Type

Text

Type

Dissertation

Advisor

Ge, Shaoyu | Parsey, Ramin | Enikolopov, Grigori | Role, Lorna | Hen, René

Date

2017-12-01

Keywords

Neurosciences | adult neurogenesis | Pharmacology | enriched environment | hippocampus | neural stem cells

Department

Department of Molecular and Cellular Pharmacology

Language

en_US

Source

This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.

Identifier

http://hdl.handle.net/11401/78278

Publisher

The Graduate School, Stony Brook University: Stony Brook, NY.

Format

application/pdf

Abstract

Adult brains are constantly reshaping themselves from synapses to circuits as we encounter novel experiences from moment to moment. Importantly, this reshaping also includes the addition of newborn hippocampal neurons. However, it remains largely unknown how our circuits encode experience-induced brain activity to govern the addition of new hippocampal neurons. By coupling in vivo Ca2+ imaging of dentate granule neurons with a novel, unrestrained virtual reality system for rodents, we discovered that a new experience rapidly and robustly increased the firing of active dentate granule neurons, and was accompanied by an accumulative enhancement in the addition of new hippocampal neurons. Silencing this activation optogenetically during novel experiences perturbed experience-induced neuronal addition. Given the high metabolic demands associated with maintaining a continuous pool of proliferating and maturing cells, we next asked whether the addition of new hippocampal neurons is regulated by the vascular supply. We developed a technique to non-invasively target astrocytes, cells that couple neuronal activity to vascular recruitment. Upon genetic ablation of astrocytes, we observed sharply decreased survival of newborn hippocampal neurons. Together, these data provide new insights into how experience and brain activity shape the ongoing generation of new neurons in the adult brain. | 169 pages

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