Star-shaped cells may play role in how your brain merges info

Astrocytes may be a key player in the brain’s ability to process external and internal information simultaneously, according to a new study.

Long thought of as “brain glue,” the star-shaped cells called astrocytes are members of a family of cells found in the central nervous system called glial that help regulate blood flow and synaptic activity, keep neurons healthy, and play an important role in breathing.

Despite this growing appreciation for astrocytes, much remains unknown about the role these cells play in helping neurons and the brain process information.

“We believe astrocytes can add a new dimension to our understanding of how external and internal information is merged in the brain,” says Nathan Smith, associate professor of neuroscience at the Del Monte Institute for Neuroscience at the University of Rochester.

“More research on these cells is necessary to understand their role in the process that allows a person to have an appropriate behavioral response and also the ability to create a relevant memory to guide future behavior.”

The way our body integrates external with internal information is essential to survival. When something goes awry in these processes, behavioral or psychiatric symptoms may emerge.

Smith and coauthors point to evidence that astrocytes may play a key role in this process. Previous research has shown astrocytes sense the moment neurons send a message and can simultaneously sense sensory inputs. These external signals could come from various senses such as sight or smell.

Astrocytes respond to this influx of information by modifying their calcium Ca2+ signaling directed towards neurons, providing them with the most suitable information to react to the stimuli.

The authors hypothesize that this astrocytic Ca2+ signaling may be an underlying factor in how neurons communicate and what may happen when a signal is disrupted. But much is still unknown in how astrocytes and neuromodulators, the signals sent between neurons, work together.

“Astrocytes are an often-overlooked type of brain cell in systems neuroscience,” Smith says. “We believe dysfunctional astrocytic calcium signaling could be an underlying factor in disorders characterized by disrupted sensory processing, like Alzheimer’s and autism spectrum disorder.”

Smith has spent his career studying astrocytes. As a graduate student at the University of Rochester School of Medicine and Dentistry, Smith was part of the team who discovered an expanded role for astrocytes. Apart from absorbing excess potassium, astrocytes themselves could cause potassium levels around the neuron to drop, halting neuronal signaling. This research showed, for the first time, that astrocytes did more than tend to neurons, they also could influence the actions of neurons.

“I think once we understand how astrocytes integrate external information from these different internal states, we can better understand certain neurological diseases. Understanding their role more fully will help propel the future possibility of targeting astrocytes in neurological disease,” Smith says.

The communication between neurons and astrocytes is far more complicated than previously thought. Evidence suggests that astrocytes can sense and react to change—a process that is important for behavioral shifts and memory formation.

The study authors believe discovering more about astrocytes will lead to a better understanding of cognitive function and lead to advances in treatment and care.

The study appears in Trends in Neuroscience.

Additional coauthors are from the University of Copenhagen.

The National Institutes of Health, the National Science Foundation, the European Union under the Marie Skłodowska-Curie Fellowship, the ONO Rising Star Fellowship, the Lundbeck Foundation Experiment Grant, and the Novo Nordisk Foundation supported the work.

Source: University of Rochester

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Key neurons in mice ‘learn’ to sniff out threats

Researchers are finding new clues to how the olfactory sensory system aids in threat assessment and have found neurons that “learn” if a smell is a threat.

Whether conscious of it or not, when entering a new space, we use our sense of smell to assess whether it is safe or a threat. In fact, for much of the animal kingdom, this ability is necessary for survival and reproduction.

“We are trying to understand how animals interact with smell and how that influences their behavior in threatening social and non-social contexts,” says senior author Julian Meeks, principal investigator of the Chemosensation and Social Learning Laboratory at the Del Monte Institute for Neuroscience at the University of Rochester.

“Our recent research gives us valuable tools to use in our future work and connects specific sets of neurons in our olfactory system to the memory of threatening smells.”

Sniffing out threats

Smell may guide how the brain responds to a social threat. In mice, the researchers identified a specific set of neurons in the accessory olfactory system that can learn the scent of another mouse that is a potential threat. The research appears in the Journal of Neuroscience.

“We knew that territorial aggression increases in a resident male mouse when it is repeatedly introduced to the same male,” says Kelsey Zuk, first author of the research.

“Previous research has shown this behavior is guided by social smells—our research takes what we know one step further. It identifies where in the olfactory system this is happening. We now know plasticity is happening between the neurons, and the aggression between the male mice may be driven by the memory formed by smell.”

The researchers found that “inhibitory” neurons (nerve cells that act by silencing their synaptic partners) in an area of the brain responsible for interpreting social smells become highly active and change their function when males repeatedly meet and increase their territorial aggression.

By disrupting the neurons associated with neuroplasticity—learning—in the accessory olfactory bulb, the researchers revealed that territorial aggression decreased, linking changes to cellular function in the pheromone-sensing circuity of the brain to changes in behavioral responses to social threats.

“It abolished the ramping aggression that is typically exhibited,” says Zuk. “It indicates that this early sensory inhibitory neuron population plays a critical role in regulating the behavioral response to social smells.”

Unknown smells

Threat assessment also comes when an animal navigates unknown smells. For example, the smell of a predator it has never encountered. In a second paper in eNeuro, researchers found that a novel predator smell, i.e. the smell of a snake to a mouse, caused the animal to engage in a threat assessment behavior—neither acting “fearful” nor “safe.”

“This offers clues into how chemical odors given off by predators stimulate threat assessment in the brain,” says Jinxin Wang, first author of a paper. “Identifying changes in patterns of animal behavior helps us better understand how threatening smells are processed in the brain.”

The researchers used video tracking to observe the movement and posture of mice exploring familiar environments with different odors—like other mice and snakes. Wang and colleagues developed a hybrid machine learning approach that helped them to uncover that mice respond to novel predator odors in ways that were unique and distinguishable from how mice reacted to non-predator odors. These behaviors were neither fearful nor safe but rather a state of assessment.

“These findings offer new clues into how smells impact social behavior and what it may mean for survival, but this study also offers new tools that will propel this science forward,” says Meeks.

“We combined methods that had known limitations to improve the accuracy, information depth, and human-interpretability of the collected data. We think this approach will be valuable for future research into how the blends of chemical odorants given off by predators stimulate threat assessment in the brain.”

Additional coauthors of the Journal of Neuroscience research are from the University of Rochester and the University of Florida. Support for the research came from the National Institutes of Health.

Additional coauthors of the eNeuro research are from the University of Texas Southwestern Medical Center. Support for the research came from the National Institute on Deafness and Other Communication Disorders.

Source: University of Rochester

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