# Proteomic analysis of maturing adult-born hippocampal mossy fiber boutons

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2020 · $235,500

## Abstract

The birth of new neurons (called neurogenesis) in the adult hippocampus is critical for learning and memory and
disruption of this process is associated with human neurological disorders such as Alzheimer’s disease. Rates
of adult hippocampal neurogenesis (AHN) are tightly linked with changes in physiological activity. Activities such
as enhanced exercise or learning as well as pathophysiological changes such as epilepsy, profoundly alter AHN.
Knowing how ANH neurogenesis regulates neuronal circuitry is therefore important for understanding its overall
impact on brain physiology. Central to this issue is understanding how newborn neurons in adult brain achieve
long-term integration. Understand the molecular and cellular mechanisms regulating synaptic integration in AHN
could lead to selective pharmacological targets for functional improvement during pathological conditions or in
aging where levels of adult neurogenesis are dramatically decreased. Neuronal progenitors in the adult
hippocampal dentate gyrus give rise to newborn granule (GCs) cells that, when fully differentiated, receive
synaptic inputs from entorhinal cortex and send axons along the mossy fiber pathway to form synaptic outputs
with CA3 pyramidal neurons. We and others have shown that it takes about eight weeks for the newborn GCs
to fully differentiate and form mature synaptic inputs and outputs. The major focus of this proposal is to determine
the molecular changes in the synaptic outputs when newborn mossy fiber boutons from GC are forming synapses
with mature CA3 pyramidal cells. We propose to use superresolution immunofluorescent array tomography and
conjugate array tomography coupled with electron microscopy to profile the proteomic changes of the pre- and
post-synaptic elements during the establishment of mature synapses. We have found that to establish a mature
synaptic contact the mossy fiber can either 1) form a de novo nascent synapse or 2) replace an existing mossy
fiber bouton assuming control of the existing postsynaptic CA3 dendrite. The molecular mechanisms regulating
these disparate cellular processes are unknown. Here we will use array tomography analysis to profile the
proteomic changes in these synapses to test the hypothesis that the synaptic molecular composition of
integrating newborn neurons in adult hippocampus is highly dynamic during the entire maturation process. We
have two main focuses: (1) to establish a proteomic profile of the developing and mature presynaptic mossy fiber
terminal during adult hippocampal neurogenesis and (2) to establish a proteomic profile of the developing and
mature postsynaptic mossy fiber terminal during adult hippocampal neurogenesis. These experiments will be
the first to address the intricate proteomic changes essential for establishing new synaptic outputs during adult
neurogenesis and will potentially identify a pharmacological target for therapeutic strategies to improve the
function of adult brain.

## Key facts

- **NIH application ID:** 10018121
- **Project number:** 5R21NS115092-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** KARL Daniel MURRAY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $235,500
- **Award type:** 5
- **Project period:** 2019-09-15 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10018121

## Citation

> US National Institutes of Health, RePORTER application 10018121, Proteomic analysis of maturing adult-born hippocampal mossy fiber boutons (5R21NS115092-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10018121. Licensed CC0.

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