Mechanisms Of Decreased Brainstem Arousal In Limbic Seizures: In Vivo Whole-Cell Recordings

Author

John Paul AndrewsFollow

Date of Award

January 2018

Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)

Department

Medicine

First Advisor

Hal Blumenfeld

Abstract

Seizures are commonly regarded as disorders of neuronal hyperactivity, but evidence shows that temporal lobe seizures also cause reduced activity in subcortical arousal nuclei, including cholinergic neurons in the pedunculopontine tegmental nucleus (PPT), a key node of the reticular activating system. The synaptic mechanisms underlying the reduced ictal activity of cholinergic neurons in the PPT are unknown. Whole-cell in vivo recordings were made from PPT neurons in head-fixed rats to distinguish active inhibition from withdrawal of excitatory input as the driver of reduced ictal neuronal firing. A subset of PPT neurons exhibited reduced firing and hyperpolarization during seizures and stained positive for choline acetyltransferase. These PPT cholinergic neurons also showed increased input resistance, reduced membrane potential variance and fewer EPSP-like events during seizures. These data weigh against active ictal inhibition and support withdrawal of excitatory input as the dominant mechanism of decreased activity of cholinergic neurons in the PPT.

Comments

This is an Open Access Thesis.

Recommended Citation

Andrews, John Paul, "Mechanisms Of Decreased Brainstem Arousal In Limbic Seizures: In Vivo Whole-Cell Recordings" (2018). Yale Medicine Thesis Digital Library. 3371.
https://elischolar.library.yale.edu/ymtdl/3371