Author Type

Graduate Student

Date of Award

2018

Document Type

Dissertation

Publication Status

Version of Record

Submission Date

October 2026

Thesis/Dissertation Advisor [Chair]

Guthrie, Kathleen

Abstract

Olfactory Granule cells (GCs) are a population of inhibitory interneurons responsible for maintaining normal olfactory bulb (OB) function and circuitry. Through dendrodendritic synapses with the OBs projection neurons, the GCs regulate information sent to the olfactory cortices. Throughout adulthood, GCs continue to integrate into the OB and contribute to olfactory circuitry. However, only ~50% will integrate and survive longterm. Factors aiding in the survival and morphological development of these neurons are still being explored. The neurotrophin brain-derived neurotrophic factor (BDNF) aids in the survival and dendritic spine maturation/maintenance in several populations of CNS neurons. Investigators show that increasing BDNF in the adult-rodent SVZ stimulates proliferation and increases numbers of new OB GCs. However, attempts to replicate these experiments failed to find that BDNF affects proliferation or survival of adult-born granule cells (abGCs). BDNFs regulation of dendritic spines in the CNS is well characterized. In the OB, absence of BDNF’s receptor on abGCs hinders normal spine development and demonstrates a role for BDNF /TrkB signaling in abGCs development. In this study, we use transgenic mice over-expressing endogenous BDNF in the OB (TgBDNF) to determine how sustained increased in BDNF affect the morphology of olfactory GCs and the survival and development of abGCs. Using protein assays, we discovered that TgBDNF mice have higher BDNF protein levels in their OB. We employed a Golgi-cox staining technique to show that increased BDNF expression leads to an increase in dendritic spines, mainly the mature, headed-type spine on OB GCs. With cell birth-dating using 5-bromo-2’- deoxyuridine (BrdU), immunofluorescent cell markers, TUNEL staining and confocal microscopy, we demonstrate that over-expression of BDNF in the OB does not increase survival of abGCs or reduce cell death in the GC population. Using virally labeled abGCs, we concluded that abGCs in TgBDNF mice had similar integration patterns compared to wild-type (WT) mice, but maintained increases in apical headed-type spine density from 12 to 60 days PI. The evidence combined demonstrates that although increased BDNF does not promote cell survival, BDNF modifies GC morphology and abGC development through its regulation of dendritic spine development, maturation and maintenance in vivo.

Extent

163 p.

Comments

Includes bibliography.|Dissertation (Ph.D.)--Florida Atlantic University, 2018.|FAU Electronic Theses and Dissertations Collection|Includes bibliography.

Identifier

FA00013159

Format

pdf

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