# Investigating perineuronal nets and hippocampal plasticity in early life adversity-induced anxiety

> **NIH NIH R01** · PRINCETON UNIVERSITY · 2022 · $405,000

## Abstract

PROJECT SUMMARY
Early life adversity is associated with an increased incidence of anxiety disorders in adulthood. Understanding
the cellular processes that connect early life stress with excessive anxiety may provide clues for the
development of new therapies to treat anxiety disorders. Studies in humans and rodents have identified
subregions of the hippocampus as important for anxiety regulation. Neuronal oscillations in both theta and
gamma frequency ranges in the hippocampus have been linked to anxious behavior and these oscillations are
driven by coordinated activity among a specific class of inhibitory interneurons, the parvalbumin positive (PV+)
basket cells. Perineuronal nets (PNNs), extracellular matrix structures that modulate plasticity and have been
linked to psychopathology, surround many PV+ basket cells. In mice, early life adversity increases PNN
formation around PV+ cells in the ventral hippocampus, raising the possibility that this change leads to early
life adversity-induced enhancement of neuronal oscillations and anxiety. Adult neurogenesis in the ventral
hippocampus is also impacted by early adverse experience and adult-generated granule cells are known to
synapse with PV+ basket cells. The possibility that connections between adult-generated neurons and
inhibitory interneurons are altered by postnatal stress, potentially through alterations in PNNs, and thus
produce enhanced neuronal oscillations and anxiety remains unknown. This proposal is designed to address
the gaps in our understanding about how early life stress alters hippocampal PNNs, adult-generated granule
cell connections with inhibitory interneurons, neuronal oscillations and anxiety and to explore the connections
among these effects. The proposed experiments will use a mouse model of early life stress, manipulations of
PNNs in the hippocampus, retroviral labeling of new granule cells in the hippocampus, immunolabeling
combined with confocal microscopy and electron microscopy, transgenic and retroviral-mediated manipulation
of adult-generated neuron number, in vivo electrophysiology during behavior and anxiety test analyses in adult
male and female mice. The studies in this proposal are designed to achieve three significant and related, but
not interdependent, aims regarding the influence of early life stress on hippocampal plasticity in adulthood with
the long-term goal of understanding the cellular changes that lead to increased neuronal oscillations and
anxiety.

## Key facts

- **NIH application ID:** 10397136
- **Project number:** 5R01MH117459-05
- **Recipient organization:** PRINCETON UNIVERSITY
- **Principal Investigator:** Elizabeth Gould
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2018-08-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10397136

## Citation

> US National Institutes of Health, RePORTER application 10397136, Investigating perineuronal nets and hippocampal plasticity in early life adversity-induced anxiety (5R01MH117459-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10397136. Licensed CC0.

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