Daily decisions such as getting up off the couch to go for a snack or remaining and surfing channels may be influenced by which type of nerve cell is activated in the brain.
Neuroscientists from Cold Spring Harbor Laboratory (CSHL) have now identified key circuit elements that contribute to such decisions in the anterior cingulate cortex (ACC), part of the prefrontal cortex.
In a study published in Nature, Adam Kepecs, Ph.D., and his team discovered, for the first time, specific brain cell types to a particular behavior pattern in mice – a “stay or go” pattern called foraging behavior.
The paper shows 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.
Linking specific neuronal types to well-defined behaviors has proved extremely difficult.
“There’s a big gap in our knowledge between our understanding of neuron types in terms of their physical location and their place in any given neural circuit, and what these neurons actually do during behavior,” Kepecs said.
Part of the problem is the technical challenge of doing these studies in live, freely behaving mice.
Key to solving that problem is a mouse model developed in the laboratory of Cold Spring Harbor Laboratory, in which 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 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 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.
“The brain is complex and continuously active, so it makes sense that these two types of inhibitory interneurons define the boundaries of a behavior such as foraging, opening and then closing the ‘gate’ within a particular neural circuit through changes in their activity,” said Kepecs.
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,” Kepecs said.
“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.”
Source: Cold Spring Harbor Laboratory