title: Synaptic release generates a tonic GABA(A) receptor-mediated conductance that modulates burst precision in thalamic relay neurons.
abstract: Tonic inhibition has emerged as a key regulator of neuronal excitability in the CNS. Thalamic relay neurons of the dorsal lateral geniculate nucleus (dLGN) exhibit a tonic GABA(A) receptor (GABA(A)R)-mediated conductance that is correlated with delta-subunit expression. Indeed, consistent with the absence of delta-subunit expression, no tonic conductance is found in the adjacent ventral LGN. We show that, in contrast to the situation in cerebellar granule cells, thalamic delta-subunit-containing GABA(A)Rs (delta-GABA(A)Rs) do not contribute to a spillover component of IPSCs in dLGN. However, tonic activation of thalamic delta-GABA(A)Rs is sensitive to the global level of inhibition, showing an absolute requirement on the synaptic release of GABA. Thus, the tonic conductance is abolished when transmitter release probability is reduced or action potential-evoked release is blocked. We further show that continuous activation of delta-GABA(A)Rs introduces variability into the timing of low-threshold rebound bursts. Hence, activation of delta-GABA(A)Rs could act to destabilize thalamocortical oscillations and therefore have an important impact on behavioral state.
authors.affiliation: Biophysics Section, Blackett Laboratory, Imperial College, London SW7 2AZ, United Kingdom.
authors.forename: Damian P
authors.initials: DP
authors.lastname: Bright
authors.forename: M Isabel
authors.initials: MI
authors.lastname: Aller
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Brickley
mesh_terms: D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004056:Differential Threshold; D004553:Electric Conductivity; D005829:Geniculate Bodies / Q000166:cytology / Q000502:physiology; D006706:Homeostasis / Q000502:physiology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D011930:Reaction Time; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism; D013788:Thalamus / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D002712:Chlorides; D020033:Protein Isoforms; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid