# Development of corticostriatal networks in health and disease

> **NIH NIH F31** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $21,960

## Abstract

Project Summary/Abstract
 Autism Spectrum Disorders (ASDs) are associated with dysfunctional corticostriatal networks.
Molecular control over development of these connections remains to be defined. Rare microdeletions in the
gene encoding the transsynaptic adhesion protein cadherin-8 (Cdh8) are implicated in ASDs. Cdh8 is
expressed in prefrontal cortex and striatum during early postnatal corticostriatal synaptogenesis. We
hypothesize that deficits in Cdh8-dependent control of developing corticostriatal synaptic circuitry
contributes to autism-related behaviors. To test this, we generated conditional Cdh8 knockout (cKO) mice
where I will selectively delete Cdh8 from striatal and/or cortical neurons early in postnatal development. In Aim
1, the effects of Cdh8 ablation on neuronal connectivity and synaptic plasticity of pre-and post-synaptic
corticostriatal neuronal populations will be studied by combining axonal tracing, whole-cell recording
approaches and morphometric analyses. In Aim 2, young adult Cdh8 cKO and control mice will be tested on
behavioral tasks that model deficits in cognitive flexibility, social contact and perseverative/obsessive behaviors
observed in autism. We expect significant deficits in corticostriatal connectivity and synaptic function leading to
impairments in striatally-based behaviors. Together, this project will reveal new details about normal
corticostriatal development, as well as identify potential molecular mechanisms that could become targets for
therapeutic treatment in ASDs.

## Key facts

- **NIH application ID:** 9930156
- **Project number:** 5F31MH115541-03
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Roxana Mesias
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $21,960
- **Award type:** 5
- **Project period:** 2018-06-15 → 2020-12-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930156

## Citation

> US National Institutes of Health, RePORTER application 9930156, Development of corticostriatal networks in health and disease (5F31MH115541-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9930156. Licensed CC0.

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