Males and females of many sexually reproducing species behave differently during mating or towards the young. Despite numerous documentation of sex differences in the brain at the cellular and molecular levels, how such sex differences relate to sexually dimorphic display of behaviors remain unclear.

In a recent study published in Nature Communications entitled “Medial preoptic area in mice is capable of mediating sexually dimorphic behaviors regardless of gender”, WEI and colleagues in Dr. XU Xiaohong’s lab showed unexpectedly that a well-known sexually dimorphic brain nucleus can drive both male-typical and female-typical behaviors.

The medial preoptic area (mPOA) locates to the anterior tip of the hypothalamus at the base of the brain and is known to be larger in males than females in many species, including the human. In addition, the mPOA harbors sex-specific gene expression and connectivity patterns. In this study, by recording neural activities of the mPOA, in particular mPOA neurons that express estrogen receptor  (Esr1), during male-typical mount and female-typical pup retrieval, Wei and colleagues first show that mPOA neuronal activities strongly correlate with sexually dimorphic display of mount and pup retrieval. Strikingly, optogenetic activation of the mPOA can drive both mount and pup retrieval at similar levels in male and female, indicating that the mPOA in both sexes contain neural substrates to activate these behaviors. Furthermore, ablation of mPOA Esr1+ neurons essentially abolished sex differences in the display of mount and pup retrieval. Finally, acute inhibition of activities of mPOA Esr1+ neurons disrupts mount and pup retrieval. Together these results suggest a fundamental bi-sexual layout of the brain for sex-specific behaviors, where sexually dimorphic activation of neural circuits that exist in both sexes leads to sex biased display of behaviors.

This study was performed by WEI Yichao in collaboration with Wang Shaoran under the supervision of Dr. XU Xiaohong, in the laboratory of neural basis of innate behaviors at the Institute of Neuroscience, CAS. This work was supported by grants from the National Nature Science Foundation of China (31471065), Ministry of Science and Technology office China 973 program (2015CB559201), the Thousand Young Talents Program of China, the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB02030005), and as part of the CAS interdisciplinary innovation team.

mPOA Esr1+ neurons mediate sexually dimorphic display of behaviors：When given a female as the stimulus, males are more likely to display stereotyped mounting than females during behavioral tests. When given scattered pups as the stimulus, females are more likely to display pup retrieval behavior than males. a. By injecting AAVs encoding Cre-inducible Gcamp6s, a genetically encoded Ca2+ indicator, into the mPOA of Esr1-Cre animals, we find that neural activities of mPOA Esr1+ neurons strongly correlate with sexually dimorphic display of mounting and pup retrieval. b. By injecting AAVs encoding Cre-inducible ChR2, a genetically encoded light sensitive cation channel, into the mPOA of Esr1-Cre animals, we find that optogenetic activation of mPOA Esr1+ neurons elicits similar display of mounting and pup retrieval in both sexes. c. By injecting AAVs encoding Cre-inducible GtACR1, a genetically encoded light sensitive chloride channel, into the mPOA of Esr1-Cre animals, we find that acutely inhibiting mPOA Esr1+ neurons significantly disrupts the display of mounting in males and pup retrieval in females compared to the control animals.