Mechanisms of high frequency activity in epileptic foci

Morris, Gareth Liam (2015). Mechanisms of high frequency activity in epileptic foci. University of Birmingham. Ph.D.

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Abstract

High frequency activity (HFA) is oscillatory brain activity faster than ~100 Hz. It is subdivided into physiological ripples (~100-250 Hz) and pathological fast ripples (~250-500 Hz). Ripples in the hippocampus are paced by recurrent inhibition from interneurons. The mechanism for pathological HFA is unknown, but may be the same as for ripples and could provide new insight into the pathological nature of epileptic tissue.
HFA was induced using the high potassium (\({in vitro}\)) and tetanus neurotoxin (\({ex vivo}\)) models of epilepsy. Field HFA was recorded simultaneously with action potentials from visually targeted interneurons, made possible using VGAT-Venus A rats and a membrane chamber. The phase relationship between HFA and interneuron firing was examined.
In both models, HFA frequency was normally distributed between 100-300 Hz. Interneurons increased their firing rate during epileptiform bursts and were subdivided into four groups based on their firing patterns. The most pertinent group fired at >100 Hz throughout epileptiform bursts and were candidates to pace HFA. Of this group, significant phase relationships were seen in four interneurons using high potassium and one interneuron with tetanus neurotoxin.
These interneurons were compatible with the hypothesis that they pace HFA, but blockade of GABAergic signalling using bicuculline did not abolish HFA, suggesting a modulatory rather than causative role for interneurons.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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