Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures

McCafferty, Cian, David, Francois, Venzi, Marcello, Lorincz, Magor L., Delicata, Francis, Atherton, Zoe, Recchia, Gregorio, Orban, Gergely, Lambert, Regis C., Di Giovanni, Giuseppe, Leresche, Nathalie and Crunelli, Vincenzo ORCID: https://orcid.org/0000-0001-7154-9752 2018. Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures. Nature Neuroscience 21 , pp. 744-756. 10.1038/s41593-018-0130-4

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Abstract

Behaviorally and pathologically relevant cortico-thalamo-cortical oscillations are driven by diverse interacting cell-intrinsic and synaptic processes. However, the mechanism that gives rise to the paroxysmal oscillations of absence seizures (ASs) remains unknown. Here we report that, during ASs in behaving animals, cortico-thalamic excitation drives thalamic firing by preferentially eliciting tonic rather than T-type Ca2+ channel (T-channel)-dependent burst firing in thalamocortical (TC) neurons and by temporally framing thalamic output via feedforward reticular thalamic (NRT)-to-TC neuron inhibition. In TC neurons, overall ictal firing was markedly reduced and bursts rarely occurred. Moreover, blockade of T-channels in cortical and NRT neurons suppressed ASs, but such blockade in TC neurons had no effect on seizures or on ictal thalamic output synchrony. These results demonstrate ictal bidirectional cortico-thalamic communications and provide the first mechanistic understanding of cortico-thalamo-cortical network firing dynamics during ASs in behaving animals.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Nature Publishing Group
ISSN:	1097-6256
Date of First Compliant Deposit:	13 March 2018
Date of Acceptance:	8 March 2018
Last Modified:	06 Nov 2024 03:00
URI:	https://orca.cardiff.ac.uk/id/eprint/109829

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