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McCafferty, Cian Patrick
Languages: English
Types: Doctoral thesis
Subjects: RC0321

Classified by OpenAIRE into

mesheuropmc: nervous system
Absence seizures (ASs) are the predominant form of seizure featuring in the idiopathic generalised epilepsies, and are the only seizure type of childhood absence epilepsy. They are characterised by behavioural arrest, impairment of consciousness and an electrographic signature of spike-and-wave discharges (SWDs) and are associated with psychosocial and cognitive impairment of development. The seizures are known to arise in the thalamocortical network, but the firing dynamics of thalamic neurones during seizure is not known. In vivo and in vitro studies have yielded contradictory results, suggesting predominant silence and regular burst firing respectively, but no studies have previously recorded from intact, single thalamic neurones in a freely moving model of absence epilepsy.\ud In this thesis it has been shown that, in Genetic Absence Epilepsy Rats from Strasbourg, thalamocortical (TC) neurones are mostly either silent or fire single spikes irregularly but synchronously during AS. T-type calcium channel-mediated bursts in neurones of the reticular thalamic nucleus (nRT) were frequently observed during full seizure expression. These cells expressed varied firing patterns ranging from regular burst firing to predominant silence, with similarly varying degrees of synchrony. It is also suggested that the nRT burst firing observed may be required for seizure generation. T-type calcium channel-mediated burst firing of TC neurones is neither necessary for, nor commonly observed in, the full generation or propagation of absence seizures\ud These results suggest that TC neurones are predominantly silent during AS. This is compatible with the idea of a cortical seizure initiator and driver, as suggested by the cortical initiation site and cortical abnormalities observed in multiple experimental AS models. The observations herein also confirm that the temporal relationship between thalamic firing and SWDs previously observed in anaesthetised animals is maintained in the freely moving condition, but suggest that there is a greater incidence of asynchronous thalamic activity during AS (particularly of nRT neurones) than previously suggested.\ud The firing dynamics of thalamic neurones observed are a crucial step towards understanding TC network activity during AS, and provide a significant insight into the role of the thalamus in alterations of sensation, movement, and consciousness associated with these seizures.

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