Corticothalamic and thalamocortical components of absence seizure ictogenesis

01/29/2020

François David¹

¹ Integrative Neuroscience and Cognition Center, University Paris-Descartes, France

The thalamus and cortex form reciprocally connected networks responsible for sensory processing and generate brain rhythms that are tightly linked to brain functions such as sleep, memory consolidation or perception. The same networks also generate pathological spike-and-wave discharges (at 2.5-4 Hz) during absence seizures. These paroxysmal oscillations rely on intrinsic mechanisms and inter-area synaptic processes, which result in 1) the dysfunction of inhibitory circuits at the thalamic and cortical levels and 2) a runaway excitation that propagates across the entire brain. Paradoxically, thalamus and cortex were recently shown to be partially inhibited during those events. Our experimental animal recordings of thalamic and cortical neuron assemblies showed for the first time the presence of bidirectional functional and dysfunctional neuronal connections between thalamus and cortex that could account for this excitatory/inhibitory net effect in cortical and thalamic networks. Moreover, intrinsic cellular properties mediated by low-threshold calcium channels i.e. high-frequency bursts, in the thalamic network were pharmacologically and electrophysiologically identified to play a critical role at the thalamic reticular and the cortical levels while playing no role at the sensory thalamic nuclei level. These results reveal some principles of thalamocortical and corticothalamic communications and pave the way for a new understanding of absence seizures which are still not fully controlled by current medications.