Sexually Dimorphic Neurons in the Ventromedial Hypothalamus Govern Mating in Both Sexes and Aggression in Males

Abstract

SUMMARY Sexual dimorphisms in the brain underlie behavioral sex differences, but the function of individual sexually dimorphic neuronal populations is poorly understood. Neuronal sexual dimorphisms typically represent quantitative differences in cell number, gene expression, or other features, and it is unknown if these dimorphisms control sex-typical behavior in one sex exclusively or in both sexes. The progesterone receptor (PR) controls female sexual behavior, and we find many sex differences in number, distribution, or projections of PR-expressing neurons in the adult mouse brain. We have ablated one such PR-expressing neuronal population located in the ventromedial hypothalamus (VMH) using a novel genetic strategy. Ablation of these neurons in females greatly diminishes sexual receptivity. Strikingly, the corresponding ablation in males reduces mating and aggression. Our findings reveal the functions of a molecularly-defined, sexually dimorphic neuronal population in the brain. Moreover we show that sexually dimorphic neurons can control distinct sex-typical behaviors in both sexes.

Internal States and Behavioral Decision-Making: Toward an Integration of Emotion and Cognition

“…Time-resolved optogenetic inhibition of Esr1 þ neurons interrupted ongoing attack (Fig. 5F,G), indicating that their activity is required during this consummatory phase of an aggressive encounter, confirming and extending earlier loss-of-function studies (Lin et al 2011;Sano et al 2013;Yang et al 2013). 9 Finally, preliminary experiments using optogenetic phototagging (Lima et al 2009) to identify Esr1 þ neurons in multi-electrode recordings indicate that these cells exhibit increased spiking rates during attack ( Fig.…”

“…Optogenetic stimulation experiments should be interpreted with caution, because artificial patterns of activation could produce abnormal behaviors. Male mounting has been suggested to be a "default" social behavior (Stowers 9 Previous studies indicated that killing progesterone receptor (PR)-expressing neurons in VMHvl (which overlap Esr1 þ neurons by 90%) partially reduced aggression (Yang et al 2013), as did RNAi-mediated knockdown of Esr1 in VMHvl (Sano et al 2013). However, because of the long delay between the manipulation and behavioral testing (2-3 wk), these studies could not distinguish a permissive requirement for VMHvl, e.g., in the detection of chemosensory cues essential for male -male recognition, from a requirement during attack per se.…”

“…et al 2002); thus, low-intensity stimulation of VMHvl Esr1 þ neurons could lead to mounting by default. Nevertheless, genetic ablation of progesterone receptor (PR)-expressing VMHvl neurons (Yang et al 2013) (which highly overlap Esr1 þ neurons) or knockdown of Esr1 mRNA in VMHvl (Sano et al 2013) both significantly reduced male mounting toward females. These data are consistent with the idea that VMHvl does play a role in normal male sexual behavior.…”

Behavioral and Physiological Effects of a Novel Kappa-Opioid Receptor-Based DREADD in Rats

“…Additionally, KORDs can be used in combination with the original muscarinic-based DREADDs to permit bi-directional control over either the same or different neural projections as described in Vardy et al (2015). Finally, the dual-virus approach is versatile; one could replace the DIO-KORD construct with other Credependent viruses (eg, Tian et al, 2012;Yang et al, 2013) to monitor and manipulate neural projections during complex behaviors in rats.…”

Dopaminergic Dynamics Contributing to Social Behavior

“…Several cortical and subcortical brain regions have been implicated in controlling social behavior, such as the prefrontal cortex, amygdala, striatum, dorsal raphe, and hypothalamus (Gingrich et al 2000;Young et al 2001;Leypold et al 2002;Robinson et al 2002;Liu and Wang 2003;Young and Wang 2004;Curtis and Wang 2005;Aragona et al 2006;Lin et al 2011;Robinson et al 2011;Dölen et al 2013;Yang et al 2013;Felix-Ortiz and Tye 2014;Hong et al 2014;Unger et al 2015). In rodents, the majority of these studies have focused on sociosexual behaviors, such as pair bonding, aggression, and other behaviors related to sexual competition.…”