Morphophysiological and Microcircuit Development of Hippocampal Neurons in Type I Lissencephaly

Ekins, Tyler

Full Metadata

Overview

Year:: 2021
Contributor:: Ekins, Tyler (creator); Moore, Christopher (Reader); Le Pichon, Claire (Reader); Petros, Timothy (Reader); McBain, Chris (Advisor); Castillo, Pablo (Reader); Brown University. Department of Neuroscience (sponsor)
Genre:: theses
Subject:: Neurosciences; Fast-spiking interneurons; Epilepsy; Neural transmission; Developmental neurophysiology; Lissencephaly
Extent:: 12, 150 p.

Files

Description

Abstract:: Although Type I lissencephaly is one of the most severe cortical malformation disorders and is highly comorbid with epilepsy, the cellular and circuit mechanisms driving the epileptiform activity remain unclear. This thesis aims to investigate the impact of LIS1 haploinsufficiency and resulting neuronal migration deficits on the morphophysiological development and microcircuit formation of hippocampal CA1 neurons and the origin of epileptiform activity, with an emphasis on PV-containing interneurons, with a combination of genetics, immunohistochemistry, morphophysiology, pharmacology, and single-cell transcriptomics. Chapter 2 investigates the impact of lamination on microcircuit formation in subtypes of hippocampal PCs. We find a microcircuit deficit involving CCK+ interneurons and ectopic CB+PCs and find that in vitro gamma oscillations are less responsive to pharmacological inhibition of CCK+ interneurons in the LIS1 mutant. Chapter 3 focuses specifically on PV+ interneurons using global and cell type-specific LIS1 mutations. Disruptions to LIS1-dependent intrinsic developmental programs within interneurons, rather than ectopic positioning or pyramidal cell disorganization, results in the emergence of non-canonical PV+ interneurons. Compared to standard fast-spiking cells, these non-canonical PV+ interneurons have physiological properties that render them less able to balance excitation in hippocampal networks, likely contributing to epileptic seizures.
Notes:: Thesis (Ph. D.)--Brown University, 2021

Content

Citation

Ekins, Tyler, "Morphophysiological and Microcircuit Development of Hippocampal Neurons in Type I Lissencephaly" (2021). Neuroscience Theses and Dissertations. Brown Digital Repository. Brown University Library. https://repository.library.brown.edu/studio/item/bdr:fyrcjmq5/

Relations

Collection:

Neuroscience Theses and Dissertations

Theses and Dissertations for the Neuroscience department.
...