# Lateralized change in cortical neural networks in shank3 mutant mice

> **NIH NIH R03** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $79,188

## Abstract

Project summary
Aberrant lateralization in brain structure and function is linked to the neurodevelopmental disorders such
as autism spectrum disorders (ASD). We have recently reported a lateralized decrease in the number of
parvalbumin expressing (PV+) basket cells (BCs) in L2/3 of the somatosensory cortex in the dominant
hemisphere of adult Shank3-/- mouse model of ASD. The dominant hemisphere was identified by a
reaching task to define each animal’s dominant forepaw. We further used a marker to recognize the
specific extracellular matrix enwrapping BCs and found that the number of BCs was not different between
the two hemispheres, but rather, some BCs did not express detectable levels of PV (PV- BCs). Remarkably,
we showed a mechanical hypersensitivity in the dominant paw correlated with the decrease in the
number of PV+ BCs in the corresponding cortex. However, almost nothing is known regarding the
developmental trajectory of the observed lateralization in BCs and the impact of a reduction in PV
expression on the properties of BCs or pyramidal neurons in local neural circuits. In the present proposal,
we will first characterize interhemispheric differences in BC – pyramidal cell network properties in L2/3 of
the somatosensory cortex in the Shank3-/- mouse by a combination of in vivo calcium (Ca2+) imaging during
whisker stimulation and in vitro patch clamp recording. We investigate differences in the activity and
electrophysiological properties of PV+ BCs and the atypical PV- BCs present in Shank3-/- mice. Next, we will
evaluate changes in the output of the somatosensory cortex by in vivo Ca2+ imaging of L2/3 pyramidal cells
in the barrel cortex during whisker stimulation in Shank3-/- mice. Furthermore, to determine the excitation
/ inhibition ratio directly, we will use patch clamp recording to study the synaptic inputs to L2/3 pyramidal
cells during electrical stimulation of L4. Finally, we will identify the developmental trajectory of
interhemispheric differences in the number of L2/3 PV+ and PV- BCs in the somatosensory cortex of the
Shank3-/- mouse using immunohistochemistry. Results of the immunohistochemistry, electrophysiology
and calcium imaging studies proposed here will significantly increase our knowledge about the role of
lateralized changes in the dominant hemisphere in the pathophysiology of ASD and could provide the
means for new therapeutic approaches.

## Key facts

- **NIH application ID:** 10450250
- **Project number:** 1R03MH127401-01A1
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Tara Deemyad
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $79,188
- **Award type:** 1
- **Project period:** 2022-04-01 → 2022-08-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10450250

## Citation

> US National Institutes of Health, RePORTER application 10450250, Lateralized change in cortical neural networks in shank3 mutant mice (1R03MH127401-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10450250. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*