# Synaptic integration, calcium dynamics, and plasticity in striatum spiny projection neurons

> **NIH NIH F31** · GEORGE MASON UNIVERSITY · 2020 · $24,736

## Abstract

Plasticity in the striatum supports habit and goal-directed learning, and aberrant plasticity contributes to
addiction and substance abuse. The principle cells of the striatum—spiny projection neurons (SPNs)—
integrate cortical, thalamic, dopaminergic, and local inhibitory inputs. Dorsomedial striatum (DMS) receives
input from associative cortex to mediate goal-directed learning, and dorsolateral striatum (DLS) receives input
from sensorimotor cortex to mediate habit learning. Plasticity in both regions requires intracellular calcium
elevation. The magnitude, duration, and location of calcium influx is hypothesized to determine the outcome of
synaptic plasticity, consistent with in vitro brain slice experiments. Most striatal plasticity findings are from in
vitro experiments conducted with regular, repeated inputs. It is unclear how in vivo-like inputs affect calcium
dynamics and synaptic plasticity, limiting the applicability of ex vivo plasticity findings to in vivo conditions.
Therefore, the overarching goal here is to integrate ex vivo mechanisms with in vivo-like conditions to
determine plasticity outcomes in response to cortical activity. Further, this project will determine contributions
of intrinsic cellular mechanisms and network activity to observed differences in DMS and DLS plasticity. To
translate in vitro plasticity findings to in vivo like conditions, experimentally-constrained computational models
of SPNs will be developed and morphological reconstruction experiments conducted to investigate effects of
synaptic activity patterns on plasticity. Simulation experiments will evaluate the central hypothesis that in
vivo-like patterns of synaptic input will support striatal synaptic plasticity by addressing the following
aims. Aim 1: Test the hypothesis that spatiotemporal patterns of synaptic input will produce nonlinear
spatially specific spine calcium. Multiple synaptic inputs placed with spatially clustered or distributed
patterns and activated with temporal variability will be simulated and their effects on spine calcium dynamics
evaluated to delineate rules governing control of calcium dynamics. Aim 2: Test the hypothesis that in vivo-
like patterns of synaptic input will produce consistent calcium elevations and synaptic plasticity in a
subset of spines. In vivo-like input patterns will be constructed from cortical spike trains and simulated with
various degrees of trial-to-trial variability to identify the sensitivity of plasticity to variable cortical inputs during
repeated trials. Aim 3: Determine whether differences in dorsomedial and dorsolateral plasticity depend
on intrinsic cellular differences or differences in presynaptic activity. Cell-type specific models of
dorsomedial and dorsolateral SPNs will be developed from morphological reconstruction of neurons to
determine whether differences in plasticity underlying goal-directed versus habit learning depend on intrinsic
cellular properties, morphology, and/or synaptic inpu...

## Key facts

- **NIH application ID:** 9996317
- **Project number:** 5F31DA047145-02
- **Recipient organization:** GEORGE MASON UNIVERSITY
- **Principal Investigator:** Daniel B Dorman
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $24,736
- **Award type:** 5
- **Project period:** 2019-08-25 → 2021-04-11

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996317

## Citation

> US National Institutes of Health, RePORTER application 9996317, Synaptic integration, calcium dynamics, and plasticity in striatum spiny projection neurons (5F31DA047145-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9996317. Licensed CC0.

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