A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy

Nat Neurosci. 2011 Aug 21;14(9):1167-73. doi: 10.1038/nn.2896.

Abstract

Cortico-thalamo-cortical circuits mediate sensation and generate neural network oscillations associated with slow-wave sleep and various epilepsies. Cortical input to sensory thalamus is thought to mainly evoke feed-forward synaptic inhibition of thalamocortical (TC) cells via reticular thalamic nucleus (nRT) neurons, especially during oscillations. This relies on a stronger synaptic strength in the cortico-nRT pathway than in the cortico-TC pathway, allowing the feed-forward inhibition of TC cells to overcome direct cortico-TC excitation. We found a systemic and specific reduction in strength in GluA4-deficient (Gria4(-/-)) mice of one excitatory synapse of the rhythmogenic cortico-thalamo-cortical system, the cortico-nRT projection, and observed that the oscillations could still be initiated by cortical inputs via the cortico-TC-nRT-TC pathway. These results reveal a previously unknown mode of cortico-thalamo-cortical transmission, bypassing direct cortico-nRT excitation, and describe a mechanism for pathological oscillation generation. This mode could be active under other circumstances, representing a previously unknown channel of cortico-thalamo-cortical information processing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biophysics
  • Cerebral Cortex / physiopathology*
  • Channelrhodopsins
  • Disease Models, Animal
  • Electric Stimulation
  • Electroencephalography
  • Epilepsy, Absence / genetics
  • Epilepsy, Absence / pathology*
  • Excitatory Postsynaptic Potentials / genetics
  • GABA Antagonists / pharmacology
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Pathways / physiopathology
  • Neurons / physiology
  • Organophosphorus Compounds / pharmacology
  • Patch-Clamp Techniques / methods
  • Picrotoxin / pharmacology
  • Receptors, AMPA / deficiency*
  • Thalamus / physiopathology*

Substances

  • Channelrhodopsins
  • GABA Antagonists
  • Luminescent Proteins
  • Organophosphorus Compounds
  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 4
  • Picrotoxin
  • CGP 54626