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

Document Type

Article

Publication Date

2011

Keywords

Biophysics, Cerebral-Cortex, Disease-Models-Animal, Electric-Stimulation, Electroencephalography, Epilepsy-Absence, Excitatory-Postsynaptic-Potentials, GABA-Antagonists, Luminescent-Proteins, Mice-Inbred-C57BL, Mice-Knockout, Neural-Pathways, Neurons, Organophosphorus-Compounds, Patch-Clamp-Techniques, Picrotoxin, Receptors-AMPA, Rhodopsin, Thalamus

JAX Source

Nat Neurosci 2011 Sep; 14(9):1167-73.

First Page

1167

Last Page

1173

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.

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