Abstracts

Mice With Hyperactive mTOR Signaling Show Communication Deficits During The Neonatal Period

Abstract number : 3.056
Submission category : 1. Basic Mechanisms / 1E. Models
Year : 2025
Submission ID : 165
Source : www.aesnet.org
Presentation date : 12/8/2025 12:00:00 AM
Published date :

Authors :
Presenting Author: Chloe Lau, BS – Baylor University

Sydney Pell, BS – Baylor University
Taylor Bradish, M.S. – Baylor University
Maria Hemmersmeier, BS – Baylor University
Colton Kelley, BS – University of California Davis
Joaquin Lugo, BS – Baylor University
Joaquin Lugo, PhD – Baylor University

Rationale:

Epilepsy is marked by a predisposition to experience recurrent seizures, which may arise from a variety of genetic and non-genetic causes. The mechanistic target of rapamycin (mTOR) pathway is a master regulator of cell growth, death, metabolism, and migration. Dysregulation of this pathway has been linked to both neurodevelopmental disorders, like autism spectrum disorder (ASD), and epilepsy. The deletion or mutation of phosphate and tensin homolog (PTEN) gene on chromosome ten—a suppressor of the mTOR pathway—has been associated with the development of epilepsy. Seizures in early development have been linked to autistic-like behavioral deficits, such as communication deficits.



Methods:

We used a neuronal subset-specific PTEN (NS-PTEN) mouse model to investigate the communication differences among wildtype (WT), heterozygous (HT), and knockout (KO) genotypes in both male and female mice. The NS-PTEN KO mouse is a well-characterized mouse model of epilepsy. Ultrasonic vocalizations (USVs) were used to examine communication alterations in mice. Mouse pups commonly vocalize during their first 2 weeks of life and emit sounds to elicit a retrieval response from the dam. We chose to examine postnatal days (PD) 14, as this represents a time with a high vulnerability to seizures and marks the end of a critical period of development. We evaluated differences in genotype on call types and aspects of total calls.



Results:

An analysis of the distribution of call types found that female KO had more chevron and frequency step calls and less complex and upward calls than female WT and HT mice (p < .05). Male KO were found to have more chevron, frequency step and two-component calls, and less complex, short and upward calls that WT and HT males (p < .05). Additionally, we found that females had a greater percent of multiple calls compared to male mice at PD14 (p < .05). Moreover, we did not find any significant genotype and sex interaction differences in USV spectral properties (i.e., latency, power, total call duration).

Basic Mechanisms