All ETDs from UAB

Advisory Committee Chair

Linda Wadiche

Advisory Committee Members

Jacques I Wadiche

Lori L McMahon

David Sweatt

Candace L Floyd

Document Type

Dissertation

Date of Award

2015

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

The hippocampus encodes sensory information into memories. The dentate gyrus (DG) region is viewed as the entry point into the hippocampus, receiving sensory and spatial signals from perforant path axons of the entorhinal cortex (EC). Ever since researchers discovered a neurogenic niche in the subgranular zone (SGZ) of the DG in adult animals and humans, many studies have been aimed at discovering how these continually proliferating granule cells (GCs) contribute to the network. Immature GCs have dendrites that project densely into the molecular layer alongside mature GCs and there is morphological evidence that immature excitatory spines preferentially synapse onto existing boutons. Therefore, it is likely that the addition of new GCs alters preexisting connections. Here we give an introduction to the possible functions of the DG and its relevance to human memory, then briefly review what is known about cell death, plasticity and synapse competition in the DG as well as other CNS regions. We then present a body of work that shows evidence for functional synaptic competition between immature and mature GCs. We also show that eliminating the pro-apoptotic Bax gene in mature GCs prevents competition-induced rewiring of the circuit. Finally, we discuss the implications of this work and present further evidence that manipulating neurogenesis affects the DG network.

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