Foxp2 Mediates Sex Differences in Ultrasonic Vocalization by Rat Pups and Directs Order of Maternal Retrieval

Departments of Physiology and Psychiatry, and Department of Pharmacology and Program in Neuroscience, University of Maryland School of Medicine, Baltimore, Maryland 21201, and Centro de Investigaciones Cerebrales and Doctorado en Neuroetología, Universidad Veracruzana, 91000 Xalapa, México.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 02/2013; 33(8):3276-83. DOI: 10.1523/JNEUROSCI.0425-12.2013
Source: PubMed


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.

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    • " the polyclonal rabbit antibody to FoxP1 ( Abcam , Cambridge , MA , #ab16645 ) at 1 : 500 . Primary antibody was omitted for negative controls . Target specificity of the primary antibody for FoxP2 had been previously verified in zebra finches ( Soderstrom and Luo , 2010 ) , while the primary antibody for FoxP1 was pre - viously verified in rats ( Bowers et al . , 2013 ) . We note that the staining pattern for FoxP2 closely matched that for FoxP1 ; overlapping confocal images show coexpression of FoxP2 and FoxP1 ( see Fig . 3 ) . Following overnight incuba - tion at 4 C , sections were washed three times for 5 min each with 1X PBS , then incubated for 2 hours at room tem - perature in PBST / 1% donkey"
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    • "Our studies are the first to characterize the effect of cerebral ischemia on the USV that ordinarily occurs in a sex-specific and stimulus-specific manner in healthy rats and mice [35, 36]. In the female mouse, baseline vocalization to cage mates is readily measurable, although there is large variance in this behavior among animals. "
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    • "These distress vocalizations provide a unique biologically and socially relevant signal essential for early survival and development (Zeskind et al. 2011). Similarly, previous studies in mice and rats have used maternal separation-induced USVs as an early developmental measure of disease (Hodgson et al. 2008; Scattoni et al. 2009; Bowers et al. 2013; Brudzynski 2013). For example , Foxp2 has previously been shown to mediate sex differences in Fibroblast growth factor 17 KO mice, a putative model for schizophrenia has impaired social behavior as well as decreased maternal separation-induced USVs (Scearce-Levie et al. 2008). "
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