Summary: Researchers have identified a specific neural circuit that detects male pheromone signals involved in inter-male aggression.
Source: Chinese Academy of Sciences
In a study published in Neuron, scientists from Dr. XU Xiaohong’s laboratory at the Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, describe a previously uncharacterized neural pathway that detects male pheromone cues relevant to male–male aggression.
Innate social behaviors are essential for survival and species propagation. Before initiating mating or fighting, animals must accurately identify the sex of another animal. For example, males typically pursue mating with females but will show aggression toward other males. Olfactory cues, especially those processed by the vomeronasal organ (VNO), play a central role in this sex recognition.
Past work showed that disabling VNO function—by knocking out the trpc2 gene—reduces inter-male aggression and increases inappropriate mating behaviors toward both male and female intruders. Those findings indicate that VNO-derived olfactory signals are critical for sex discrimination and for guiding appropriate social responses.
Although the hypothalamus is known to orchestrate innate behaviors such as mating and aggression, how hypothalamic neurons receive and translate sex-specific chemosensory information from the VNO into distinct behavioral outputs has remained unclear.
Using in vivo calcium imaging in freely behaving mice, the researchers found a distinct population of dopamine transporter–expressing neurons (DAT+) in the ventral premammillary nucleus (PMv). These PMvDAT neurons exhibited strong, selective responses when male mice sampled urine from intact males, but showed little or no response to urine from castrated males, females, newborns, or other species such as rats.
Functional manipulations confirmed the causal role of these neurons. Chemogenetic inhibition of PMvDAT neurons disrupted male mice’s ability to recognize male urine and significantly reduced their aggressive behaviors toward male intruders. Conversely, activating PMvDAT neurons heightened aggression and increased urine-marking behavior toward male conspecifics.
To determine whether VNO signaling drives PMvDAT responses, the team examined trpc2 knockout mice, in which VNO function is disrupted. PMvDAT neuron responses to male urine were substantially diminished in these knockout males, demonstrating VNO dependence for the PMvDAT tuning to male-specific cues.
Combining viral tracing, calcium recordings, and chemogenetic tools, the researchers mapped the pathway that conveys male-relevant chemosensory information. They identified a relay through the ventral bed nucleus of the stria terminalis (v-BNST) that transmits VNO-derived signals to PMvDAT neurons. This v-BNST → PMvDAT pathway appears to be a critical conduit for male-specific olfactory information relevant to inter-male aggression.
Taken together, these findings reveal a hypothalamic node—PMvDAT neurons—that selectively encodes male conspecific signals and links sex-specific chemosensory input to aggressive behavioral output. The study clarifies how VNO-dependent pheromone cues are routed through the BNST to the hypothalamus to trigger appropriate, sexually dimorphic social behaviors.
This work advances our understanding of the neural circuit mechanisms that underlie sex-specific olfactory processing and the control of innate social behaviors such as urine marking and aggression. By pinpointing the PMvDAT population and the v-BNST relay, the study provides a clearer map of how sensory signals are translated into context-appropriate actions in male mice.
About this neuroscience research article
Source:
Chinese Academy of Sciences
Contacts:
LIU Jia – Chinese Academy of Sciences
Image Source:
The image is in the public domain.
Original Research: Open access
“Specific Hypothalamic Neurons Required for Sensing Conspecific Male Cues Relevant to Inter-male Aggression” by XU Xiaohong et al. Neuron.
Abstract
Specific Hypothalamic Neurons Required for Sensing Conspecific Male Cues Relevant to Inter-male Aggression
Highlights
• PMv DAT+ neurons selectively respond to urine from gonad-intact male conspecifics
• v-BNST relays male-relevant chemosensory information from the VNO to PMv DAT+ neurons
• Inhibiting PMv DAT+ neurons eliminates male urine preference and reduces attack behavior
• Activating PMv DAT+ neurons enhances urine marking and aggressive responses
Summary
The hypothalamus coordinates innate social behaviors, but the mechanisms by which sex-specific sensory cues from conspecifics are transformed into behavioral commands were not fully understood. In this study, in vivo recordings revealed that DAT-expressing neurons in the ventral premammillary nucleus (PMv) selectively respond to male urine signals in a VNO-dependent manner. Retrograde trans-synaptic tracing identified a group of neurons in the bed nucleus of the stria terminalis (BNST) that relay male-relevant signals from the VNO to PMv. Functional tests showed that silencing PMv DAT+ neurons abolishes preference for male urine and reduces inter-male attacks, while activating these neurons promotes urine marking and aggression. These results identify PMv DAT+ neurons as a hypothalamic hub that converts sex-related chemo-signals into recognition and action, illuminating a key circuit for sexually dimorphic social behavior.