# Synaptic Mechanisms for Contextual Memory Formation

> **NIH NIH R01** · UPSTATE MEDICAL UNIVERSITY · 2022 · $671,992

## Abstract

Learning and memory defines how animals interact with their environment. This process relies on
experience-driven changes in synaptic connections, a phenomenon known as synaptic plasticity;
disruption of this process is believed to underlie several cognitive and psychiatric disorders.
Although synaptic plasticity is critical for learning and memory, the mechanisms by which memory
is formed and stored in neural circuits remains poorly understood. The proposed studies address
this knowledge gap by focusing on synaptic mechanisms by which contextual memory is encoded
in CA3 pyramidal neurons of the hippocampus, a brain region with a central role in learning and
memory. Among the excitatory inputs converging onto CA3 pyramidal neurons, the mossy fiber
(MF) input from dentate gyrus granule cells is known to be required for the encoding of contextual
memory. Using genetic tools recently developed by us, we were able to identify the specific group
of CA3 neurons activated by contextual learning, and identified a learning-dependent synaptic
modifications associated with these neurons. We hypothesize that this newly identified synaptic
plasticity plays a critical role in contextual memory formation. This hypothesis will be tested using
a combination of molecular, cellular, electrophysiological and behavioral approaches in mice. We
will also identify molecular pathways that selectively modulate MF-CA3 synapses in the mouse
hippocampus. The proposed research has the potential to generate conceptual breakthroughs in
our molecular and cellular understanding of memory formation, and ultimately provide insights
into mechanisms underlying cognitive and psychiatric impairments.

## Key facts

- **NIH application ID:** 10294231
- **Project number:** 5R01MH116673-05
- **Recipient organization:** UPSTATE MEDICAL UNIVERSITY
- **Principal Investigator:** PABLO E CASTILLO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $671,992
- **Award type:** 5
- **Project period:** 2018-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10294231

## Citation

> US National Institutes of Health, RePORTER application 10294231, Synaptic Mechanisms for Contextual Memory Formation (5R01MH116673-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10294231. Licensed CC0.

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