Brain cells work in tandem to regulate goal-oriented behavior in mice

Hunger can drive a motivational state that leads an animal to a successful pursuit of a goal—foraging for and finding food.

In a highly novel study published in Current Biology, researchers at the University of Alabama at Birmingham and the National Institute of Mental Health, or NIMH, describe how two major neuronal subpopulations in a part of the brain's thalamus called the paraventricular nucleus participate in the dynamic regulation of goal pursuits. This research provides insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.

For the study, mice first had to be trained in a foraging-like behavior, using a long, hallway-like enclosure that had a trigger zone at one end and a reward zone at the other end, more than 4 feet distant.

Mice learned to wait in a trigger zone for two seconds, until a beep triggered initiation of their foraging-like behavioral task. A mouse could then move forward at its own pace to the reward zone to receive a small gulp of strawberry-flavored Ensure. To terminate the trial, the mice needed to leave the reward zone and return to the trigger area, to wait for another beep. Mice learned quickly and were highly engaged, as shown by completing a large volume of trials during training.

The researchers then used optical photometry and the calcium sensor GCaMP to continuously monitor activity of two major neuronal subpopulations of the paraventricular nucleus, or PVT, during the reward approach from the trigger zone to the reward zone, and during the trial termination from the reward zone back to the trigger zone after a taste of strawberry-flavored food. The experiments involve inserting an optical fiber into the brain just about the PVT to measure calcium release, a signal of neural activity.

The two subpopulations in the paraventricular nucleus are identified by presence or absence of the dopamine D2 receptor, noted as either PVT^D2(+) or PVT^D2(–), respectively. Dopamine is a neurotransmitter that allows neurons to communicate with each other.

“We discovered that PVT^D2(+) and PVT^D2(–) neurons encode the execution and termination of goal-oriented actions, respectively,” said Sofia Beas, Ph.D., assistant professor in the UAB Department of Neurobiology and a co-corresponding author of the study. “Furthermore, activity in the PVT^D2(+) neuronal population mirrored motivation parameters such as vigor and satiety.”

Specifically, the PVT^D2(+) neurons showed increased activity during the reward approach and decreased activity during trial termination. Conversely, PVT^D2(–) neurons showed decreased activity during the reward approach and increased activity during trial termination.

“This is novel because people didn't know there was diversity within the PVT neurons,” Beas said. “Contrary to decades of belief that the PVT is homogeneous, we found that, even though they are the same types of cells (both release the same neurotransmitter, glutamate), PVT^D2(+) and PVT^D2(–) neurons are doing very different jobs. Additionally, the findings from our study are highly significant as they help interpret contradictory and confusing findings in the literature regarding PVT's function.”

Source: University of Alabama at Birmingham