Hunger can drive a state of motivation that leads an animal to successfully achieve a goal: seeking and finding food.
In a very novel study published in Current biology, researchers from 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 are involved in the dynamic regulation of goal pursuit. This research provides insights into the mechanisms by which the brain tracks motivational states to shape instrumental actions.
For the study, mice first had to be trained in 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, plus 4 feet away.
The mice learned to wait in a trigger zone for two seconds, until a beep triggered the start of their foraging-like behavioral task. A mouse could then move at its own pace to the reward zone to receive a small drink of strawberry-flavored Ensure. To end the test, the mice had to leave the reward area and return to the activation area, to wait for another beep. The mice learned quickly and became highly engaged, as evidenced by performing a high volume of trials during training.
The researchers then used optical photometry and the calcium sensor GCaMP to continuously monitor the activity of two major neuronal subpopulations of the paraventricular nucleus, or PVT, during reward approach from the trigger zone to the reward zone, and during termination. of the trial from the reward zone. return to the trigger zone after trying a strawberry-flavored food. The experiments involve inserting an optical fiber into the brain, just around the PVT, to measure calcium release, a signal of neuronal activity.
The two subpopulations in the paraventricular nucleus are identified by the presence or absence of the dopamine D2 receptor, called PVT.D2(+) or PVTD2(-), respectively. Dopamine is a neurotransmitter that allows neurons to communicate with each other.
“We found that PVTD2(+) and P.V.T.D2(-) The neurons encode the execution and termination of goal-oriented actions, respectively,” said Sofia Beas, Ph.D., assistant professor in the Department of Neurobiology at UAB and co-corresponding author of the study. “In addition, activity in the PVTD2(+) “The neuronal population reflected motivation parameters such as vigor and satiety.”
Specifically, the PVTD2(+) Neurons showed increased activity during reward approach and decreased activity during trial completion. In contrast, PVTD2(-) Neurons showed decreased activity during reward approach and increased activity during trial completion.
“This is novel because people didn’t know there was diversity within PVT neurons,” Beas said. “Contrary to decades of belief that PVT is homogeneous, we found that although they are the same type of cells (both release the same neurotransmitter, glutamate), PVTD2(+) and P.V.T.D2(-) Neurons do very different jobs. Furthermore, the findings of our study are very significant as they help to interpret contradictory and confusing findings in the literature on PVT function.”
For a long time, thalamic areas like the PVT were considered simply a relay station in the brain. Researchers now realize, Beas says, that the PVT instead processes information, translating hypothalamic-derived need states into motivational signals through projections from axons, including the PVT.D2(+) and P.V.T.D2(-) axons: to the nucleus accumbens or NAc. The NAc plays a fundamental role in learning and executing goal-oriented behaviors. An axon is a long, wire-like extension from the body of a neuronal cell that transfers signal from one neuron to another neuron.
The researchers demonstrated that these changes in neuronal activity in the PVT were transmitted to the NAc by measuring neuronal activity with an optic fiber inserted where the PVT axon terminals reach the NAc neurons. The activity dynamics in the PVT-NAc terminals largely reflected the activity dynamics that the researchers observed in the PVT neurons, that is, an increased signal of PVT neuronal activity.D2(+) during reward approach and increased PVT neural activityD2(-) during the conclusion of the trial.
“Taken together, our findings strongly suggest that motivation-related features and goal-oriented action encoding of later PVTD2(+) and P.V.T.D2(-) “The neurons are transmitted to the NAc through their respective terminals,” Beas said.
During each recording session with the mouse, the researchers recorded eight to ten data samples per second, resulting in a very large data set. Furthermore, these types of recordings are subject to many potential confounding variables. As such, the analysis of these data was another novel aspect of this study, using a new and robust statistical framework based on functional linear mixed modeling that takes into account the variability of the records and can explore the relationships between the changes photometry. signals over time and various covariates of the reward task, such as how quickly the mice performed a trial or how the animals’ hunger levels may influence the signal.
An example of how the researchers correlated motivation with task performance was to separate testing times into “fast” groups, two to three seconds to the reward zone from the trigger zone, and “slow” groups, nine to 11 seconds to the reward zone.
“Our analyzes showed that reward focus was associated with greater calcium signal ramps in PVTD2(+) neurons during fast trials compared to slow ones,” Beas said. “In addition, we found a correlation between the signal and latency and speed parameters. Importantly, there are no changes in the posterior PVT.D2(+) Neural activity was observed when the mice were not engaged in the task, such as in cases where the mice wandered around the enclosure but were not actively testing. Taken together, our findings suggest that posterior PVTD2(+) “Neural activity increases during reward seeking and is determined by motivation.”
Motivation deficits are associated with psychiatric conditions such as substance abuse, binge eating, and the inability to feel pleasure in depression. A deeper understanding of the neural bases of motivated behavior may reveal specific neural pathways involved in motivation and how they interact. This could lead to new therapeutic targets to restore healthy motivational processes in patients.
Co-authors with Beas on the study, “Dissociable coding of motivated behavior by parallel thalamo-striatal projections,” are Isbah Khan, Claire Gao, Gabriel Loewinger, Emma Macdonald, Alison Bashford, Shakira Rodríguez-González, Francisco Pereira and Mario Penzo. NIMH, Bethesda, Maryland. Beas was a postdoctoral fellow at NIMH before moving to UAB last year.
Support came from National Institutes of Health award K99/R00 MH126429, a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation, and NIMH Intramural Research Program award 1ZIAMH002950.