Advisory Committee Chair
Linda Overstreet-Wadiche
Advisory Committee Members
Rita M Cowell
Lynn Dobrunz
Craig Powell
Jacques I Wadiche
Document Type
Dissertation
Date of Award
2023
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Neurogenesis occurs in the dentate gyrus of adult rodents leading to a heterogeneous population of dentate granule cells (GCs) in the granule cell layer. Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that contributes to their role in dentate gyrus function. Various mechanisms have been proposed to underlie the critical period of plasticity, including minimal GABAergic synaptic inhibition, robust NMDAR2B currents, and high intrinsic excitability conferred by T-type Ca2+ channels. In this collection of work, we investigate the critical period for long-term potentiation (LTP) in 4–6-week-old abGCs. We conclude that GABAergic inhibition regulates LTP in 4-week-old abGCs, as previous studies suggest, and we show that NMDAR-mediated depolarization is similar to mature GCs during TBS induction of LTP. We further discovered that blockade of T-type Ca2+ channels in young abGCs suppresses LTP when inhibition is intact, and that blocking T-type Ca2+ channels during TBS eliminates NMDAR-mediated depolarization. We discuss the expression of T-type Ca2+ channels across GC maturation and propose a mechanism explaining T-type Ca2+ channel contribution to the LTP critical period. Together these results show that T-type Ca2+ channels underlie a critical period of plasticity in young abGCs and allow 4-6-week-old abGCs to overcome synaptic inhibition.
Recommended Citation
Kennedy, William Michael, "The Critical Period Of Long-Term Plasticity In Adult-Born Granule Cells Is Mediated By T-Type Calcium Channels" (2023). All ETDs from UAB. 3506.
https://digitalcommons.library.uab.edu/etd-collection/3506