# Synaptic mechanisms of temporal pattern separation

> **NIH NIH RF1** · YALE UNIVERSITY · 2020 · $1,090,650

## Abstract

PROJECT SUMMARY
 Pattern separation is the process by which the brain distinguishes between similar or overlapping
features of the external world. This fundamental computation is performed by multilayered circuits – including
the dentate gyrus, cerebellar cortex, and insect mushroom body – that expand and diversify neural
representations. Diversity in “space” (i.e. the identities of neurons responding to a given stimulus) is achieved
by sparse and unstructured synaptic connectivity, but we currently lack an understanding of how synapses
generate diversity in time to support temporal pattern separation. This gap is due to two basic challenges: (1)
measuring dynamical properties of multiple synaptic inputs to a given neuron and (2) causally perturbing those
properties while monitoring downstream neurons and behavior.
 Here we propose to overcome these challenges, by investigating synaptic mechanisms of temporal
pattern separation in a tractable experimental system: the mushroom body of the fruit fly, Drosophila. We have
developed new methods to rapidly characterize the short-term plasticity dynamics of multiple synaptic inputs to
a single neuron, as well as genetic strategies to perturb these dynamics. This enables a systematic
examination of how synapses generate diversity over time to separate fine temporal differences in sensory
inputs. In Aim 1, we will determine how populations of mushroom body neurons use temporal diversity to
expand their sensory coding capacity. In Aim 2, we will combine 2-photon optogenetic stimulation with whole-
cell electrophysiology to examine the organization of short-term plasticity properties across the synaptic inputs
to the mushroom body. In Aim 3, we will experimentally manipulate short-term plasticity at mushroom body
input synapses to study their role in associative learning. Together, these studies will reveal synaptic and
cellular mechanisms for temporal pattern separation in the mushroom body.
 Although there are differences between flies and mammals, the basic logic of pattern separation is
strikingly conserved between circuits of invertebrates and vertebrates. These similarities suggest that
discoveries made in the fruit fly will be relevant to the mechanisms of temporal pattern separation in other
animals. A more thorough understanding of how short-term synaptic plasticity implements higher-order
computations has the potential to transform our understanding of the role of timing in learning and memory,
which could lead to improved treatments for memory-related disorders.

## Key facts

- **NIH application ID:** 9970802
- **Project number:** 1RF1NS116584-01
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** James McClure Jeanne
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,090,650
- **Award type:** 1
- **Project period:** 2020-05-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9970802

## Citation

> US National Institutes of Health, RePORTER application 9970802, Synaptic mechanisms of temporal pattern separation (1RF1NS116584-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9970802. Licensed CC0.

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