the voltage- and Ca2+-dependent transition rates for all currents are given by Mainen and Sejnowski (1994)
.
The firing properties of the model in Equation 1 depend on the coupling conductance between compartments (g = 1/R) and the ratio of axosomatic area to dendritic area r (Mainen and Sejnowski, 1994
Synaptic currents. All synaptic currents were calculated according to
where gsyn is the maximal conductivity, Esyn is the reversal potential, and [O](t) is the fraction of open channels.
,](/content/vol18/issue16/fulltext/6444/img008.gif)
(7) GABAA and AMPA synaptic currents were modeled by first-order activation schemes (for review, see Destexhe et al., 1994b
The release of transmitter [T] was modeled by a square pulse [T](t) = A
(8) (t0 + tmax
GABAB receptors were modeled by a higher-order reaction scheme that took into account activation of K+ channels by G-proteins (Dutar and Nicoll, 1988
In this reaction scheme, the binding of transmitter T to the receptors R0 leads to its activated form R1. The inactive form of the G-protein, G0, which is assumed to be in excess, can transform to the active form catalyzed by R1. Finally when the active form of the G-protein binds to the closed form of the channel at four binding sites, the channel opens, O. The assumption of quasistationarity for the last reaction leads to the expression [O] = [G]4/([G]4 + K).
(9) This model of a GABAB synapse yields a strong response for a prolonged burst of spikes in the presynaptic cell. In contrast, a burst with only a few spikes evokes a weak GABAB IPSP in the postsynaptic cell.
The rate constants for all synaptic kinetic equations are given by Bazhenov et al. (1998)
We should emphasize that NMDA receptors were not included in our model, because the related experimental data were obtained under ketamine anesthesia, which blocks NMDA receptors.
Network geometry. The models discussed in the paper included two layers of thalamic cells (RE-TC) and two or three layers of cortical cells (IN-CX or IN-CX1-CX2). We simulated five network models: (1) a circuit with 1 × 4 reciprocally connected RE-TC-CX-IN cells (Fig. 1A); (2) a circuit with 1 × 2 RE-TC and 2 × 2 CX-IN cells (Fig. 1B); (3) a one-dimensional four-layer chain of 27 × 4 RE-TC-CX-IN cells (Fig. 1C); (4) a one-dimensional five-layer chain of 27 × 5 RE-TC-CX1-CX2-IN cells; and (5) a two-dimensional network of 729 × 4 RE-TC-CX-IN cells. In the latter three networks, "dense proximal connections" (Destexhe et al., 1994a
RE (GABAA), RE
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Figure 1. The structure of synaptic interconnections in the thalamocortical network. A, Minimal model of 1 × 4 RE-TC-CX-IN cells. The open circles denote the excitatory (AMPA) synapses, and the filled circles denote the inhibitory (GABAA and GABAB) synapses. B, Model of 1 × 2 RE-TC and 2 × 2 CX-IN cells with lateral intracortical connections. C, Structure of the four-layer chain of RE, TC, CX, and IN cells. Diameter of connections is nine cells for intrathalamic RE
Some of the intrinsic parameters of the neurons in the network (gKL and gh for TC cells and gKL for RE cells) were initialized with some random variability (variance
~ 20% for gKL and
Average depolarization of the neuron. To characterize the augmenting responses in the two-dimensional network of RE-TC-CX-IN cells, the average depolarization
i,j was calculated for each neuron in the network:
where Vi,j(t) is the membrane potential of the cell (i, j)
(10) 
Vi,j(t);
Computational methods. All simulations described in the paper were performed using a fourth-order Runge-Kutta [RK(4)] integration method and in some cases an embedded Runge-Kutta [RK6(5)] method (Enright et al., 1995
In vivo recordings. In vivo experiments were performed on cats anesthetized with ketamine-xylazine or with barbiturate anesthesia. Field potentials and intracellular recordings were obtained from the precruciate gyrus (area 4), the suprasylvian gyrus (areas 5, 7, and 21) as well as the ventrolateral (VL) thalamic nucleus. Simultaneous double intracellular recordings were obtained from cortical area 4 neurons and thalamic VL neurons. Augmenting responses were elicited by thalamic pulse trains at 10 Hz applied to the VL, centrolateral or lateroposterior nuclei of the thalamus. The details of experimental methods are described in a companion paper (Steriade et al., 1998
RESULTS
Thalamocortical augmenting responses in vivo
Intracellular recordings were obtained from 189 TC cells and 320 cortical cells, including 37 double intracellular impalements.
Cerebellothalamic stimulation
To investigate whether the site of stimulation affects the augmenting responses, we recorded intracellular activities in the VL nucleus of thalamus simultaneously with neurons from motor cortical area 4, while stimulating cerebellothalamic projection pathways (brachium conjunctivum) at 10 Hz. Under these conditions, no augmenting response were observed either in the cortex or in the thalamus. Examples of recordings are shown in Fig. 2 (also see Timofeev et al., 1996
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Figure 2. Stimulation of cerebellothalamic projection pathways (brachium conjunctivum) does not elicit an augmenting response. Simultaneous recording of depth EEG and a cortical cell from area 4 and a TC cell from the VL nucleus. Stimulus pulse train at 10 Hz indicated by dots. Expansion of the early parts of responses to the first 5 stimuli of VL cell (bottom left) and cortical cell (bottom right) is shown. Stimulation of brachium conjunctivum reveals a monosynaptic EPSPs in the TC cell leading to spikes. When hyperpolarization during depth positivity in the EEG prevents the TC cell from firing, the cortical cell has a smaller-amplitude EPSP. The responsiveness of thalamic and cortical cells is affected by the slow oscillation but does not increment during the train of stimuli.
Intrathalamic stimulation
Local thalamic stimulation with trains of stimuli at 10 Hz consistently produced augmenting responses in thalamic and cortical neurons. The first thalamic stimulus evoked an EPSP followed by an IPSP in thalamic cells. The second stimulus, 100 msec later, arrived during the course of GABAB IPSPs in the TC cells. Under these conditions, the EPSP invariably triggered an LTS. Progressive hyperpolarization of TC cells during the first three to five stimuli resulted in progressive growth in the size of the LTS and the number of action potentials generated by TC cells. The main feature of augmenting responses in cortex recorded intracellularly was the appearance and growth in size of secondary excitation in response to the second and subsequent stimuli. This secondary excitation was time-locked with thalamic spike bursts. Figure 3, top panel, shows the augmenting responses in simultaneously recorded cortical and TC cells. After the second stimulus, a spike burst appeared in the TC cell, and a secondary EPSP appeared in the cortical cells. The TC cell reached its maximum hyperpolarization before the third and fourth stimuli, which evoked a strong LTS with five spikes in the burst. These spike bursts in the TC cells led to strong secondary excitation in the cortical cell. The depression of the IPSP and the activation of the Ih current slightly repolarized the TC cell, and the response to fifth stimulus was a burst of only four spikes, which did not affect the shape of secondary depolarization in the cortical cell. The relationship of spike bursts in the TC cell and secondary excitation in the cortical cell is clearly seen in spike-triggered averages (Fig. 3, bottom panel).
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Figure 3. Thalamic rebound spike bursts deinactivated by hyperpolarization during augmenting responses precede the depolarizing augmented responses in cortical neuron. Ketamine-xylazine anesthesia. Dual intracellular recording from VL and area 4 neurons. VL stimulated at 10 Hz. Averages (n = 5) triggered by the first action potentials (asterisks) of the first, second, and fifth responses of VL neuron show that they precede the late, augmented depolarization (dotted line) in area 4.
Augmenting responses in the basic RE-TC-CX-IN network
The simplest thalamic network model that can generate a low-threshold augmenting response during repetitive stimulation is a reciprocal pair of RE-TC cells (Bazhenov et al., 1998
The external stimulus evoked EPSPs in RE, TC, CX, and IN cells. The response of the TC cell in turn produced secondary EPSPs in CX and IN cells with a disynaptic latency (Fig. 4). Feedback RE-evoked GABAA-GABAB IPSP partially deinactivated the low-threshold Ca2+ current in the TC cell, and the next stimulus evoked an LTS leading to the augmented burst of spikes in the TC cell, which enhanced the secondary EPSP in the CX cell. Continued stimulation augmented the TC responses and, consequently, the secondary EPSPs in CX and IN cells. Thus, a simple network of four RE-TC-CX-IN cells could reproduce the main features of the augmenting responses
a two-component response with an augmenting second component
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Figure 4. Augmenting responses in the minimal model of RE-TC-CX-IN cells during repetitive 10 Hz stimulation. Both the RE and TC cells were stimulated with 100% of maximal intensity, and the CX and IN cells were stimulated with 10% of maximal intensity. A, Monosynaptic stimulation of the CX cell elicited a nonaugmenting component in the cortical EPSPs that occurred simultaneously with EPSPs in the RE and TC cells. Augmenting spike bursts in TC cells lead to a growing secondary EPSPs in the CX cell. B, Same response shown on a shorter time scale. C, Superimposed traces of the first four EPSPs in a CX cell. Open circles indicate the time of thalamic stimulation (gAMPA = 0.1 µS from CX to IN, gAMPA = 0.1 µS from CX to TC, gAMPA = 0.2 µS from CX to RE, gGABAA = 0.03 µS from IN to CX, gAMPA = 0.035 µS from TC to CX, and gAMPA = 0.02 µS from TC to IN).
Cortical augmentation occurred in the model because of the growth of TC-evoked EPSPs in CX and IN cells. Strengthening the afferent TC
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Figure 5. Influence of afferent (TC
Additional mechanisms affecting the strength of the cortical augmenting response were uncovered in a more complex RE-TC-CX-IN network as shown in Figure 1B. Figure 5B shows the responses of CX-IN cells during trains of stimuli. The lateral CX
Augmenting responses in a chain of RE-TC-CX-IN cells in response to thalamic stimulation
A network with four one-dimensional chains of RE, TC, CX, and IN cells (Fig. 1C) was analyzed to determine the influence of geometry on the augmenting responses in the cortical CX and IN cells. Repetitive 10 Hz stimulation of RE-TC cells at 100% intensity and CX-IN cells at 10% intensity led to the augmentation of the responses in the TC, CX, and IN layers during the first three or four stimuli (Fig. 6). The number of spikes per burst and the number of cells firing action potentials increased. Nearly all of the cells fired after the second stimulus. In a larger network, the size of the active region increased gradually during a long train of stimuli, leading to more gradual growth of the secondary EPSPs in CX cells.
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Figure 6. Thalamocortical augmenting responses in a chain with 27 × 4 RE-TC-CX-IN cells in response to thalamic stimulation. A, 10 Hz train of stimuli for 1 sec. Both RE and TC cells were stimulated at 100% maximal intensity, and CX-IN cells were stimulated with 10% of maximal intensity. The intensity of stimulation was maximal at the center of the network and decayed exponentially with distance from the center. B, Expanded traces from A between t =
It is worth noting that three layers of the network (TC, CX, and IN) displayed a similar augmentation during the train of stimuli, although with quite different patterns of spiking. However, the spikes in TC cells preceded the action potentials in CX-IN cells. In contrast, RE cells displayed a powerful response to the first stimulus that decremented in response to the second stimulus. The partial inactivation of the low-threshold Ca2+ current in RE cells reduced LTSs (for details, see Bazhenov et al., 1998
Figure 7, A and B, shows expanded traces of two TC-CX pairs with different locations in the network. The first pair was located near the boundary of thalamocortical network. The intensity of stimulation was low for these cells, and the TC cells displayed almost stereotyped single spike responses for the first three stimuli in the train. However, the fourth EPSP was followed by an LTS leading to additional Na+ spike. The CX cells displayed a two-component EPSP for the first shock, in which the second component was a result of the spike bursts in the TC cells. During a train of stimuli, the growth of the secondary EPSPs in the CX cells led to a progressively increasing number of spikes per burst (up to two spikes).
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Figure 7. Comparison of augmenting responses in the thalamocortical (RE-TC-CX-IN) network evoked by intrathalamic (RE-TC) and prethalamic (TC only) stimulation. The responses to the first five stimuli are shown on the right on an expanded time scale. A, B, Two CX and two TC cells from an intact thalamocortical network during 10 Hz intrathalamic stimulation. CX cell responses have two components: the first EPSP is stereotyped, and the augmentation of the second EPSP depends on the position of the cell in the network. A, Far from the center of the network, the TC cell receives low-intensity stimulation and displays a weak augmenting response. The secondary EPSPs in the corresponding cortical cells were smaller, and the augmenting response was delayed. B, TC cells near the center of stimulation had strong augmenting responses that induced fast augmentation of CX responses during a train of stimuli. C, Two TC and two CX cells during weak prethalamic stimulation (gext = 0.145 µS). The stereotyped single-spike responses of TC cells elicited nonaugmenting EPSPs in CX cells. Open circles indicate the time of thalamic stimulation.
The second pair of TC-CX cells was located closer to the center of the network. More powerful stimulation led to action potentials starting from the first stimulus. Both CX and TC cells from this pair displayed stronger augmenting responses (up to four spikes in TC and up to three spikes in CX cells) compared with the cells from the first pair (up to three spikes in TC and up to two spikes in CX cells).
The train of stimuli was followed by a few cycles of slow oscillations at ~3 Hz. These oscillations were of thalamic origin (for details, see Bazhenov et al., 1998
Comparison of the low-threshold augmenting responses displayed by TC cells in an intact thalamocortical (RE-TC-CX-IN) network and after removal of the cortical (CX-IN) population revealed that the augmenting responses were weaker after "decortication" (Bazhenov et al., 1998
Stereotyped responses in a chain of RE-TC-CX-IN cells in response to prethalamic stimulation of the projection pathways
The responses of the RE-TC-CX-IN network to intrathalamic stimulation are shown in Figures 6 and 7, A, and B. To model a stimulus, AMPA receptors were activated simultaneously on RE and TC cells at 100% intensity and CX-IN cells at 10% intensity. A train of stimuli produced augmenting responses in TC and CX cells in good agreement with the in vivo data (Fig. 3).
In contrast, after 10 Hz prethalamic brachium conjunctivum stimulation in vivo, VL cells displayed monosynaptic responses and only an occasional fast spikes (Fig. 2). Simultaneous recording from CX cells in area 4 revealed EPSPs with variable amplitude and no augmentation during the entire train of stimuli.
The effects of prethalamic stimulation on a chain of RE-TC-CX-IN cells were modeled by low-intensity stimulation of TC cells alone. Figure 7C shows the responses of two TC-CX pairs from the chain. The TC cells displayed stereotyped single-spike responses during the entire train of stimuli. The lack of augmentation can be explained by weak one- or two-spike responses in the RE cells, which were unable to elicit the GABAB IPSPs in TC cells. The nonaugmented responses of TC cells evoked almost stereotyped EPSPs in the CX. In comparison, AMPA stimuli delivered simultaneously to TC and RE cells with the same low amplitude led to weak but augmenting responses in TC and CX cells (data not shown). Thus, the absence of RE stimulation at low intensities could explain the absence of augmenting responses both in TC and CX cells (Bazhenov et al., 1998
Augmenting responses in a chain of RE-TC-CX-IN cells in response to cortical stimulation
Repetitive thalamic stimulation results in augmenting responses of CX and IN cells because of the enhancement of TC-evoked EPSPs in these cells. Based on these results, repetitive cortical stimulation in the presence of a CX
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Figure 8. Thalamocortical augmenting responses in a chain of 24 × 4 RE-TC-CX-IN cells in response to cortical stimulation of both the CX and IN cells. A, 10 Hz train of stimuli for 1 sec. The intensity of stimulation was maximal at the center of the network and decayed exponentially with distance from the center. B, Expanded traces from A between t =
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Figure 9. Comparison of augmenting responses in the thalamocortical network (RE-TC-CX-IN) in response to cortical stimulation and comparison with an isolated cortical network (CX-IN). The responses to the first five stimuli are shown on the right on an expanded time scale. Two CX and two TC cells from intact an thalamocortical network during 10 Hz stimulation are shown. A, Direct cortical stimulation evoked single-spike responses in the CX cells far from the center of the network. B, Responses of a CX cell near the center of the network. Augmentation of the TC responses produced a growing secondary EPSP in the cortical cell and additional fast spike. C, Stereotyped responses of the same CX cells after removing the thalamic (RE-TC) network. Filled circles indicate the time of cortical stimulation.
The stimulation of cortical AMPA responses in CX and IN cells resulted first in one to three spike responses in the CX cells. Activation of CX
The strength of the cortical augmenting responses depends on the position of the cells relative to the center of stimulation. The CX cells near the center (Fig. 9B) displayed powerful (three-spike) responses to the stimulus-evoked EPSPs and augmentation up to four spikes during the train of stimuli. Another CX cell located near the boundary (Fig. 9A) obtained weaker stimulation from both the external electrode and TC cells and displayed weak augmenting responses (one or two spikes).
Mechanisms underlying augmenting responses in cortical neurons distant from the site of stimulation
Repetitive 10 Hz stimulation of the cortical cells (CX, IN) induced augmenting responses in these cells through corticothalamocortical (CX
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Figure 10. The influence of the CX-TC-CX loop on the augmenting responses in cortical neurons distant from the site of stimulation. Repetitive 10 Hz stimulation of half of the cortical network (CX-IN cells from 1-13) produced augmenting responses of the CX cells from the second half of the cortical network: A, CX cell 15; B, CX cell 16; C, CX cell 17. Responses from an intact thalamocortical model shown on the left. Secondary EPSPs in CX cells were from activation of the lateral (CX
In both networks, the CX cells displayed secondary EPSPs starting from the second stimulus in the train. These EPSPs arose from the CX
These results show how the thalamic network, through the activation of TC cells, could produce augmenting responses in spatially distant cortical areas.
The impact of progressive disfacilitation on cortical augmenting responses
TC cells recorded in vivo in anesthetized animals are hyperpolarized in comparison with the awake state, which reduces their tonic firing, but they nonetheless fire action potentials (Contreras and Steriade, 1995
Figure 11 shows the responses of three CX and three related TC cells drawn from a thalamocortical network. The first TC cell (Fig. 11A) was depolarized and fired spontaneously before the stimulation began. The membrane potential of the CX cells before stimulation was approximately
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Figure 11. Thalamocortical augmenting responses during a train of 10 Hz stimuli in the presence of spontaneous TC-evoked depolarization of the cortical network. Both RE and TC cells were stimulated. A, CX and TC cells far from the center of stimulation. B, CX and TC cells at an intermediate distance. C, CX and TC cells close to the center of stimulation. The EPSPs is the CX cells augmented despite hyperpolarization from disfacilitation of the spontaneous TC-evoked depolarization that began before the train of stimuli. Open circles indicate the time of thalamic stimulation (gAMPA = 0.1 µS between CX cells, gAMPA = 0.1 µS from CX to IN, gAMPA = 0.1 µS from CX to TC, gAMPA = 0.2 µS from CX to RE, gGABAA = 0.03 µS from IN to CX, gAMPA = 0.05 µS from TC to CX, and gAMPA = 0.03 µS from TC to IN).
The second thalamic stimulus evoked an even larger RE-evoked hyperpolarization in the TC cells, which produced low-threshold augmenting responses in some cells (Fig. 11C). The growth of TC-evoked EPSPs was sufficiently rapid to elicit an augmenting response in CX cells despite the tonic hyperpolarization. This effect was larger in CX cells near the center of the network (Fig. 11C) than in cells near the boundary (Fig. 11A). As a consequence of the progressive hyperpolarization of all of the TC cells during the train of stimuli, spontaneous firing ceased after the train, and the membrane potentials of the CX cells were lower than before the stimulation.
Influence of intracortical synaptic conductances on augmenting responses
The previous results from the simple circuit of four RE-TC-CX-IN cells demonstrated that the cortical network affects the development of cortical augmenting responses through intrinsic mechanisms. These results need to be confirmed in the chain of coupled RE-TC-CX-IN cells, and the influence of intracortical and thalamocortical synaptic conductances needs to be more closely examined.
Figure 12 shows the response of one arbitrarily selected pair of CX-IN cells during repetitive 10 Hz stimulation of RE-TC cells at 100% intensity and CX-IN cells at 10% intensity. The augmenting responses of the CX cell with "standard" values of synaptic conductances are shown in Figure 7A. In the four-cell RE-TC-CX-IN network, increase of the maximal conductance for the afferent TC
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Figure 12. Effect of the intracortical synaptic connections on the augmenting responses in cortical cells. One CX-IN pair from a network of 27 × 4 cells is shown during repetitive 10 Hz stimulation. Parameters are the same as in Figure 7A except as noted below. A, Increase of TC-evoked EPSPs in CX and IN cells produced enhancement of the cortical augmenting responses (compare A, Fig. 7A) (gAMPA = 0.15 µS from TC to CX cells). B, Enhancement of the lateral excitation evoked strong depolarization in the CX cell after the fifth stimulus and transformed the CX responses to tonic firing (gAMPA = 0.15 between CX cells). C, Increase of CX evoked EPSPs in IN cells enhanced responses in these cells and reduce augmenting responses in CX cells (gAMPA = 0.15 µS from CX to IN cells). D, Weak GABAB inhibition progressively hyperpolarized the CX cells after four or five shocks. This weakened the augmenting responses in CX cells (compare D, Fig. 7A) (gGABAB = 0.01 µS from IN to CX cells). Open circles indicate the time of thalamic stimulation.
The influence of lateral AMPA excitation between CX cells is shown in Figure 12B. Increasing the maximal conductance of AMPA CX
The influence of synaptic interconnections between CX and IN cells on augmenting responses is shown in Figs. 12, C and D, and 13. The strong increase in the CX
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Figure 13. Influence of intracortical IN
Although GABAB IPSPs are prominent in neocortical slice preparations (Avoli, 1986
Altering the synaptic conductances of most cortical synapses affected the augmenting responses in the cortical cells by adding or removing a few spikes from CX-IN responses. The only exception so far has been the depolarization and tonic firing of CX cells caused by an increase in the excitatory lateral CX
The strong enhancement of the augmenting response of CX neurons in this simulation was a consequence of the lateral CX
The shift of the balance between IN-evoked inhibition and CX-evoked excitation toward excitation changed the character of the poststimulus slow oscillations. The duration of the oscillations doubled from <1 sec in the original model (Fig. 7A) to nearly 2 sec (Figs. 12A, 13), whereas the TC-evoked EPSPs in CX cells became crowned with Na+ spikes. When the afferent TC
Augmenting responses in a thalamocortical model with three types of cortical cells
In the standard cortical model there are only two layers of cortical cells: excitatory regular-spiking cells and inhibitory fast-spiking cells in which the cortical CX cells receive inputs from TC cells and project back to both the RE and TC cells. Repetitive thalamic stimulation resulted in a gradual increase in the number of spikes per burst in the CX and IN cells. Consider now a cortical network with two layers of cortical excitatory cells and one layer of inhibitory cells. The cortical cells in the first excitatory layer (CX1), which corresponded with layer 4 of cortex, received inputs from TC cells and had AMPA synapses on IN cells and on the excitatory cells of the second layer (CX2), which projected back to RE and TC cells and corresponded to corticofugal cells in layer 6. The IN cells provide GABAA feedback inhibition to the CX1 ("input") cells and feedforward inhibition for the CX2 ("output") cells.
Figure 14 shows the responses of two cortical cells from different excitatory layers of a chain of coupled RE-TC-CX1-CX2-IN cells during repetitive 10 Hz thalamic stimulation. Both CX1 and CX2 cells displayed gradual augmenting responses. However, augmentation was much stronger for the CX1 cell in the input layer (from zero to three spikes) than for the CX2 cell of the output layer (from zero to one spike) because the feedforward IN-evoked inhibition reduced the CX1-evoked EPSPs in output layer. The burst discharges in TC cells evoked simultaneous AMPA EPSPs in CX1 and IN cells. IN-evoked GABAA IPSPs arrived at the CX1 cells with one synaptic delay and reduced the length of the spike bursts in these cells (see previous section). However, the same IPSPs arrived at the deep layer simultaneously with CX1-evoked EPSPs and had a much stronger inhibitory effect on CX2 cells than on CX1 cells. This model predicts a rapid buildup of powerful augmenting responses in deep layers of the cortex compared with superficial layers (Castro-Alamancos and Connors, 1996a
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Figure 14. Augmenting responses in a thalamocortical network model that included two layers of cortical cells. One pair of cortical cells from the two layers and one TC cell are shown during 10 Hz cortical stimulations. CX1 is an input cell receiving direct TC connections, and CX2 is an output cell sending connections to the thalamus. The CX2 cell had a reduced augmenting response compared with the CX1 cells because of the feedforward IN-evoked inhibition. Open circles indicate the time of thalamic stimulation (gAMPA = 0.1 µS between CX1 cells and CX2 cells, gAMPA = 0.1 µS from CX1 to CX2 and from CX2 to CX1, gAMPA = 0.03 µS from CX1 to IN and from CX2 to IN, gGABAA = 0.06 µS from IN to CX1 and IN to CX2, gAMPA = 0.1 µS from CX2 to TC, gAMPA = 0.2 µS from CX2 to RE, gAMPA = 0.11 µS from TC to CX1, and gAMPA = 0.03 µS from TC to IN).
Augmenting responses in a two-dimensional thalamocortical network
The one-dimensional chain of RE-TC-CX-IN cells used in previous simulations may not capture the dynamics of neurons arranged in two-dimensional sheets, as found in the cortex. Here we study a two-dimensional four-layer network consisting of 27 × 27 arrays of RE, TC, CX, and IN cells.
Repetitive 10 Hz intrathalamic stimulation produced augmenting responses in the two-dimensional model. The average membrane potential between two consequent stimuli (
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Figure 15. Thalamocortical augmenting responses in a two-dimensional thalamocortical network with 27 × 27 × 4 RE-TC-CX-IN cells in response to thalamic stimulation. Both RE and TC cells were stimulated at 100% of maximal intensity, and the CX-IN cells were stimulated with 10% of maximal intensity by the train of eight shocks (gAMPA = 0.1 µS between CX cells). The intensity of stimulation was maximal at the center of the network and decayed exponentially with distance from the center. Each panel displays the average depolarization
Secondary EPSPs in the CX cells were preceded by spike bursts in the TC cells (data not shown), which displayed a low-threshold intrathalamic augmenting response that accounted for the enhancement of the CX responses. There was a direct link between the strengths of the augmenting responses in the CX and TC cells. The variability in the parameters of the TC and RE cells accounted for the heterogeneity of the observed TC activity, which was the source of heterogeneity for the CX responses.
In both the TC and CX cells the strength of the augmenting responses depended on the distance of a cell from the center of stimulation. The cells located close to the center of stimulation displayed faster augmentation during repetitive stimulation compared with the delayed augmenting responses at the boundary cells. Note that the action potentials made only a small contribution to the values of
Thus, the two-dimensional model displayed augmenting responses during repetitive stimulation that were qualitatively similar to the one-dimensional model, suggesting that augmenting responses occur independently of the detailed patterns of connectivity.
DISCUSSION
Cortical augmenting responses during repetitive thalamic stimulation
In vivo recordings from the sensory and motor cortices of cats under barbiturate or ketamine-xylazine anesthetic have revealed that cortical augmenting responses during repetitive stimulation of the dorsal thalamus were preceded by low-threshold augmenting spike bursts in TC cells (Steriade et al., 1998
The low-threshold intrathalamic augmenting response in the model during repetitive RE-TC stimulation depended on the hyperpolarization of the TC cells by RE-evoked IPSPs, which deinactivated the low-threshold Ca2+ current in TC cells and enhanced the LTSs. Burst discharges in TC cells activated the TC
Although the intrathalamic mechanism that generated the cortical augmenting responses was highly robust to the parameters governing intracortical interactions, the pattern of augmenting responses depended strongly on the balance between IN-evoked inhibition and CX-evoked excitation in the CX cells. A shift toward excitation transformed the spike bursts in CX neurons from well separated bursts to more powerful burst discharges riding on a slow wave of depolarization and to tonic firing after several shocks (Figs. 12, 13).
Intracellular recordings from cortical cells during augmenting responses evoked by thalamic or cortical stimuli in vivo often show a hyperpolarization starting from the first stimulus in the train, which is the result of GABAA IPSPs and disfacilitation (Contreras et al., 1996
Prethalamic stimulation of the projection pathways
Consistent with the absence of spindles when prethalamic stimuli are used, compared with the powerful spindle oscillations evoked by corticothalamic stimulation (Steriade et al., 1972
Cortical augmenting responses during repetitive cortical stimulation
In vivo recordings from cortical neurons of anesthetized cats have revealed augmenting responses during repetitive cortical stimulation (Steriade et al., 1998
There are other purely intracortical mechanisms that may contribute to the augmenting responses of CX cells in the intact cortical network. Our recent intracellular recordings from intact cortex and isolated cortical slabs in cats under ketamine-xylazine or barbiturate anesthesia demonstrate a slight increase of the secondary, slow depolarization and associated spikes during rhythmic stimuli at 10 Hz (M. Steriade, I. Timofeev, and F. Grenier, unpublished data) (Dürmüller et al., 1998
Post-stimulus oscillations
The network model had a tendency to continue with a few cycles of the slow (~3 Hz) oscillations after a train of stimuli (Bazhenov et al., 1998
Although the origin of the slow poststimulus oscillation in the cortex is intrathalamic, the cortex enhances them through mechanisms similar to those that are involved in the generation of spindles (Contreras and Steriade, 1996
The balance between intracortical IN-evoked inhibition and CX-evoked excitation controls not only the augmenting responses during repetitive stimulation but also the slow poststimulus oscillations. A shift toward excitation by either increased excitatory inputs or disinhibition may transform the oscillations to long-lasting paroxysmal responses. The prolonged duration of the poststimulus oscillations shows that the cortex can contribute to the maintenance of synchronized epileptic-like slow oscillations in the thalamocortical network.
Predictions of the models
The thalamocortical network model of augmenting responses analyzed here makes several predictions that can be experimentally tested. First, if the intrathalamic low-threshold mechanism for cortical augmenting responses is correct, then augmentation in cortical pyramidal cells and inhibitory interneurons should occur simultaneously. Second, repetitive cortical stimulation in the model resulted in augmenting responses both locally and in remote areas of the cortical network because of the CX
FOOTNOTES Received Feb. 18, 1998; revised May 11, 1998; accepted May 29, 1998.
This research was supported by Human Frontier Science Program, The Howard Hughes Medical Institute, The Sloan Center for Theoretical Neurobiology, The Medical Research Council of Canada, and the Savoy Foundation.
Correspondence should be addressed to Maxim Bazhenov, The Howard Hughes Medical Institute, The Salk Institute, Computational Neurobiology Laboratory, 10010 North Torrey Pines Rd., La Jolla, CA 92037.
REFERENCES
- Avoli M (1986) Inhibitory potentials in neurons of the deep layers of the in vitro neocortical slices. Brain Res 370:165-170[Web of Science][Medline].
- Bal T, McCormick DA (1996) What stops synchronized thalamocortical oscillations? Neuron 17:297-308[Web of Science][Medline].
- Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (1998) Cellular and network models for intrathalamic augmenting responses during 10 Hz stimulation. J Neurophysiol 79:2730-2748
[Abstract/Free Full Text] .- Castro-Alamancos MA, Connors BW (1996a) Spatiotemporal properties of short-term plasticity in sensorimotor thalamocortical pathways of the rat. J Neurosci 16:2767-2779
[Abstract/Free Full Text] .- Castro-Alamancos MA, Connors BW (1996b) Cellular mechanisms of the augmenting response: short-term plasticity in a thalamocortical pathway. J Neurosci 16:7742-7756
[Abstract/Free Full Text] .- Connors BW, Malenka RC, Silva LR (1988) Two inhibitory postsynaptic potentials, and GABAa and GABAb receptor-mediated responses in neocortex of rat and cat. J Physiol (Lond) 406:443-468
[Abstract/Free Full Text] .- Contreras D, Steriade M (1995) Cellular basis of EEG slow rhythms
- Contreras D, Steriade M (1996) Spindle oscillations in a cats: the role of cortico-thalamic feedback in thalamically generated rhythms. J Physiol (Lond) 490:159-180
[Abstract/Free Full Text] .- Contreras D, Curró Dossi R, Steriade M (1993) Electrophysiological properties of cat reticular thalamic neurones in vivo. J Physiol (Lond) 470:273-294
[Abstract/Free Full Text] .- Contreras D, Timofeev I, Steriade M (1996) Mechanisms of long-lasting hyperpolarization underlying slow sleep oscillations in cat corticothalamic network. J Physiol (Lond) 494:251-264
[Abstract/Free Full Text] .- Contreras D, Destexhe A, Sejnowski TJ, Steriade M (1997) Spatiotemporal patterns of spindle oscillations in cortex and thalamus. J Neurosci 17:1179-1196
[Abstract/Free Full Text] .- Crunelli V, Haby M, Jassik-Gerschenfeld D, Leresche N, Pirchio M (1998) Cl- and K+-dependent inhibitory postsynaptic potentials evoked by interneurones of the rat lateral geniculate nucleus. J Physiol (Lond) 399:153-176
[Abstract/Free Full Text] .- Destexhe A, Contreras D, Sejnowski TJ, Steriade M (1994a) A model of spindle rhythmicity in the isolated thalamic reticular nucleus. J Neurophysiol 72:803-818
[Abstract/Free Full Text] .- Destexhe A, Mainen ZF, Sejnowski TJ (1994b) Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. J Comp Neurosci 1:195-230[Medline].
- Destexhe A, Bal T, McCormick DA, Sejnowski TJ (1996a) Ionic mechanisms underlying synchronized oscillations and propagating waves in a model of ferret thalamic slices. J Neurophysiol 76:2049-2070
[Abstract/Free Full Text] .- Destexhe A, Contreras D, Steriade M, Sejnowski T, Huguenard JR (1996b) In vivo, in vitro, and computational analysis of dendritic calcium currents in thalamic reticular neurons. J Neurosci 16:169-185
[Abstract/Free Full Text] .- Dürmüller N, Timofeev I, Grenier F, Steriade M (1998) Mechanisms of intracortical augmenting responses. Soc Neurosci Abstr, in press.
- Dutar P, Nicoll RA (1998) A physiological role for GABAB receptors in the central nervous system. Nature 332:156-158.
- Enright WH, Higham DJ, Owren B, Sharp PW (1995) A survey of the explicit Runge-Kutta method. Available from ftp://ftp.cs.toronto.edu/ pub/reports/na/cs-94-291.ps.Z.
- Ferster D, Lindström S (1985) Augmenting responses evoked in area 17 of the cat by intracortical axonal collaterals of cortico-geniculate cells. J Physiol (Lond) 367:217-232
[Abstract/Free Full Text] .- Hernández-Cruz A, Pape HC (1989) Identification of two calcium currents in acutely dissociated neurons from the rat lateral geniculate nucleus. J Neurophysiol 61:1270-1283
[Abstract/Free Full Text] .- Hirsch JC, Burnod Y (1987) A synaptically evoked late hyperpolarization in the rat dorsolateral geniculate nucleus in vitro. Neuroscience 23:457-468[Web of Science][Medline].
- Hodgkin AL, Huxley AF (1952) A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol (Lond) 117:500-544.
- Houweling AR, Bazhenov M, Timofeev I, Steriade M, Sejnowski TJ (1998) Computational models of intracortical augmenting responses. Soc Neurosci Abstr, in press.
- Huguenard JR, McCormick DA (1992) Simulation of the currents involved in rhythmic oscillations in thalamic relay neurons. J Neurophysiol 68:1373-1383
[Abstract/Free Full Text] .- Huguenard JR, Prince DA (1992) A novel T-type current underlies prolonged Ca2+-dependent burst firing in GABAergic neurons of rat thalamic reticular nucleus. J Neurosci 12:3804-3817[Abstract].
- Huguenard JR, Prince DA (1994) Intrathalamic rhythmicity studied in vitro: nominal T-current modulation causes robust anti-oscillatory effects. J Neurosci 12:3804-3817.
- Huguenard JR, Coulter DA, McCormick DA (1991) A fast transient potassium current in thalamic relay neurons: kinetics of activation and inactivation. J Neurophysiol 66:1305-1315.
- Jahnsen H, Llinás R (1984a) Electrophysiological properties of guinea-pig thalamic neurones: an in vitro study. J Physiol (Lond) 349:205-226
[Abstract/Free Full Text] .- Jahnsen H, Llinás R (1984b) Ionic basis for electro responsiveness and oscillatory properties of guinea-pig thalamic neurones in vitro. J Physiol (Lond) 349:227-247
[Abstract/Free Full Text] .- Jones EG (1985) In: The thalamus. New York: Plenum.
- Kammermeier PJ, Jones SW (1997) High-voltage-activated calcium currents in neurons acutely isolated from the ventrobasal nucleus of the rat thalamus. J Neurophysiol 77:465-475
[Abstract/Free Full Text] .- Kandel A, Buzsáki G (1997) Cellular-synaptic generation of sleep spindles, spike-and-wave discharges, and evoked thalamocortical responses in the neocortex of the rat. J Neurosci 17:6783-6797
[Abstract/Free Full Text] .- Leresche N, Lightowler S, Soltesz I, Jassik-Gerschenfeld D, Crunelli V (1991) Low-frequency oscillatory activities intrinsic to rat and cat thalamocortical cells. J Physiol (Lond) 441:155-174
[Abstract/Free Full Text] .- Lüthi A, McCormick DA (1997) Both electrophysiological and biochemical oscillations determine spindle wave periodicity. Soc Neurosci Abstr 23:708.
- Mainen Z, Sejnowski TJ (1994) Influence of dendritic structure on firing patterns in model neocortical neurons. Nature 382:363-366.
- McCormick DA, Huguenard JR (1992) A model of the electrophysiological properties of thalamocortical relay neurons. J Neurophysiol 68:1384-1400
[Abstract/Free Full Text] .- McCormick DA, Pape HC (1990) Properties of a hyperpolarization-activated cation current and its role in rhythmic oscillation in thalamic relay neurons. J Physiol (Lond) 431:291-318
[Abstract/Free Full Text] .- Metherate R, Ashe JH (1994) Facilitation of NMDA receptor-mediated EPSP by paired-pulse stimulation in rat neocortex via depression of GABAergic IPSPs. J Physiol (Lond) 484:331-348
[Abstract/Free Full Text] .- Morin D, Steriade M (1981) Development from primary to augmenting responses in primary somatosensory cortex. Brain Res 205:49-66[Web of Science][Medline].
- Morison RS, Dempsey EW (1943) Mechanisms of thalamocortical augmentation and repetition. Am J Physiol 138:297-308
[Free Full Text] .- Paré D, Curró Dossi R, Steriade M (1991) Three types of inhibitory postsynaptic potentials generated by interneurons in the anterior thalamic complex of cat. J Neurophysiol 66:1190-1204
[Abstract/Free Full Text] .- Pedroarena C, Llinás R (1997) Dendritic calcium conductances generate high-frequency oscillation in thalamocortical neurons. Proc Natl Acad Sci USA 94:724-728
[Abstract/Free Full Text] .- Soltesz I, Lightowler S, Leresche N, Jassik-Gerschenfeld D, Pollard CE, Crunelli V (1991) Two inward currents and the transformation of low-frequency oscillations of rat and cat thalamocortical cells. J Physiol (Lond) 441:175-197
[Abstract/Free Full Text] .- Steriade M (1984) The excitatory-inhibitory response sequence of thalamic and neocortical cells: state related changes and regulatory systems. In: Dynamic Aspects of Neocortical Function (Edelman GM, Gall WE, Cowan WM, eds), pp 107-157. New York: Wiley.
- Steriade M, Timofeev I (1997) Short-term plasticity during intrathalamic augmenting responses in decorticated cats. J Neurosci 17:3778-3795
[Abstract/Free Full Text] .- Steriade M, Wyzinski P, Apostol V (1972) Corticofugal projections governing rhythmic thalamic activity. In: Corticothalamic Projections and Sensorimotor Activities (Frigyesi TL, Rinvik E, Yahr MD, eds), pp 221-272. New York: Raven Press.
- Steriade M, Domich L, Oakson G (1986) Reticularis thalami neurons revisited: activity changes during shifts in states of vigilance. J Neurosci 6:68-81[Abstract].
- Steriade M, Curró Dossi R, Nuñez A (1991) Network modulation of a slow intrinsic oscillation of cat thalamocortical neurons implicated in sleep delta waves: cortical potentiation and brainstem cholinergic suppression. J Neurosci 11:3200-3217[Abstract].
- Steriade M, Nunez A, Amzica F (1993a) A novel slow (<1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J Neurosci 13:3252-3265[Abstract].
- Steriade M, Nunez A, Amzica F (1993b) Intracellular analysis of relations between the slow (<1 Hz) neocortical oscillation and other sleep rhythms of the electroencephalogram. J Neurosci 13:3266-3283[Abstract].
- Steriade M, Contreras D, Curró Dossi R, Nunez A (1993c) 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[Abstract].
- Steriade M, Timofeev I, Grenier F, Dürmüller N (1998) Role of thalamic and cortical neurons in augmenting responses and self-sustained activity: dual intracellular recordings in vivo. J Neurosci 18:6425-6443
[Abstract/Free Full Text] .- Timofeev I, Steriade M (1996) The low-frequency rhythms in the thalamus of intact-cortex and decorticated cats. J Neurophysiol 76:4152-4168
[Abstract/Free Full Text] .- Timofeev I, Steriade M (1997) Fast (20-40 Hz) oscillations in cat cerebellothalamic pathway and their synchronization with cortical potentials. J Physiol (Lond) 504:153-168
[Abstract/Free Full Text] .- Timofeev I, Steriade M (1998) Intrathalamic mechanisms of incremental responses in reticular and relay cells. J Neurophysiol 79:2716-2729
[Abstract/Free Full Text] .- Timofeev I, Contreras D, Steriade M (1996) Synaptic responsiveness of cortical and thalamic neurones during various phases of slow sleep oscillation in cat. J Physiol (Lond) 494:265-278
[Abstract/Free Full Text] .- Traub RD, Miles R (1991) In: Neuronal networks of the hippocampus. Cambridge, UK: Cambridge UP.
- Ulrich D, Huguenard JR (1997) Nucleus-specific chloride homeostasis in rat thalamus. J Neurosci 17:2348-2354
[Abstract/Free Full Text] .- Zhou Q, Godwin DW, O'Malley DH, Adams PR (1997) Visualization of calcium influx through channels that shape the burst and tonic firing modes of thalamic relay cells. J Neurophysiol 77:2816-2825
[Abstract/Free Full Text] .
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