# Newborn Neurons in the Adult Hippocampal Network

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $502,859

## Abstract

The dentate gyrus contributes to hippocampal memory encoding by transforming dense cortical
patterns of sensory and spatial information into sparse neural representations of specific contexts. There is
now overwhelming evidence that continual adult neurogenesis in the dentate gyrus in important for the ability
to discriminate spatial contexts, but it is not clear how newly generated neurons contribute to dentate circuit
function. Most theories have focused on the fact that newly-generated immature neurons have distinct
physiological properties that potentially endow them with unique processing capabilities compared to larger
population of mature neurons. Alternatively, an emerging idea is that adult-born neurons promote wide-spread
plasticity of the pre-existing cortical-dentate circuit by modifying the function of existing neurons in a manner
that promotes sparse activity. This could occur either by indirect circuit actions like feedback inhibition, as well
as via direct interactions with existing excitatory synaptic connectivity. We recently showed that selectively
increasing the number of adult-born neurons in mouse dentate gyrus reduces the excitatory synaptic
connectivity of mature neurons, resulting in both functional and anatomical changes in entorhinal-dentate
circuitry. These results and existing literature support a model wherein a static pool of cortical pre-synaptic
terminals is dynamically distributed between newly integrating adult-born neurons and developmentally-
generated mature neurons. The goal of this project is to test the overarching hypothesis that synaptic
integration of adult-born neurons has disproportionate effects on circuit function via redistribution of
cortical synaptic connectivity. First, we will map and quantify the presynaptic changes that accompany
neurogenesis-induced loss of cortical synapses with mature neurons. Second, we will test the prediction that
availability of cortical presynaptic terminals is a limiting factor in the integration of newborn GCs that potentially
contributes to the reduced rate new neuron maturation across adulthood. Finally, we will test potential
consequences of synaptic redistribution on the sparsity of neural activity and synaptic plasticity, and the
requirement for synaptic redistribution for neurogenesis-sensitive behaviors. We will use a combination of viral
manipulations, electrophysiology, imaging and behavioral analysis to test the prediction that synaptic re-
distribution limits the integration of adult-born neurons during adulthood and sparsifies neural activity, as well
as contributes to behaviors that are sensitive to neurogenesis. Together our results will generate fundamental
new knowledge about the role of neurogenesis in cortical-dentate circuitry, and potentially provide insight into
how this circuit changes across adulthood as neurogenesis declines. Understanding how neurogenesis
contributes to hippocampal function is important for devising strategies to counteract ...

## Key facts

- **NIH application ID:** 9883845
- **Project number:** 5R01NS064025-11
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Linda Overstreet-Wadiche
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $502,859
- **Award type:** 5
- **Project period:** 2009-02-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883845

## Citation

> US National Institutes of Health, RePORTER application 9883845, Newborn Neurons in the Adult Hippocampal Network (5R01NS064025-11). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9883845. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
