How brain decides 'should I stay or should I go?'

Our everyday decisions about whether to "stay" or to "go" are supported by a brain region called the anterior cingulate cortex (ACC), which is part of the prefrontal cortex.

Neuroscientists from Cold Spring Harbor Laboratory (CSHL) have now identified key circuit elements that contribute to such decisions in the ACC.

CSHL Associate Professor Adam Kepecs and his team have linked specific brain cell types to a particular behavior pattern in mice - a "stay or go" pattern called foraging behavior.

The results showed that the firing of two distinct types of inhibitory neurons, known as somatostatin (SOM) and parvalbumin (PV) neurons, has a strong correlation with the start and end of a period of foraging behavior.

Key to solving that problem is a mouse model developed in the laboratory of CSHL Professor Z. Josh Huang. The mouse has a genetic modification that allows investigators to target a specific population of neurons with any protein of interest.

Kepecs' group, led by postdocs Duda Kvitsiani and Sachin Ranade, used this mouse to label specific neuron types in the ACC with a light-activated protein - a technique known as optogenetic tagging. Whenever they shone light onto the brains of the mice they were recording from, only the tagged PV and SOM neurons responded promptly with a 'spike' in their activity, enabling the researchers to pick them out from the vast diversity of cellular responses seen at any given moment.

The team recorded neural activity in the ACC of these mice while they engaged in foraging behavior. They discovered that the PV and SOM inhibitory neurons responded around the time of the foraging decisions-in other words whether to stay and drink or go and explore elsewhere.

Specifically, when the mice entered an area where they could collect a water reward, SOM inhibitory neurons shut down and entered a period of low-level activity, thereby opening a 'gate' for information to flow in to ACC. When the mice decided to leave that area and look elsewhere, PV inhibitory neurons fired and abruptly reset cell activity.

This is an important advance, addressing a problem in behavioral neuroscience that scientists call "the cortical response zoo." When researchers record neural activity in cortex during behavior, and they don't know which type of neurons they are recording from, a bewildering array of responses is seen. This greatly complicates the task of interpretation.

Hence the significance of the Kepecs team's results, for the first time showing that specific cortical neuron types can be linked to specific aspects of behavior.

"We think about the brain and behavior in terms of levels; what the cell types are and the circuits or networks they form; which regions of the brain they are in; and what behavior is modulated by them," explained Kepecs.

"By observing that the activity of specific cell types in the prefrontal cortex is correlated with a behavioral period, we have identified a link between these levels," he added.

The research was published online in Nature.