Abstract
Acquisition of social proficiency entails behavioral adaptations to social experience, including both behavioral flexibility and inhibition of behaviors inappropriate in specific social contexts. Here, we investigated the contributions of testosterone and ΔFosB, a transcription factor linked to experience-dependent neural plasticity, to the adolescent maturation of social proficiency in male-female social interactions. To determine whether pubertal testosterone organizes circuits underlying social proficiency, we first compared behavioral adaptations to sexual experience in male Syrian hamsters that were deprived of testosterone during puberty (prepubertal castration; NoT@P) to those of males deprived of testosterone for an equivalent period of time in adulthood (postpubertal castration; T@P). All males were given testosterone replacement in adulthood for two weeks before sexual behavior testing, where males were allowed to interact with a receptive female once per week for five consecutive weeks. T@P males showed the expected decrease in ectopic (mis-directed) mounts with sexual experience, whereas NoT@P males did not. In addition, sexual experience induced FosB gene products expression in the infralimbic cortex (IL) in T@P, but not NoT@P, males. Over-expression of ΔFosB via an adeno-associated viral vector in the IL of NoT@P males prior to sexual behavior testing was sufficient to produce a behavioral phenotype similar to that of experienced T@P males. Finally, over-expression of ΔFosB in IL increased the density of immature spines on IL dendrites. Our findings provide evidence that social proficiency acquired through sexual experience is organized by pubertal testosterone through the regulation of ΔFosB in the IL, possibly through increasing synaptic lability.
Significance Statement Social proficiency is the ability to make experience-dependent behavioral adaptations that enhance the success of subsequent social interactions. In male rodents, social proficiency in adulthood is programmed by the pubertal rise in testosterone, but neuroendocrine mechanisms underlying this behavioral plasticity are not understood. We show that pubertal testosterone is necessary for both sexual proficiency and experience-dependent induction of ΔFosB in the infralimbic (IL) medial prefrontal cortex in adulthood. Furthermore, over-expression of ΔFosB in the IL increases immature dendritic spines on IL neurons and is sufficient to restore a socially proficient phenotype in males that lacked testosterone during puberty. Hormonal programming of experience-dependent regulation of prefrontal ΔFosB is a novel mechanism of adolescent development of behavioral and neural plasticity in adulthood.
Footnotes
The authors declare no competing financial interests.
This work was supported by R01 MH068764 (CLS), T32 MH0700343 (KCD), R01 MH111694 (AJR), R01 DA040621 (AJR), and F31 DA042502 (SEC).
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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