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Higher order thalamic nuclei facilitate the generalisation and maintenance of Spike and Wave Discharges in a genetic model of Absence Epilepsy

Atherton, Zoe 2021. Higher order thalamic nuclei facilitate the generalisation and maintenance of Spike and Wave Discharges in a genetic model of Absence Epilepsy. PhD Thesis, Cardiff University.
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Spike and wave discharges (SWD), generated by the cortico-thalamo-cortical (CTC) network, are pathological, large amplitude oscillations and the hallmark of absence seizures. SWD begin in an initiation network in both humans and animal models, including the genetics absence epilepsy rats from Strasbourg (GAERS), where it is in the primary somatosensory cortex (S1). The mechanisms of how SWD rapidly spread across the brain is unknown. This thesis investigates mechanisms beyond the principal CTC network, i.e. in higher-order thalamic (HO) nuclei to explore their role in the generalisation of SWD in freely moving GAERS. Their diffuse connectivity, altered synaptic anatomy in GAERS and known interactions with the initiation network, make these nuclei serious potential candidates. Firstly, HO nuclei and cortical local field potentials revealed a novel feature of cortical SWD: synchrony in cortical regions far from S1 (such as primary visual cortex, V1) become transiently unsynchronised with the SWD, i.e. there are short breaks in SWD (named SWD-breaks). Additionally, SWD can occur in S1 only or in S1 and the neighbouring primary motor cortex (M1), but not elsewhere. These spontaneous events provided a unique insight since they represent unsuccessful maintenance and generalisation of SWD. Afterwards, the relevance of CTC relationships was verified by local inhibition of HO nuclei with muscimol. This increased the delay of SWD propagation and occurrence of SWD-breaks. Finally, neural dynamics of HO nuclei single units revealed three groups of putative excitatory neurons. All groups exhibited a switch from tonic to burst firing before onset of SWD, but they responded differently during V1 SWD-breaks and unsuccessfully generalised SWD. The results of these experiments converge on two main conclusions: that trans-thalamic cortical communication is utilised in the initial propagation of SWD and also has an active role in maintaining cortical synchrony throughout the paroxysmal activity.

Item Type: Thesis (PhD)
Status: Unpublished
Schools: Biosciences
Subjects: Q Science > Q Science (General)
Date of First Compliant Deposit: 18 June 2021
Last Modified: 18 Jun 2022 01:30

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