title: A new mode of corticothalamic transmission revealed in the Gria4(-/-) model of absence epilepsy.
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.
authors.affiliation: Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, California, USA.
authors.forename: Jeanne T
authors.initials: JT
authors.lastname: Paz
authors.forename: Astra S
authors.initials: AS
authors.lastname: Bryant
authors.forename: Kathy
authors.initials: K
authors.lastname: Peng
authors.forename: Lief
authors.initials: L
authors.lastname: Fenno
authors.forename: Ofer
authors.initials: O
authors.lastname: Yizhar
authors.forename: Wayne N
authors.initials: WN
authors.lastname: Frankel
authors.forename: Karl
authors.initials: K
authors.lastname: Deisseroth
authors.forename: John R
authors.initials: JR
authors.lastname: Huguenard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002540:Cerebral Cortex / Q000503:physiopathology*; D000075402:Channelrhodopsins; D004195:Disease Models, Animal; D004558:Electric Stimulation; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000235:genetics / Q000473:pathology*; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009434:Neural Pathways / Q000503:physiopathology; D009474:Neurons / Q000502:physiology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D010852:Picrotoxin / Q000494:pharmacology; D018091:Receptors, AMPA / Q000172:deficiency*; D013788:Thalamus / Q000503:physiopathology*
chemical_list: D000075402:Channelrhodopsins; D018756:GABA Antagonists; D008164:Luminescent Proteins; D009943:Organophosphorus Compounds; D010852:Picrotoxin; D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; C107353:CGP 54626