Stanford University investigators link socialising behaviour with specific neural circuits

Investigators at Stanford University have linked a particular brain circuit in mice to the mammals’ tendency to interact socially in a new study Natural neural projections dynamics underlying social behaviour (published June 19 in Cell). Stimulating this social circuit instantly increases a mouse’s approach to know a strange mouse, while inhibiting it shuts down such a drive to socialize with an unknown other.

The study’s senior author, Karl Deisseroth, MD, PhD, a professor of bioengineering and of psychiatry and behavioural sciences, said the new findings may throw light on pathologies of impaired social interaction such as autism, social anxiety, schizophrenia and depression. The findings are also significant in that they highlight not merely the role of one or another brain chemical, as pharmacological studies tend to do, but rather the specific components of brain circuits involved in a complex behavior. A combination of cutting-edge techniques developed in Deisseroth’s laboratory permitted unprecedented analysis of how brain activity controls behaviour.

Deisseroth pioneered a brain-exploration technique known as optogenetics; a process that selectively introduces light-receptor molecules to the surfaces of particular nerve cells in a living animal’s brain and then carefully positioning an ultra-thin optical fiber (connected to a laser diode at the other end) pointing to the circuit under investigation, so that the photosensitive cells can be remotely stimulated or inhibited at the turn of a light switch while the animal remains free to move around in its cage. It is like having an “on/off” switch for a specific brain circuit.

Using optogenetics and other methods Deisseroth and associates were able to both manipulate and monitor activity in specific nerve-cell clusters, and the fiber tracts connecting them, in mice’s brains in real time while the animals were exposed to either murine newcomers or inanimate objects in various laboratory environments. The mice’s behavioral responses were captured by video and compared with simultaneously recorded brain-circuit activity.

The team first examined the relationship between the mice’s social interactions and a region in the brain stem called the ventral segmental area (VTA). The VTA is a key node in the brain’s reward circuitry and transmits signals to other centers throughout the brain via tracts of fibers that secrete chemicals, including dopamine, at contact points abutting nerve cells within these faraway centers. When dopamine lands on receptors on those nerve cells, it can set off signaling activity within them.

Abnormal activity in the VTA has been linked to drug abuse and depression. However, much less is known about this brain center’s role in social behavior, and it had not previously been possible to observe or control activity along its connections during social behaviour. The current study used mice whose dopaminergic, VTA nerve cells had been bioengineered to express optogenetic control proteins that could set off or inhibit signalling in the cells in response to light. They observed that enhancing activity in these cells increased a mouse’s penchant for social interaction. When a newcomer was introduced into its cage, it came, it saw, it sniffed. Inhibiting the dopaminergic VTA cells had the opposite effect: The host lost much of its interest in the guest. The effect appeared to be specific for social interaction as it did not change their behaviour of exploring and generally moving around.

Finding out exactly which dopaminergic projections from the VTA, traveling to which remote brain structures, were carrying the signals that generate exploratory social behaviour  are extremely weak and required designing a new monitoring methodology. Deisseroth’s team developed a highly sensitive technology capable of plucking these tiny signals out of the surrounding neural noise. The new technique, called fiber photometry, is a sophisticated way of measuring calcium flux, which invariably accompanies signaling activity along the fibers projecting from nerve cells.

Using a combination of optogenetics and fiber photometry, the investigators were able to demonstrate that a particular tract projecting from the VTA to a mid-brain structure called the nucleus accumbens was the relevant conduit carrying the impetus to social interaction in the mice.

“Every behaviour presumably arises from a pattern of activity in the brain, and every behavioural malfunction arises from malfunctioning circuitry,” said Deisseroth.  “The ability, for the first time, to pinpoint a particular nerve-cell projection involved in the social behaviour of a living, moving animal will greatly enhance our ability to understand how social behaviour operates, and how it can go wrong.”

You can find out more about this fascinating study by going to the paper abstract here Abstract and seeing the press release below.

Source: Press Release by Bruce Goldman.

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