Inhibitory interconnections control burst pattern and emergent network synchrony in reticular thalamus

J Neurosci. 2003 Oct 1;23(26):8978-88. doi: 10.1523/JNEUROSCI.23-26-08978.2003.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / physiology
  • Animals
  • Biological Clocks / drug effects
  • Biological Clocks / physiology
  • Clonazepam / pharmacology
  • Computer Simulation
  • Electrophysiology
  • Epilepsy, Absence / etiology
  • Epilepsy, Absence / physiopathology
  • Excitatory Postsynaptic Potentials / physiology
  • GABA Antagonists / pharmacology
  • GABA Modulators / pharmacology
  • In Vitro Techniques
  • Intralaminar Thalamic Nuclei / drug effects
  • Intralaminar Thalamic Nuclei / physiology*
  • Models, Neurological
  • Nerve Net / physiology*
  • Neural Inhibition / physiology*
  • Neurons / drug effects
  • Neurons / physiology*
  • Picrotoxin / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*

Substances

  • GABA Antagonists
  • GABA Modulators
  • Receptors, GABA-A
  • Picrotoxin
  • Clonazepam