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Digging Deep into the Brain Sheds Light on Social Behavior

07/22/2014
Janelle Weaver, Ph.D.

A new method called fiber photometry allows for direct observation of brain activity during behavior, capturing a fundamental and previously inaccessible dimension of mammalian neural circuit dynamics. Read more... .


Impaired social interaction is a hallmark of several psychiatric disorders, including autism, schizophrenia, depression, and social anxiety. But relatively little is known about the neural circuitry that goes awry in these disorders.

Fiber photometry of neural dynamics during social interaction
To address this question, Karl Deisseroth of Stanford University and his team developed a technique called fiber photometry, which uses a single optical fiber to simultaneously stimulate neuronal activity and record responses in deep brain structures of freely moving mice. As reported in Cell, this method is sensitive enough to detect activity changes in cell bodies as well as axonal fibers, enabling researchers to identify circuit-based targets related to impaired social interaction and other neuropsychiatric disease-related symptoms.

“For me, it is particularly exciting since I see patients in my clinic with social behavior dysfunction, and we have been working toward understanding this behavior for a long time,” Deisseroth said.

In the new study, the researchers used fiber photometry to record the activity of neurons expressing a genetically encoded calcium indicator, which causes neurons to fluoresce when activated. They measured the fluorescence emitted by cell bodies in the ventral tegmental area (VTA)—a brain region that responds to reward—as well as VTA projections to another reward-related brain region called the nucleus accumbens (NAc). When female mice interacted with each other, a larger proportion of total calcium peak activity occurred for VTA-to-NAc projections than for cell bodies, suggesting that these projections more selectively encode social interaction.

Using optogenetics, the researchers delivered blue or yellow light through the optical fiber to activate or inhibit, respectively, VTA neurons that were genetically modified to express light-sensitive proteins. Activation of VTA neurons caused an increase in the investigative behavior of female mice toward a female stranger mouse placed in the same cage, while inhibition of these neurons caused a decrease in social interaction. Moreover, activation of VTA cells that specifically projected to the NAc sufficed to increase social interaction. The findings demonstrate how fiber photometry and optogenetics can complement each other to provide insights into the neural basis of behavior.

“Fiber photometry is designed to be generalizable and can be applied to target any well-defined, long-range projection in the mammalian brain,” Deisseroth said. “We will continue to use the methods to more deeply understand a range of complex behaviors.”

Reference

Gunaydin LA, Grosenick L, Finkelstein JC, Kauvar IV, Fenno LE, Adhikari A, Lammel S, Mirzabekov JJ, Airan RD, Zalocusky KA, Tye KM, Anikeeva P, Malenka RC, Deisseroth K. Natural neural projection dynamics underlying social behavior. Cell. 2014 Jun 19;157(7):1535-51. doi: 10.1016/j.cell.2014.05.017.