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Title: Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures
Authors: McCafferty, Cian P.
David, Francois
Venzi, Marcello
Lorincz, Magor L.
Delicata, Francis
Atherton, Zoe
Recchia, Gregorio
Orban, Gergely
Lambert, Regis C.
Di Giovanni, Giuseppe
Leresche, Nathalie
Crunelli, Vincenzo
Keywords: Neural networks (Neurobiology)
Nervous system -- Diseases
Neural transmission -- Disorders
Neural transmission -- Regulation
Issue Date: 2018
Publisher: Nature Publishing Group
Citation: McCafferty, C., David, F., Venzi, M., Lőrincz, M. L., Delicata, F., Atherton, Z.,... Crunelli, V. (2018). Cortical drive and thalamic feed-forward inhibition control thalamic output synchrony during absence seizures. Nature Neuroscience, 1-13.
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.
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