Inhibitory interconnections control burst pattern and emergent network synchrony in reticular thalamus.
Inhibitory connections between neurons of the thalamic reticular (RE) nucleus are thought to help prevent spike-wave discharge (SWD), characteristic of generalized absence epilepsy, in thalamic and thalamocortical circuits. Indeed, oscillations in thalamic slices resemble SWD when intra-RE inhibition is blocked and are suppressed when intra-RE inhibition is enhanced. To elucidate the cellular mechanisms underlying these network changes, we recorded from RE cells during oscillations in thalamic slices and either blocked intra-RE inhibition with picrotoxin or enhanced it with clonazepam. We found that intra-RE inhibition limits the number and synchrony, but not the duration, of RE cell bursts. We then performed simulations that demonstrate how inhibition can shift network activity into a desynchronized mode simply by vetoing occasional RE cell bursts. In contrast, when intra-RE inhibition is blocked, RE cells burst synchronously, enabling even short RE cell bursts to promote epileptogenesis in two ways: first, by activating GABA(B) receptors, and second, through the GABA(B) receptor-independent emergence of network synchrony.
Sohal
Vikaas S
VS
Department of Neurology and Neurological Sciences, Stanford University Medical Center, Stanford, California 94305-5122, USA.
Huguenard
John R
JR
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D002998:Clonazepam / Q000494:pharmacology; D003198:Computer Simulation; D004594:Electrophysiology; D004832:Epilepsy, Absence / Q000209:etiology / Q000503:physiopathology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D066298:In Vitro Techniques; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000502:physiology*; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D002998:Clonazepam; D018756:GABA Antagonists; D018757:GABA Modulators; D010852:Picrotoxin; D011963:Receptors, GABA-A