Summary: A mouse study identifies two groups of neurons in the posterior amygdala that act like behavioral “on-off switches” by communicating with the hypothalamus to control male mating and aggression.
Source: NYU Langone Health
Researchers report that two distinct sets of nerve cells in the posterior amygdala regulate male sexual and aggressive behaviors by sending signals to different regions of the hypothalamus. One population targets the medial preoptic nucleus (MPN) and is tied to mating, while the other targets the ventrolateral part of the ventromedial hypothalamus (VMHvl) and is associated with aggression.
A team led by scientists at NYU Grossman School of Medicine observed how manipulating these amygdala-to-hypothalamus pathways affected male mice. When activity in the MPN-projecting amygdala cells (MPN-signaling cells) was suppressed, males had difficulty mating. Conversely, enhancing activity in those same neurons drove persistent courtship behavior, including repeated advances toward unreceptive females—behavior not typically seen in control animals.
Similarly, reducing activity of VMHvl-projecting amygdala cells (VMHvl-signaling cells) cut the frequency of attacks on unfamiliar males roughly in half. Activating these neurons produced exaggerated aggression: treated males not only attacked unfamiliar males more often but in some cases also attacked their female partners and familiar males.
“Our findings provide new insights into the crucial role played by the posterior amygdala in driving male social behaviors like sex and aggression,” says lead author Takashi Yamaguchi, PhD, a postdoctoral fellow at NYU Langone Health and its Neuroscience Institute.
Previous work had established the hypothalamus as a central regulator of mating and fighting, and researchers had already identified key hypothalamic regions—the MPN for sexual behavior and the VMHvl for aggression. This new study is the first to isolate two separate populations of estrogen receptor–expressing cells in the posterior amygdala (PA Esr1+ cells) that provide major excitatory input to those hypothalamic targets and appear necessary and sufficient to drive the corresponding behaviors.
The investigators recorded neural activity from more than 100 male mice during natural social interactions, including mounting and male–male confrontations. They measured baseline firing patterns across the animals’ daily activity and found that MPN-projecting cells were most active during sexual behavior, while VMHvl-projecting cells were most active during aggressive encounters. The team then used targeted suppression and activation of each cell group and quantified how these manipulations altered the frequency of mounting and attacking in standard behavioral tests.
“Our new understanding of which cells prompt sexual and aggressive behaviors should help us choose better brain targets as we design future treatments for psychiatric disorders,” says senior study investigator Dayu Lin, PhD, an associate professor at NYU Langone and its Neuroscience Institute.
While the results point to a powerful influence of the posterior amygdala on male social behavior, the authors emphasize caution about generalizing these findings to humans. The posterior amygdala’s full anatomical and functional complexity is still being mapped, and further research is needed to clarify how these circuits operate in female animals and whether comparable circuits exist in human brains.
Methodologically, the study combined in vivo neuronal recording with circuit-specific manipulations and behavioral assays to link cell-type–specific activity to concrete changes in social behavior. The two PA subpopulations differed not only in their downstream connectivity but also in gene expression and in vivo response patterns, strengthening the conclusion that they play distinct roles in mating versus fighting.
Funding: This research was supported by National Institutes of Health grants R01MH101377, R21MH105774, R01HD092596, and U19NS107616.
In addition to Takashi Yamaguchi and Dayu Lin, contributors from NYU Langone included Dongyu Wei, PhD; Soomin Song, PhD; and Nicolas Tritsch, PhD. Additional support was provided by Byungkook Lim, PhD, at the University of California San Diego.
About this neuroscience research article
Source: NYU Langone Health
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Original Research: Closed access. Title: “Posterior amygdala regulates sexual and aggressive behaviors in male mice.” Authors: Takashi Yamaguchi, Dongyu Wei, Soomin C. Song, Byungkook Lim, Nicolas X. Tritsch & Dayu Lin. Published in Nature Neuroscience.
Abstract
Posterior amygdala regulates sexual and aggressive behaviors in male mice
Sexual and aggressive behaviors are fundamental to animal survival and reproduction. The medial preoptic nucleus (MPN) and the ventrolateral part of the ventromedial hypothalamus (VMHvl) are essential regions for male sexual and aggressive behaviors, respectively. While several inhibitory inputs to the VMHvl and MPN have been identified, the extrahypothalamic excitatory inputs that drive these social behaviors were not well defined. This study identifies estrogen receptor alpha (Esr1)-expressing cells in the posterior amygdala (PA) as a principal source of excitatory input to the hypothalamus and as key mediators of mating and fighting in male mice. Two largely distinct PA subpopulations differ in their connectivity, gene expression, in vivo response properties, and behavioral relevance. MPN-projecting PA Esr1+ cells become active during mating and are both necessary and sufficient for male sexual behavior. VMHvl-projecting PA Esr1+ cells are activated during intermale aggression and promote attacking behavior. These findings position the posterior amygdala as a central node in neural circuits that control male reproduction and aggression.