# Neural Circuit Activity Dynamics Supporting Temporal Association Fear Memory

> **NIH NIH K08** · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · 2021 · $58,951

## Abstract

Dysregulation of learning and memory processes is often a core and disabling clinical component of a broad
variety of neuropsychiatric disorders. For example, the healthy brain continuously links discontiguous,
sequential experiences across time. However, in patients who have developed PTSD, a neutral cue may trigger
severe symptoms if previous exposure to a similar cue had been temporally followed by, and became
mnemonically associated with, a traumatic event. Such temporal association memories can be studied with
`trace' fear conditioning paradigms that require selective hippocampal (HPC) circuitry and may also engage
distributed prefrontal-thalamo-hippocampal circuits. However, the neural circuit activity mechanisms
underlying the key processes of mnemonic temporal association and fear regulation remain largely unclear.
This project studies circuit activity mechanisms for these systems level mental processes using current state-of-
the-art techniques for combined neural circuit activity monitoring and perturbation. Thus, 2-photon activity
imaging of circuit dynamics, opto- and pharmacogenetic manipulations, multi-site electrophysiological
recordings of neural activity, and computational analyses, will all be applied to study learning and memory
processes in awake, behaving mice. First, the dynamic HPC output activity mechanisms associated with `trace'
fear memory will be identified using 2-photon imaging of cellular network activity during learning (Aim 1).
Next, the role of long-range and local microcircuit inputs in potentially regulating `trace' fear memories
through this HPC circuit output (Aim 2) will be tested using a combination of presynaptic activity imaging,
circuit perturbation, and imaging of postsynaptic output activity. Finally, the hypothesis that coordination
between prefrontal-thalamo-hippocampal systems is important for `trace' fear memories will be tested (Aim 3)
using simultaneous recordings of neural activity from distant brain regions and optogenetic inhibition of
circuit elements. The project builds directly from the PI's prior studies in synaptic physiology, plasticity, and
microcircuit dynamics underlying learning and memory in the HPC and leverages previous experience with
some of the techniques applied here. The award proposes a program for expanded training with established
basic and translational science experts in circuit, systems, computational, and behavioral neurosciences, to
facilitate the PI's development into an independent physician-scientist investigator focusing on memory
dysregulation in neuropsychiatric disorders.

## Key facts

- **NIH application ID:** 10357376
- **Project number:** 3K08MH113036-04S1
- **Recipient organization:** NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
- **Principal Investigator:** Mohsin Saeed Ahmed
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $58,951
- **Award type:** 3
- **Project period:** 2021-02-20 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10357376

## Citation

> US National Institutes of Health, RePORTER application 10357376, Neural Circuit Activity Dynamics Supporting Temporal Association Fear Memory (3K08MH113036-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10357376. Licensed CC0.

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