Manipulating neural circuits in mice can make social interaction more or less rewarding

Neuroscientists have new insights into why previous experiences influence future behaviors. Experiments in mice reveal that personal history, especially stressful events, influences how the brain processes whether something is positive or negative. These calculations ultimately impact how motivated a rodent is to seek social interaction or other kinds of rewards.

In a first of its kind study, Tufts University School of Medicine researchers demonstrate that interfering with the neural circuits responsible for emotional decisions can increase or decrease socially avoidant behaviors in mice, regardless of whether they had enriched or adverse experiences as pups.

The findings, published February 13 in the Journal of Neuroscience, suggest that antisocial behaviors associated with childhood neglect or related forms of abuse may result from dysfunctional dopamine signaling in the midbrain.

Many aspects of motivation involve dopamine, the neurotransmitter responsible for pleasurable feelings. When a mammal does something that enhances the chances of survival, such as eat a tasty meal or engage in sex, dopamine levels surge.

In humans (and mice), positive social interactions are generally rewarded by a burst of activity in the ventral tegmental area—a pathway of dopamine-releasing neurons. It connects the basolateral amygdala, a clump of nerves in the midbrain where emotions are processed, to the prefrontal cortex, where the brain makes critical decisions surrounding emotion and motivation.

“If people with early life stress are losing the ability to send information from parts of the brain that are needed for motivated behaviors, it made sense that we’d see less crosstalk between these two areas,” says first author Bradly Stone, who conducted the research as a Tufts postdoctoral scholar.

“The result that turned our heads was that early life stress reduces the number of dopaminergic neurons between the ventral tegmental area and basolateral amygdala, suggesting that network architecture is impaired.”

To test this hypothesis, Stone and his colleagues leveraged cutting-edge laboratory techniques that allowed them to artificially activate or silence dopamine inputs into the basolateral amygdala from the ventral tegmental area. They applied this to a classic behavioral protocol in which a mouse is given the choice to investigate chambers with either a toy or a stranger mouse.

Mice with carefree early days visited the stranger mouse as expected. However, mice that experienced maternal neglect primarily opted to do nothing or interact with the toy. This was only revealed when the investigators activated the dopaminergic neurons between the ventral tegmental area and basolateral amygdala.

Importantly, when dopaminergic neurons were turned off in animals with carefree early days, they started behaving like animals who grew up with maternal neglect.

“This experiment was a beautiful part to this story that really made me believe in the work,” says Stone. “It’s evidence that social avoidance is governed by a delicate balance of interconnected neural elements and early life stress shapes these connections in a nuanced way that impairs their ability to function.”

Neuroscientists have new insights into why previous experiences influence future behaviors. Experiments in mice reveal that personal history, especially stressful events, influences how the brain processes whether something is positive or negative. These calculations ultimately impact how motivated a rodent is to seek social interaction or other kinds of rewards.

In a first of its kind study, Tufts University School of Medicine researchers demonstrate that interfering with the neural circuits responsible for emotional decisions can increase or decrease socially avoidant behaviors in mice, regardless of whether they had enriched or adverse experiences as pups.

The findings, published February 13 in the Journal of Neuroscience, suggest that antisocial behaviors associated with childhood neglect or related forms of abuse may result from dysfunctional dopamine signaling in the midbrain.

Many aspects of motivation involve dopamine, the neurotransmitter responsible for pleasurable feelings. When a mammal does something that enhances the chances of survival, such as eat a tasty meal or engage in sex, dopamine levels surge.

In humans (and mice), positive social interactions are generally rewarded by a burst of activity in the ventral tegmental area—a pathway of dopamine-releasing neurons. It connects the basolateral amygdala, a clump of nerves in the midbrain where emotions are processed, to the prefrontal cortex, where the brain makes critical decisions surrounding emotion and motivation.

“If people with early life stress are losing the ability to send information from parts of the brain that are needed for motivated behaviors, it made sense that we’d see less crosstalk between these two areas,” says first author Bradly Stone, who conducted the research as a Tufts postdoctoral scholar.

“The result that turned our heads was that early life stress reduces the number of dopaminergic neurons between the ventral tegmental area and basolateral amygdala, suggesting that network architecture is impaired.”

To test this hypothesis, Stone and his colleagues leveraged cutting-edge laboratory techniques that allowed them to artificially activate or silence dopamine inputs into the basolateral amygdala from the ventral tegmental area. They applied this to a classic behavioral protocol in which a mouse is given the choice to investigate chambers with either a toy or a stranger mouse.

Mice with carefree early days visited the stranger mouse as expected. However, mice that experienced maternal neglect primarily opted to do nothing or interact with the toy. This was only revealed when the investigators activated the dopaminergic neurons between the ventral tegmental area and basolateral amygdala.

Importantly, when dopaminergic neurons were turned off in animals with carefree early days, they started behaving like animals who grew up with maternal neglect.

“This experiment was a beautiful part to this story that really made me believe in the work,” says Stone. “It’s evidence that social avoidance is governed by a delicate balance of interconnected neural elements and early life stress shapes these connections in a nuanced way that impairs their ability to function.”