Sex Differences In Ultrasonic Vocalization in Rat Pups

Topics: Gender, Sex, Human brain Pages: 8 (7579 words) Published: April 23, 2015
3276 • The Journal of Neuroscience, February 20, 2013 • 33(8):3276 –3283


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.

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 by some species, leading to the discovery of the first sexually dimorphic neuroanatomical underpinnings controlling a specific behavior (Nottebohm and Arnold, 1976). Sex differences in auditory communication are prevalent in the animal kingdom (Kelley and Bass, 2010) but to date they have largely if not exclusively been identified in the context of attracting conspecific mating partners and/or defending territories. An additional critical communicative pair is the parent/offspring unit. When dependent offspring are separated from their caregiver they frequently signal their distress vocally. This is a tightly regulated contextspecific behavior that is common in a wide range of vertebrate species including birds, rodents and humans (Bell and Ainsworth, 1972; Vilberg et al., 1984; Brudzynski, 2005). To our knowledge, there has been no consideration of whether male

versus female dependents signal differently, and if so, whether this has any functional consequences.
FOXP2 is a member of the forkhead family of transcription
factors and has a highly conserved amino acid and DNA sequence Received Jan. 30, 2012; revised Dec. 6, 2012; accepted Dec. 7, 2012. Author contributions: J.M.B. and M.M.M. designed research; J.M.B., M.R.P.-P., and N.S.E. performed research; M.M.M. contributed unpublished reagents/analytic tools; J.M.B. and M.R.P.-P. analyzed data; J.M.B. and M.M.M. wrote the paper.

This work was supported by NIH Grant R01 NS050525 to M.M.M., NIH Individual Postdoctoral Fellowship (F32) MH086258 to J.M.B., and Consejo Nacional de Ciencia y Tecnología (CONACYT 205779) of Mexico to MPP. Human tissue was obtained from the NICHD Brain and Tissue Bank for Developmental Disorders at the University of Maryland, Baltimore, Maryland. Correspondence should be addressed to Dr. J. Michael Bowers at the above address. E-mail:

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