Functional Dynamics of GABAergic Inhibition in the Thalamus

Abstract

The inhibitory gamma-aminobutyric acid-containing (GABAergic) neurons of the thalamic reticular and perigeniculate nuclei are involved in the generation of normal and abnormal synchronized activity in thalamocortical networks. An important factor controlling the generation of activity in this system is the amplitude and duration of inhibitory postsynaptic potentials (IPSPs) in thalamocortical cells, which depend on the pattern of activity generated in thalamic reticular and perigeniculate cells. Activation of single ferret perigeniculate neurons generated three distinct patterns of GABAergic IPSPs in thalamocortical neurons of the dorsal lateral geniculate nucleus: Low-frequency tonic discharge resulted in small-amplitude IPSPs mediated by GABAA receptors, burst firing resulted in large-amplitude GABAA IPSPs, and prolonged burst firing activated IPSPs mediated by GABAA and GABAB receptors. These functional properties of GABAergic inhibition can reconfigure the operations of thalamocortical networks into patterns of activity associated with waking, slow-wave sleep, and generalized seizures.

Spike-and-Wave Oscillations Based on the Properties of GABABReceptors

“…1 A2). The latter feature is consistent with the observation that GABA B responses appear only under high-intensity stimulus conditions (Dutar and Nicoll, 1988;Davies et al, 1990) and the evidence that bursts of high-frequency action potentials are an ideal presynaptic signal to evoke GABA B currents (Huguenard and Prince, 1994b;Kim et al, 1997). In the model this property is obtained from the fact that a sufficient level of G-proteins must be accumulated to evoke significant K ϩ current.…”

The initiation of bursts in thalamic neurons and the cortical control of thalamic sensitivity

“…There is evidence that inhibitory synapses are distributed all through the dendrites of relay cells (Liu et al 1995;Kim et al 1997 how these dendritic conductances affect rebound burst generation, we used a model with dendritically located I T (see above), together with a uniform distribution of GABA A receptors on the dendrites (see § 2). As expected from the voltage dependence of I T , and the negative reversal potential of fast inhibition in relay cells (295 mV in Ulrich & Huguenard 1997), rebound bursts can only be obtained within a given range of membrane potentials and IPSP amplitudes, as shown in gure 2.…”

“…For an estimated quantal conductance of GABA A synapses of 300 pS (Cox et al 1997;Le Feuvre et al 1997;Ulrich & Huguenard 1997), the threshold conductances predict that between 100 (control) and 660 (in vivo) GABAergic synapses must be co-activated to elicit a rebound burst in thalamic relay cells. Morphological studies indicate that a single axon from reticular neurons establish, on average, 60 synapses on the same postsynaptic relay cell (Kim et al 1997). Therefore, a relatively low convergence of between 2 and 10 reticular cells may securely evoke rebound bursts in thalamic relay neurons.…”

Anatomical and physiological considerations in thalamic rhythm generation

“…Each burst consists of somewhere between a few to tens of action potentials, and to the extent that each individual action potential is propagated throughout the neuron's axonal terminal arborization, the burst will evoke a compound synaptic response resulting from the summation of multiple unitary responses. Theoretical and experimental evidence suggests that the qualitative nature of the synaptic response can be influenced by presynaptic spike firing pattern (Destexhe and Sejnowski 1995;Kim et al 1997).…”

“…The relative contributions of the two types of receptors (GABA A and GABA B ) to the total IPSP seems to be somewhat dependent on the preparation, with prominent GABA B responses commonly observed under control or baseline conditions in rat somatosensory thalamic slices (Huguenard and Prince 1994b), less frequently observed in mouse (Warren et al 1994;Warren et al 1997), and rarely observed in ferret (Kim et al 1997). It remains to be determined what factors are responsible for these species and/or preparation differences, but it is clear that in each case GABA B dependent IPSPs can be produced with sufficient stimulation.…”