Action Potential Generation and Propagation in Neocortical Interneuron Axons Sophie Rose Liebergall

Format:

Book

Thesis/Dissertation

Author/Creator:

Liebergall, Sophie Rose, author.

Contributor:

University of Pennsylvania. Neuroscience., degree granting institution.

Language:

English

Subjects (All):

0306.

0317.

0719.

Local Subjects:

0306.

0317.

0719.

Physical Description:

1 electronic resource (200 pages)

Contained In:

Dissertations Abstracts International 87-07B

Place of Publication:

Ann Arbor : ProQuest Dissertations and Theses, 2025

Language Note:

English

Summary:

The axon is the site of action potential generation and propagation, and thus serves as an important locus of neuronal computation. However, the small diameter and complex morphology of axons in the mammalian central nervous system, particularly interneuron axons, has made direct assessment of axonal function and dysfunction technically challenging. As such, mammalian central axons are generally assumed to reliably propagate action potentials that are recorded at the soma to synaptic terminals. In this study, I performed direct electrophysiology recordings of axonal action potential propagation fidelity in neocortical interneurons during prolonged, high-frequency firing. I found that neocortical interneurons display use-dependent changes in axonal action potential propagation fidelity, which is present across species and may be relevant to the mechanism of the failure of inhibitory restraint during focal-onset seizures. Additionally, I assessed the cell-type-specific effects of haploinsufficiency of the axon-expressed sodium channel, Nav1.1. I found that in Scn1a+/- mice, Neuron-derived neurotrophic factor (Ndnf) expressing Layer 1 interneurons are the only neocortical interneuron subtype that does not rely on Nav1.1 and therefore does not show impaired excitability, as measured by intrinsic physiology, synaptic physiology, and in vivo Ca2+ imaging, in the context of Nav1.1 haploinsufficiency. The work presented in this thesis highlights that the axon is an important locus for the regulation of the action potential waveform in mammalian central neurons, in a cell-type-specific fashion. Furthermore, the axon, particularly the distal axon, may play an underappreciated role in the pathophysiology of neurologic diseases such as epilepsy

Notes:

Advisors: Goldberg, Ethan M. Committee members: Ma, Minghong; Machado, Timothy A.; Lorenzo, Damaris; Nusbaum, Michael P.

Source: Dissertations Abstracts International, Volume: 87-07, Section: B.

Ph.D. University of Pennsylvania 2025

Vendor supplied data

Local Notes:

School code: 0175

ISBN:

9798276007038

Access Restriction:

Restricted for use by site license