# Glutamate receptor signaling pathways in the circuit integration of adult-born neurons

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2021 · $439,734

## Abstract

Adult neurogenesis in the hippocampus occurs in the well-defined neurogenic niche in the subgranular zone of
the dentate gyrus. Newborn neurons are continuously generated and mature over the course of weeks to
integrate into the hippocampal circuit. Adult-born immature dentate gyrus cells (DGCs) have unique functional
properties that give them a privileged role in circuits that define specific behaviors, and which are critical to
episodic memory formation and retrieval. In particular these neurons play important roles in an animal’s ability
to separate similar patterns and disambiguate overlapping memories, processes that become impaired during
normal aging and in neurodegenerative and neuropsychiatric disorders. Therefore, mechanisms that regulate
adult-born DGC maturation and integration are important in understanding diverse neurological disorders
including Alzheimer’s disease, schizophrenia and post-traumatic stress disorders. Kainate receptors are a
class of glutamate receptor whose contributions to heterogeneous synaptic processes are still not fully
understood. The premise of these studies is built upon foundational studies in which we discovered that the
maturation of adult-born DGCs is more rapid after ablation of kainate receptors. We found that this effect was
likely through a disruption of intracellular Cl- gradient because of an effect on a neuronal Cl- transporter. We
will fully describe the altered molecular, synaptic, and functional alterations after loss of kainate receptor
signaling and will test whether GABA disruption is causal to the altered integration of maturating DGCs into the
hippocampal circuit. We will determine how altered maturation of adult-born DGCs affects the animal’s ability
to discriminate between similar patterns and temporal overlap of episodic memories and using in vivo
microendoscope imaging correlate cellular activity to behavioral measurements in a pattern separation task.
The goal of this project is to examine a new mechanism by which glutamate receptors affect adult-born DGC
integration by modulating GABA signaling. These studies would define novel processes that regulate adult-born neurons that could underlie the known involvement of kainate receptor signaling in mechanisms of
learning and memory.

## Key facts

- **NIH application ID:** 10219367
- **Project number:** 5R01NS115471-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Anis Contractor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $439,734
- **Award type:** 5
- **Project period:** 2020-08-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219367

## Citation

> US National Institutes of Health, RePORTER application 10219367, Glutamate receptor signaling pathways in the circuit integration of adult-born neurons (5R01NS115471-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219367. Licensed CC0.

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