Sex Differences In Ultrasonic Vocalization in Rat Pups

3276 • The Journal of Neuroscience, February 20, 2013 • 33(8):3276 –3283

Behavioral/Cognitive

Foxp2 Mediates Sex Differences in Ultrasonic Vocalization by Rat Pups and Directs Order of Maternal Retrieval
J. Michael Bowers,1 Miguel Perez-Pouchoulen,4,5 N. Shalon Edwards,3 and Margaret M. McCarthy1,2,3
Departments of 1Physiology and 2Psychiatry, and 3Department of Pharmacology and Program in Neuroscience, University of Maryland School of Medicine,
Baltimore, Maryland 21201, and 4Centro de Investigaciones Cerebrales and 5Doctorado en Neuroetología, Universidad Veracruzana, 91000 Xalapa, Me´xico

The FOXP2 gene is central to acquisition of speech and language in humans and vocal production in birds and mammals. Rodents communicate via ultrasonic vocalizations (USVs) and newborn pups emit distress USVs when separated from their dam, thereby facilitating their retrieval. We observed that isolated male rat pups emitted substantially more USV calls and these were characterized by a significantly lower frequency and amplitude compared with female rat pups. Moreover, the dam was more likely to first retrieve male pups back to the nest, then females. The amount of Foxp2 protein was significantly higher in multiple regions of the developing male brain compared with females and a reduction of brain Foxp2 by siRNA eliminated the sex differences in USVs and altered the order of pup retrieval. Our results implicate Foxp2 as a component of the neurobiological basis of sex differences in vocal communication in mammals.
We extended these observations to humans, a species reported to have gender differences in language acquisition, and found the amount of FOXP2 protein in the left hemisphere cortex of 4-year-old boys was significantly lower than in age-matched girls.

Introduction
Effective communication between conspecifics is essential to fitness at both the individual and species level. Bird song has proven particularly valuable because of the profound sex differences exhibited

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