Minimal alterations in T-type calcium channel gating markedly modify physiological firing dynamics.

T-type calcium channel isoforms expressed in heterologous systems demonstrate marked differences in the biophysical properties of the resulting calcium currents. Such heterogeneity in gating behaviour not only reflects structural differences but is also observed following the regulation of channel activity by a number of ligands. However, the physiological impact of these differences in gating parameters of the T channels has never been evaluated in situ where the unique interplay between T-type calcium and other intrinsic currents is conserved, and T channel activation can be triggered by synaptic stimulation. Here, using the dynamic clamp technique, artificial T conductances were re-incorporated in thalamic neurons devoid of endogenous T currents to dissect the physiological role of the T current gating diversity on neuronal excitability. We demonstrate that the specific kinetics of the T currents in thalamocortical and nucleus reticularis thalami neurons determine the characteristic firing patterns of these neurons. We show that subtle modifications in T channel gating that are at the limit of the resolution achieved in classical biophysical studies in heterologous expression systems have profound consequences for synaptically evoked firing dynamics in native neurons. Moreover, we demonstrate that the biophysical properties of the T current in the voltage region corresponding to the foot of the activation and inactivation curves drastically condition physiologically evoked burst firing with a high degree of synaptic input specificity.

Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents.

The sensitivity to GABA of Purkinje cells in thin cerebellar slices was examined by recording either spontaneous inhibitory synaptic currents or ionic currents elicited by local GABA applications. The effects of Ca2+ entry induced by depolarizing voltage pulses were opposite for the two types of currents. Currents due to exogenous GABA applications were increased by a train of voltage pulses. This potentiation was transient with an average half recovery period of 3.7 min. Spontaneous synaptic currents were reduced by depolarizing voltage pulses, with a half recovery time of about 20 s. The inhibition was largely explained by a decrease of the frequency of synaptic events, suggesting that the primary location of the effect was presynaptic. Thus, a Ca2+ rise increases the sensitivity of Purkinje cells to GABA and induces a retrograde inhibition of presynaptic terminals. The latter effect may be due to a diffusible Ca2(+)-dependent messenger.

A role for GABAB receptors in excitation and inhibition of thalamocortical cells.

Gamma-aminobutyric acid (GABA) in the thalamus has mainly been associated with the inhibitory modulation of the sensory and cortical flow of information via a 'classical', chloride-dependent, GABAA receptor-mediated action. However, the discovery of a late, long-lasting potassium-dependent inhibitory postsynaptic potential (IPSP) mediated by GABAB receptors present on thalamocortical cells, has allowed new insights into our understanding of the physiological role of this neurotransmitter. In particular, work on the dorsal lateral geniculate nucleus indicates that together with a relatively weak inhibition, GABAB receptor-mediated IPSPs 'prepare' thalamocortical cells for burst firing by activating low-threshold calcium potentials. Thus, GABA in the thalamus can no longer be viewed only as a 'classical' inhibitory transmitter but also as a neuromodulator with a 'priming' role for burst firing excitation. This dual role of GABAB receptors in inhibition and excitation of thalamocortical cells might allow different interpretations of earlier findings in animals and humans, both in healthy and pathological conditions. It will also help to identify new functions for postsynaptic GABAB receptors in other parts of the central nervous system.

Synaptic Currents in Thalamo-cortical Neurons of the Rat Lateral Geniculate Nucleus.

Thalamo-cortical neurons were identified in slices of the rat dorsal lateral geniculate nucleus and whole-cell currents were recorded using the patch-clamp technique. Postsynaptic currents occurring spontaneously, or elicited by extracellular stimulation in the vicinity of the recorded neuron, were analysed. Spontaneous postsynaptic currents were observed in every recorded neuron. At a holding potential of - 60 mV, and with a high internal Cl-, the currents were inward and had amplitudes ranging from < 10 to 425 pA. All the spontaneous currents were blocked by 10 microM bicuculline, indicating that they were due to the activation of postsynaptic gamma-aminobutyric acid (GABAA) receptors. The 10-90% rise time of these spontaneous GABAergic currents was 0.86 +/- 0.19 ms. Their time course of decay could be fitted to an exponential function with one time constant of 18.19 +/- 3.02 ms (mean +/- SD), or two time constants of 4.47 +/- 0.77 and 33.27 +/- 3.74 ms. This activity was frequently organized in bursts. Stimulus-evoked postsynaptic currents were recorded and shown to be due to the activation of glutamatergic receptors. Under similar experimental conditions a bicuculline-sensitive component was also recorded. These stimulus-evoked GABAergic currents had a 10 - 90% rise time of 1.93 +/- 0.54 ms. Their time course of decay could also be fitted to an exponential function with one time constant of 24.42 ms or two time constants of 10.26 +/- 2.46 and 49.30 +/- 10.98 ms. The difference in the time course between spontaneous and evoked GABAergic currents suggests that these responses may arise from synapses having different locations.

Morphology and laminar distribution of electrophysiologically identified cells in the pigeon's optic tectum: an intracellular study.

The responses of 65 cells to electrical stimulation of the contralateral optic nerve were intracellularly recorded in the pigeon optic tectum by using micropipettes filled with a solution of horseradish peroxidase. Nineteen of them were successfully labeled. Microscopic examination of the filled cells shows that our sample includes six pyramidal, ten ganglion, two stellate, and one bipolar horizontal cells. Thus, pyramidal and ganglion neurons constitute the most numerous types of cells in our sample. Pyramidal cells were located in layer II but mostly in its non-retinorecipient part, and they had restricted ascending dendritic trees oriented orthogonal to the tectal lamination. Ganglion cells were located in layer III with one exception, which was in sublayer IIi. These cells had non-oriented dendritic trees which ramify over considerable distances. Terminal dendritic branches from a number of pyramidal and ganglion cells extended superficially well within the region of optic fibers termination. In our study, ganglion cells constituted the efferent tectal elements. Pyramidal cells responded to optic nerve stimulation with a pure EPSP, with an EPSP-IPSP sequence, or with a pure IPSP. Ganglion cells always exhibited an IPSP either alone or preceded by an EPSP. Stellate and bipolar cells responded with a pure EPSP. The study of the laminar distribution of labeled and non-labeled cells shows from surface to depth, a gradual increase in the number of cells responding with an EPSP-IPSP or with a pure IPSP and a gradual decrease in the number of those exhibiting a pure EPSP. The analysis of the sensitivity of EPSPs and IPSPs to high frequency optic nerve stimulation shows that monosynaptic as well as polysynaptic EPSPs can be recorded from cells in the non-retinorecipient tectal region, a number of ganglion and pyramidal cells receive a direct retinal excitatory input as their dendrites pass through the region of optic endings, most IPSPs are polysynaptic, some cells located in the retinorecipient region may receive direct retinal inhibitory connections.

On the putative contribution of GABA(B) receptors to the electrical events occurring during spontaneous spike and wave discharges.

Cortical and thalamic neurones play a major role in the generation/expression of spike and wave discharges (SWDs), the main electroencephalographic (EEG) feature of absence seizures. The detailed mechanisms leading to this paroxysmal EEG activity, however, are still poorly understood. We have now made in vivo intracellular recordings from layer V cortical neurones of the facial motor cortex and from thalamocortical (TC) neurones of the ventroposteromedial and ventroposterolateral nuclei in a well established model of this disease: the Genetic Absence Epilepsy Rats from Strasbourg (GAERS). The main feature of the intracellularly recorded activity of TC neurones during spontaneous SWDs was the presence of rhythmic sequences of synaptic potentials consisting of an EPSP closely followed by 2-6 IPSPs. These rhythmic sequences were superimposed on a small tonic hyperpolarization that lasted for the whole duration of the SWD and was still present at potentials close to -85 mV. The rhythmic IPSPs, on the other hand, had a reversal potential of -68 mV, and always appeared as depolarizing events when recording with KCl-filled electrodes at -55 mV. Low frequency electrical stimulation of the corresponding cortical area evoked in TC neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. The main feature of the intracellular activity recorded in cortical neurones during spontaneous SWDs was the presence of rhythmic depolarizations. Their frequency was similar to the one of SWDs in the EEG, and was not affected by DC injection. The amplitude of the rhythmic depolarizations, however, increased following steady hyperpolarization of the neurone by DC injection. An increase in the apparent input resistance of cortical neurones was observed during SWDs compared to the inter-SWDs periods. Low frequency electrical stimulation of the contralateral striatum evoked in cortical neurones a short and a long lasting IPSP, whose waveforms were reminiscent of a GABA(A) and a GABA(B) IPSP, respectively. Our data indicate that there are no rhythmic GABA(B) IPSPs and low threshold Ca2+ potentials in GAERS TC neurones during SWDs, but rhythmic sequences of EPSP/IPSPs superimposed on a tonic hyperpolarization that might represent a long lasting GABA(B) IPSP. Further experiments are required to clarify the nature of the voltage waveform and the increase in input resistance observed in cortical neurones during spontaneous SWDs in GAERS.

On the properties and origin of the GABAB inhibitory postsynaptic potential recorded in morphologically identified projection cells of the cat dorsal lateral geniculate nucleus.

Intracellular recordings were performed from projection cells of the cat dorsal lateral geniculate nucleus in vitro to investigate the properties and origin of optic tract evoked inhibitory postsynaptic potentials mediated by GABAB receptors and their relationship to the physiologically different cell classes present in this nucleus. In all three main laminae of the dorsal lateral geniculate nucleus, stimulation of the optic tract evoked an excitatory postsynaptic potential followed by two inhibitory postsynaptic potentials. The first is a GABAA receptor mediated inhibitory postsynaptic potential since it was blocked by bicuculline, reversed in polarity following intracellular Cl- injection and had a reversal potential similar to the bicuculline sensitive hyperpolarizing effect of GABA. The second is a GABAB receptor mediated inhibitory postsynaptic potential. Its amplitude was not linearly related to membrane potential (maximal amplitude at -60 mV), it decreased when using frequencies of stimulation higher than 0.05 Hz and it was reversibly increased by addition of bicuculline to the perfusion medium. The reversal potential of GABAB inhibitory postsynaptic potentials was dependent on the extracellular K+ concentration but did not change in the presence of bicuculline or when recording with Cl- filled microelectrodes. While GABAA inhibitory postsynaptic potentials always abolished repetitive firing of projection cells, GABAB inhibitory postsynaptic potentials were able to block weak firing but unable to decrease strong activation of projection cells evoked by direct current injection. Optic tract evoked GABAB (as well as GABAA) inhibitory postsynaptic potentials could be recorded in slices which did not include the perigeniculate nucleus, thus indicating that they are generated by the interneurons of the dorsal lateral geniculate nucleus. Using intracellular injection of horseradish peroxidase, we have found that the GABAB inhibitory postsynaptic potentials are present in projection cells showing many different types of neuronal morphologies. In conclusion, GABA released from interneurons in the dorsal lateral geniculate nucleus is capable of evoking an early, short-lasting GABAA and a late, long-lasting GABAB inhibitory postsynaptic potential in projection cells with diverse morphology, indicating that the late inhibition in the dorsal lateral geniculate nucleus can no longer be associated exclusively with the recurrent inhibitory pathway through the perigeniculate nucleus.

Somatostatin inhibits GABAergic transmission in the sensory thalamus via presynaptic receptors.

The action of somatostatin on GABA-mediated transmission was investigated in cat and rat thalamocortical neurons of the dorsal lateral geniculate nucleus and ventrobasal thalamus in vitro. In the cat thalamus, somatostatin (10 microM) had no effect on the passive membrane properties of thalamocortical neurons and on the postsynaptic response elicited in these cells by bath or iontophoretic application of (+/-)baclofen (5-10 microM) or GABA, respectively. However, somatostatin (1-10 microM) decreased by a similar amount (45-55%) the amplitude of electrically evoked GABA(A) and GABA(B) inhibitory postsynaptic potentials in 71 and 50% of neurons in the lateral geniculate and ventrobasal nucleus, respectively. In addition, the neuropeptide abolished spontaneous bursts of GABA(A) inhibitory postsynaptic potentials in 85% of kitten lateral geniculate neurons, and decreased (40%) the amplitude of single spontaneous GABA(A) inhibitory postsynaptic potentials in 87% of neurons in the cat lateral geniculate nucleus. Similar results were obtained in the rat thalamus. Somatostatin (10 microM) had no effect on the passive membrane properties of thalamocortical neurons in this species, or on the outward current elicited by puff-application of (+/-)baclofen (5-10 microM). However, in 57 and 22% of neurons in the rat lateral geniculate and ventrobasal nuclei, respectively, somatostatin (1 microM) reduced the frequency, but not the amplitude, of miniature GABA(A) inhibitory postsynaptic currents by 31 and 37%, respectively. In addition, the neuropeptide (1 microM) decreased the amplitude of evoked GABA(A) inhibitory postsynaptic currents in 20 and 55% of rat ventrobasal neurons recorded in normal conditions and during enhanced excitability, respectively: this effect was stronger on bursts of inhibitory postsynaptic currents(100% decrease) than on single inhibitory postsynaptic currents (41% decrease). These results demonstrate that in the sensory thalamus somatostatin inhibits GABA(A)- and GABA(B)-mediated transmission via a presynaptic mechanism, and its action is more prominent on bursts of GABAergic synaptic currents/potentials.

Cortical-area specific block of genetically determined absence seizures by ethosuximide.

Absence epilepsy is characterised by a paroxysmal loss of consciousness, of abrupt onset and termination, and is associated with a bilateral synchronous spike and wave discharge (SWD) on the electroencephalogram. Absence seizures involve an interplay between thalamic and cortical structures, although most research has so far focussed on sensory thalamic nuclei and the reticular thalamic nucleus (RTN). Thus, microinfusion of ethosuximide (ETX), a first choice anti-absence drug, into either the ventrobasal thalamus or RTN of the genetic absence epilepsy rat from Strasbourg (GAERS), a validated rat model of absence epilepsy, does not produce immediate cessation of seizure activity, as is seen following systemic administration. As recent evidence indicates a seizure initiation site within the peri-oral region of the primary somatosensory cortex (S1po), we have now applied ETX into S1po as well as the somatosensory cortex forelimb region (S1FL) and the motor cortex (M1) of freely moving GAERS. Microinfusion of 10 or 20 nmol/side of ETX into S1po produced an immediate cessation of seizure activity. A less marked response was produced when even a higher dose (200 nmol/side) was infused into S1FL. No reduction of SWD was seen when ETX was infused into M1. Microinfusion of CGP 36742 (5 nmol/side), a GABA(B) antagonist, produced immediate cessation of seizure activity in both S1po and M1 and a delayed effect in S1FL. These data suggest that the ability of ETX to abolish genetically determined absence seizures is cortical-area specific and support the involvement of S1po in the initiation of SWDs.

Thalamic low threshold calcium current in a genetic model of absence epilepsy.

The low threshold calcium current (IT) in thalamo-cortical neurones contributes to the generation of spike and wave discharges (SWDs) characteristic of generalized, non-convulsive absence epilepsy. The biophysical properties of this current were analysed in dorsal lateral geniculate neurones from the Genetic Absence Epilepsy Rats from Strasbourg (GAERS+). No difference was found in the voltage dependence and kinetics of IT between GAERS+ and rats of the non epileptic control strain (GAERS-). Thus, a dysfunction of IT does not appear to underlie the occurrence of SWDs in absence epilepsy.

An in vitro slice preparation of the cat lateral geniculate nucleus.

A slice preparation of the cat thalamus containing the lateral geniculate nucleus and the terminal portion of the optic tract is described. Ultrastructurally the slices remain relatively normal for only a short time after cutting. Indeed most cellular elements deteriorate quickly with time but patches of relatively intact tissue were still present even 10 h after cutting and maintenance in a storage bath. However, for 4-5 h after cutting long-lasting intracellular recordings of high quality and stability were obtained, and intrasomatic injection of horseradish peroxidase used for the morphological identification of recorded neurones as X or Y cells.

Optic tract stimulation evokes GABAA but not GABAB IPSPs in the rat ventral lateral geniculate nucleus.

The inhibitory postsynaptic potentials (IPSPs) evoked in neurons of the rat ventral geniculate nucleus (vLGN) by electrical stimulation of the optic tract and the action of GABA and baclofen on the same cells were studied using intracellular recording technique in an in vitro slice preparation. A short latency short duration IPSP always followed the monosynaptic excitatory postsynaptic potential (EPSP). This IPSP reversed in polarity at about -65 mV and was reversibly blocked by bicuculline (50 microM) thus indicating that it represents a GABAA receptor-mediated IPSP. No long-lasting IPSP was evoked in vLGN cells by stimulation of the optic tract, while in the same slice, long-lasting GABAB IPSPs were routinely recorded in the dorsal lateral geniculate nucleus. GABA applied by ionophoresis evoked a hyperpolarization that had a reversal potential close to -70 mV and was antagonized by bicuculline. Baclofen hyperpolarized vLGN neurons and its action was reversibly blocked by the selective GABAB antagonist phaclofen (1 mM). In the presence of bicuculline GABA also produced a hyperpolarization that had properties similar to that evoked by baclofen. These results indicate that, although functional GABAA and GABAB receptors are present on vLGN neurons, stimulation of the optic tract evokes only GABAA but not GABAB mediated IPSPs. The lack of long-lasting GABAB IPSPs could explain the absence of long-lasting inhibition observed in vLGN neurons in vivo following stimulation of the optic tract.

Postsynaptic potentials in neurons of the pigeon's optic tectum in response to afferent stimulation from the retina and other visual structures: an intracellular study.

The responses of the cells in the pigeon's optic tectum to electrical stimulation of the contralateral optic nerve, the ipsilateral visual Wulst and the opposite optic tectum were intracellularly recorded. Optic nerve or visual Wulst stimulation elicited 3 types of responses: (1) a pure EPSP which gave rise to one or two action potentials; (2) an EPSP which sometimes gave rise to a spike, followed by an IPSP; and (3) a pure IPSP. Opposite tectum stimulation evoked in the tectal cells either a pure IPSP or a pure EPSP. The mono- or polysynaptic nature of the pathways involved in the excitatory and inhibitory responses of the tectal cells was assessed by increasing the frequency of the optic nerve stimulation. At low stimulus rates (2-6 Hz), all the excitatory events showing latencies longer than 5 ms were blocked suggesting that they were polysynaptic. Excitatory events having latencies shorter than 5 ms were generally able to follow high rate frequencies of optic nerve stimulation (40, 50 or 90 Hz) and we considered them to be monosynaptic. All but 3 IPSPs evoked by optic nerve stimulation, were blocked by stimulus rates beyond 5 Hz. Thus, although most IPSPs are generated through polysynaptic paths, direct retino-tectal inhibitory paths may also exist. The latency of the responses of individual cells to optic nerve, visual Wulst and opposite tectum stimulation show that the polysynaptic IPSPs to optic nerve stimulation did not involve relays in the visual Wulst or the opposite tectum.

The GABAB antagonist phaclofen inhibits the late K+-dependent IPSP in cat and rat thalamic and hippocampal neurones.

Phaclofen (0.5-1 mM) reversibly inhibited the late, bicuculline resistant, K+ dependent IPSP recorded in projection cells of the cat and rat dorsal lateral geniculate nucleus and in rat hippocampal CA1 pyramidal neurones. At the same concentrations, phaclofen reversibly blocked the K+ dependent, bicuculline insensitive hyperpolarization evoked by GABA and baclofen but had no effect on the GABAA IPSP. These results represent conclusive evidence that GABAB receptors mediate the late K+ dependent IPSP in cortical and subcortical neurones.

Receptive field properties of single cells in the pigeon's optic tectum during cooling of the 'visual wulst'.

In birds, efferents from the visual telencephalon (visual wulst) terminate in the ipsilateral and contralateral optic tectum. This study concerns the influence of a bilateral cryogenic block of the wulst on the receptive field properties of the visual tectal cells in the pigeon. Tectal units were tested for their responses to static and moving stimuli before, during and after cooling the wulst. For some units the cryogenic block of the wulst was repeated twice. The responsiveness to static and moving stimuli was decreased in most of the tectal cells when the neural activity of the wulst was blocked. In contrast, in some units cooling the wulst provokes an increase of responsiveness. These results indicate that the wulst-tectum path is able to convey both excitatory and inhibitory influences. Other receptive field properties such as the spatial location of the light and dark excitatory regions in the field, the effect of the surround, the size and shape of the excitatory region, the relative responsiveness to static and moving stimuli and the 'spontaneous activity' were not affected by wulst cooling. Directional tuning curves were obtained in 18 directionally selective cells before, during and after wulst cooling. In 6 of them the cryogenic block provoked a reduction in directional selectivity either by way of a reduction of the preferred response (4 cells) or by way of an increase of the non-preferred responses (2 cells). In two others directionally selective cells, cooling the wulst provoked a total loss of directional selectivity due to a reduction of the response to the preferred direction together with an increase of the response to the null direction. These results show: (1) that the retinal directional selective input to the tectum is affected by the cryogenic block of the wulst; and (2) that the visual wulst provokes a sharpening of the directional tuning at the optic tectum level.

X- and Y-cells identified in the cat lateral geniculate nucleus in vitro.

Using an in vitro preparation of the cat dorsal lateral geniculate nucleus, we have studied the passive membrane properties and the electrotonic structure of single cells each identified as X or Y on the basis of their morphological features following intrasomatic injection of horseradish peroxidase. The input resistance of X-cells is higher and the membrane time constant longer than of Y-cells. The electrotonic length and the dendritic to somatic conductance ratio are similar for both classes of neurones.

Synaptic transmission of excitation from the retina to cells in the pigeon's optic tectum.

Intracellular recordings were used to study the synaptic excitation of optic tectum neurons in the pigeon. Electrical stimulation of both contralateral optic nerve and ipsilateral optic tract evoked in the tectal neurons EPSPs which in most cases were followed by an IPSP. An extrapolation procedure based on response latency was used to reveal that the EPSPs were mediated by way of mono-, di- and polysynaptic connections with the retinal endings. The laminar location of the recorded cells was estimated according to the field potential and the recording depth with the exception of one cell which was intracellularly stained with HRP. Monosynaptic EPSPs were recorded from cells in the retinorecipient region (sublayers IIa-f) as well as in the non-retinorecipient region (sublayers IIg-j and layer III) of the tectum, while di- and polysynaptic EPSPs were never recorded from the input layers. Tectofugal projections arise largely from layer III neurons. Thus, these results indicate that retinal excitation is transmitted to the output tectal cells by way of mono-, di- or polysynaptic pathways. The conduction velocities of most retinal fibers mediating the EPSP ranged from 4 to 22 m/s (average 12 m/s). However, in a number of retinal fibers the conduction velocities were in a faster range, up to 36 m/s.

Synaptic organization of inhibitory circuits in the pigeon's optic tectum.

The synaptic organization of inhibitory systems in the pigeon's optic tectum was studied with intracellular recording techniques. An extrapolation procedure based on response latency was used to determine the synaptic delay of the postsynaptic potentials (PSPs) and the velocity of conduction of the associated retinal axons. Tectal cells receive mostly disynaptic, trisynaptic or polysynaptic inhibition from retinal ganglion cells. However, evidence was found which together with previous studies raised the possibility of the existence of a direct inhibitory retino-tectal path. Our present results also suggest that inhibition is transmitted from the retina to the tectal cells by way of both, feedforward and feedback pathways.

Pacemaker-like and other types of spontaneous membrane potential oscillations of thalamocortical cells.

During EEG-synchronized sleep, thalamic activity is characterized by rhythmic oscillations that till recently have been suggested to require the contribution of intra- and extra-thalamic inputs. The present experiments show that thalamocortical (TC) cells, mechanically and pharmacologically isolated from their intra-thalamic, cortical and brainstem inputs, are capable of different types of spontaneous membrane potential oscillations some of which resemble those observed in TC cells of the living animal during EEG-synchronization.

The properties of reticular thalamic neuron GABA(A) IPSCs of absence epilepsy rats lead to enhanced network excitability.

Both human investigations and studies in animal models have suggested that abnormalities in GABA(A) receptor function have a potential role in the pathophysiology of absence seizures. Recently we showed that, prior to seizure onset, GABA(A) IPSCs in thalamic reticular (NRT) neurons of genetic absence epilepsy rats from Strasbourg (GAERS) had a 25% larger amplitude, a 40% faster decay and a 45% smaller paired-pulse depression than those of nonepileptic control (NEC) rats. By means of a novel mathematical description, the properties of both GAERS and NEC GABAergic synapses can be mimicked. These model synapses were then used in an NRT network model in order to investigate their potential impact on the neuronal firing patterns. Compared to NEC, GAERS NRT neurons show an overall increase in excitability and a higher frequency and regularity of firing in response to periodic input signals. Moreover, in response to randomly distributed stimuli, the GAERS but not the NEC model produces resonance between 7 and 9 Hz, the frequency range of spike-wave discharges in GAERS. The implications of these results for the epileptogenesis of absence seizures are discussed.