# Role of Piriform Cortex Perineuronal Nets in Mouse Social Communication.

> **NIH NIH R15** · UNIVERSITY OF TENNESSEE KNOXVILLE · 2020 · $450,753

## Abstract

Rett Syndrome (RTT) is diagnosed as a neurodevelopmental disorder, characterized by partial or complete loss
of acquired spoken language, acquired motor skills and stereotypic hand movements. Mutations in X-linked gene
methyl CpG-binding protein 2 (MECP2), a chromatin remodeler and gene regulator, is the causative gene for
typical RTT. RTT is hypothesized to be the result of altered synaptic connectivity and plasticity caused by
abnormal experience-dependent synapse development and maintenance. However, few experimental paradigms
have explored how synaptic plasticity in RTT is affected over time and physiological changes with cellular, circuit
and behavioral level granularity.
Using Mecp2-null and heterozygous mouse models, we have previously shown that MECP2 regulates the timing
of experience-dependent plasticity in the adult auditory cortex in a learned maternal behavior paradigm. We
found that Mecp2-heterozygous females (SurHet) were inefficient gatherers, likely due to atypical auditory
perception, caused by an abnormal, transient increase in numbers of mature perineuronal nets (PNNs). PNNs
are extracellular matrix structures that act as physical barriers for plasticity, and form predominantly around
cortical parvalbumin GABAergic neurons.
Major questions remain: Pup retrieval behavior is a complex sequence of events involving auditory, tactile,
olfactory senses and goal-directed motor events. How do different sensory inputs (pup vocalizations, feel and
smell of pups) contribute to the motor outputs (adult vocalizations, goal-directed search and carrying pups by
mouth to the nest)? Our aims in this R15 proposal are to (1) characterize vocalizations/syllables and interactions
between pups and adult females during pup gathering task, using integrated analysis of audio and video
recordings with new machine learning algorithms; (2) identify the time line of altered PNN expression in
piriform cortex, a brain region thought to be important for olfactory coding and a relay station for multisensory
integration using immunostaining/imaging and then, surgical manipulations of piriform cortex. We hypothesize
that expression of mature PNNs in the piriform cortex is regulated by MECP2 and contribute to proper
integration and functioning of distinct components of pup retrieval behavior. The results from this study aims to
identify novel circuits and mechanisms involved in multisensory integration of vocal communication during
complex social behavior, which are one of the most striking yet underexplored phenotypes in RTT.
Relevance to health: Rett Syndrome is diagnosed as a neurodevelopmental disorder with sensory, motor and
social impairments; however, it is currently unknown where and how these impairments develop and change
over time in adulthood. This proposal aims to understand how plasticity, the ability of the brain to incorporate
and adapt to changes in its environment and surroundings, is affected by mutated genes in RTT and associated
neurological...

## Key facts

- **NIH application ID:** 10045956
- **Project number:** 1R15MH124042-01
- **Recipient organization:** UNIVERSITY OF TENNESSEE KNOXVILLE
- **Principal Investigator:** KEERTHI KRISHNAN
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $450,753
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10045956

## Citation

> US National Institutes of Health, RePORTER application 10045956, Role of Piriform Cortex Perineuronal Nets in Mouse Social Communication. (1R15MH124042-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10045956. Licensed CC0.

---

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