Smell Tells Intruder Mice How To Behave

Summary: A new study reports that a genetically specific cluster of hypothalamic cells is wired to the olfactory system and responds only when a male mouse enters another male’s cage.

Source: Cell Press.

Male mice appear to be precisely wired to know when they are intruders in another male’s territory, according to a study published June 23 in Cell Reports. The smell gives it away. But this study found that a genetically specific cluster of hypothalamic cells is wired to the olfactory system and responds only when a male mouse enters another male’s cage.

“There seems to be a specific part of the brain that says, yeah, this is someone’s house, and you need to act accordingly,” says lead investigator Larry Zweifel, assistant professor of pharmacology at the University of Washington.

The hypothalamus, which is known to be the seat of social behavior in the brain, may contain additional sets of distinct cells wired to respond to other specific social contexts. Together, these signals tell an animal how to behave. The study, one of the first to look at what drives the behavior of subordinate mice rather than aggressors, could help researchers better understand disorders in social behavior in humans. For instance, individuals with autism, schizophrenia, depression, and social anxiety all experience disruptions in social behavior.

“The basic circuitry that regulates social function in a mouse is essentially the same as it is in humans,” says Zweifel. “We’re studying these discrete cells in the parts of the brain that regulate social behavior in mice to get some insight into where things go wrong to cause social behavioral deficits.”

Zweifel’s team came across the cells–neurons in the ventral premammillary nucleus of the hypothalamus–because they are genetically programmed to release dopamine, a neurotransmitter his team studies. It turns out that they don’t release dopamine. But the team couldn’t help but be intrigued when they saw that these cells were strongly activated only to male smells.

The team followed up by exposing male mice to a set of social contexts. A control group experienced no encounter. Others were either intruders into a cage occupied by either a male or female or were intruded upon in their own residence by either a male or female. The cells were activated in intruders only upon entering the cage of a male resident. Odors from both the resident animal and the cage, which contained bedding marked by the resident’s urine, drove the cellular activity.

Most studies have focused on aggressive behavior because of its relevance to human social struggles, but in this social context, an intruder into another’s cage is by definition a subordinate. “The parts of the brain that control aggression have been fairly well established,” says Zweifel. “But what’s it like if you’re the animal that’s encroaching into another’s territory?”

Zweifel’s team found that the intruder mouse’s immediate impulse is to get more information. “They sniff and explore, like dogs in a park,” says Zweifel. “Who are you, and are you fun to play with?”

Image shows a drawing of mice and a brain.
This visual abstract depicts the findings of Soden et al., who characterize a population of neurons in the ventral premammillary nucleus of the hypothalamus that are genetically defined as dopaminergic but that do not release detectable dopamine. These neurons are activated in specific social contexts and function via glutamate release to regulate male same sex social interactions. NeuroscienceNews.com image is credited to Soden et al./Cell Reports 2016.

Animals sniff and explore in other social situations, too, but these specific cells have nothing to do with it. “If you introduce a male into a female’s cage, social investigation goes through the roof,” says Zweifel. “But these cells aren’t activated in this context.”

To pin down the exact role of these cells, Zweifel’s team inhibited them so that they would not be activated. This reduced exploration in male intruders. They also activated these cells artificially using optogenetics, the genetic engineering of cells to respond to light input. Activation increased exploration in males, causing them to sniff and explore mice they’d known since birth as if they were strangers.

In females, however, the cells were not activated by same-sex odorants, suggesting that these cells are not wired to control social exploration in females. “We don’t know what they’re doing in females yet,” says Zweifel.

While sensory input induces these hypothalamic neurons to fire, the social control happens downstream in the medial amygdala and other regions of the hypothalamus. Zweifel’s team intends to look there next to learn more about how social behavior is wired in the brain.

About this neuroscience research article

Funding: This work was supported by the National Institutes of Health.

Source: Joseph Caputo – Cell Press
Image Source: This NeuroscienceNews.com image is credited to Soden et al./Cell Reports 2016.
Original Research: Full open access research for “Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior” by Marta E. Soden, Samara M. Miller, Lauren M. Burgeno, Paul E.M. Phillips, Thomas S. Hnasko, and Larry S. Zweifel in Cell Reports. Published online June 23 2016 doi:10.1016/j.celrep.2016.05.067

Cite This NeuroscienceNews.com Article

[cbtabs][cbtab title=”MLA”]Cell Press. “Smell Tells Intruder Mice How To Behave.” NeuroscienceNews. NeuroscienceNews, 23 June 2016.
<https://neurosciencenews.com/smell-mouse-behavior-4551/>.[/cbtab][cbtab title=”APA”]Cell Press. (2016, June 23). Smell Tells Intruder Mice How To Behave. NeuroscienceNew. Retrieved June 23, 2016 from https://neurosciencenews.com/smell-mouse-behavior-4551/[/cbtab][cbtab title=”Chicago”]Cell Press. “Smell Tells Intruder Mice How To Behave.” https://neurosciencenews.com/smell-mouse-behavior-4551/ (accessed June 23, 2016).[/cbtab][/cbtabs]


Abstract

Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior

Highlights

•A group of neurons in the ventral premammillary nucleus express dopamine markers
•These neurons are activated in male intruder, but not resident, mice
•These neurons regulate same-sex social behavior in specific contexts
•These neurons function via glutamate release, but do not release detectable dopamine

Summary
Nearly all animals engage in a complex assortment of social behaviors that are essential for the survival of the species. In mammals, these behaviors are regulated by sub-nuclei within the hypothalamus, but the specific cell types within these nuclei responsible for coordinating behavior in distinct contexts are only beginning to be resolved. Here, we identify a population of neurons in the ventral premammillary nucleus of the hypothalamus (PMV) that are strongly activated in male intruder mice in response to a larger resident male but that are not responsive to females. Using a combination of molecular and genetic approaches, we demonstrate that these PMV neurons regulate intruder-specific male social behavior and social novelty recognition in a manner dependent on synaptic release of the excitatory neurotransmitter glutamate. These data provide direct evidence for a unique population of neurons that regulate social behaviors in specific contexts.

“Genetic Isolation of Hypothalamic Neurons that Regulate Context-Specific Male Social Behavior” by Marta E. Soden, Samara M. Miller, Lauren M. Burgeno, Paul E.M. Phillips, Thomas S. Hnasko, and Larry S. Zweifel in Cell Reports. Published online June 23 2016 doi:10.1016/j.celrep.2016.05.067

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