Brain’s Motivation Mechanics: How Hunger Drives Goal Pursuit

Summary: Researchers unveiled how the brain’s thalamus navigates hunger-driven motivation. Through innovative experiments with mice, the study explores the role of two distinct neuronal populations within the paraventricular nucleus (PVT), showing how they regulate actions towards achieving a goal, like foraging for food.

The study demonstrates that dopamine D2 receptor-positive (PVTD2(+)) neurons amplify motivation and pursuit behaviors, while their counterparts, PVTD2(–) neurons, are associated with action termination. This discovery challenges previous notions of the PVT’s uniformity, suggesting its critical role in translating hunger into motivated action, which could lead to new treatments for motivation-related psychiatric conditions.

Key Facts:

1. Distinct Neuronal Roles: PVTD2(+) neurons increase activity during goal pursuit, reflecting heightened motivation, while PVTD2(–) neurons are more active during action termination, balancing the pursuit.
2. Reevaluation of the PVT: Contrary to the traditional view of the PVT as a mere relay station, this study highlights its complex role in processing motivational signals and influencing goal-oriented behaviors.
3. Potential Therapeutic Targets: Understanding the PVT’s dual functions opens new avenues for addressing motivational deficits in psychiatric conditions, offering hope for targeted therapies.

Source: University of Alabama at Birmingham

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.”

For a long time, the thalamic areas such as the PVT had been considered just a relay station in the brain. Researchers now realize, Beas says, that the PVT instead processes information, translating hypothalamic-derived needs states into motivational signals via projections of axons — including the PVT^D2(+) and PVT^D2(–) axons — to the nucleus accumbens, or NAc.

The NAc has a critical role in the learning and execution of goal-oriented behaviors. An axon is a long cable-like extension from a neuron cell body that transfers the neuron’s signal to another neuron.

Researchers showed that these changes in neuron activity at the PVT were transmitted to the NAc by measuring neural activity with an optical fiber inserted where the terminals of the PVT axons reach the NAc neurons.

The activity dynamics at the PVT-NAc terminals largely mirrored the activity dynamics the researchers saw at the PVT neurons — namely increased neuron activity signal of PVT^D2(+) during reward approach and increased neuron activity of PVT^D2(–) during trial termination.

“Collectively, our findings strongly suggest that motivation-related features and the encoding of goal-oriented actions of posterior PVT^D2(+) and PVT^D2(-) neurons are being relayed to the NAc through their respective terminals,” Beas said.

During each mouse recording session, the researchers recorded eight to 10 data samples per second, resulting in a very big dataset. In addition, these types of recordings are subject to many potential confounding variables.

As such, the analysis of this data was another novel aspect of this study, through use of a new and robust statistical framework based on Functional Linear Mixed Modeling that both account for the variability of the recordings and can explore the relationships between the changes of photometry signals over time and various co-variates of the reward task, such as how quickly mice performed a trial, or how the hunger levels of the animals can influence the signal.

One example of how researchers correlated motivation with task performance was separating the trial 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 analyses showed that reward approach was associated with higher calcium signal ramps in PVT^D2(+) neurons during fast compared to slow trials,” Beas said.

“Moreover, we found a correlation between signal and both latency and velocity parameters. Importantly, no changes in posterior PVT^D2(+) neuron activity were observed when mice were not engaged in the task, as in the cases where mice were roaming around the enclosure but not actively performing trials.

“Altogether, our findings suggest that posterior PVT^D2(+) neuron activity increases during reward-seeking and is shaped by motivation.”

Deficits in motivation are associated with psychiatric conditions like substance abuse, binge eating and the inability to feel pleasure in depression. A deeper understanding of the neural basis of motivated behavior may reveal specific neuronal 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 in the study, “Dissociable encoding of motivated behavior by parallel thalamo-striatal projections,” are Isbah Khan, Claire Gao, Gabriel Loewinger, Emma Macdonald, Alison Bashford, Shakira Rodriguez-Gonzalez, Francisco Pereira and Mario Penzo, NIMH, Bethesda, Maryland. Beas was a post-doctoral fellow at the NIMH before moving to UAB last year.

Funding: Support came from National Institutes of Health award K99/R00 MH126429, a NARSAD Young Investigator Award by the Brain and Behavior Research Foundation, and NIMH Intramural Research Program award 1ZIAMH002950.

About this hunger and motivation research news

Author: Jeffrey Hansen
Source: University of Alabama at Birmingham
Contact: Jeffrey Hansen – University of Alabama at Birmingham
Image: The image is credited to Neuroscience News

Original Research: Open access.
“Dissociable encoding of motivated behavior by parallel thalamo-striatal projections” by Sofia Beas et al. Current Biology

Abstract

Dissociable encoding of motivated behavior by parallel thalamo-striatal projections

Highlights

• PVT^D2(+)-NAc pathway encodes the execution of goal-oriented actions
• PVT^D2(−)-NAc pathway encodes the termination of goal-oriented actions
• The activity of PVT^D2(+) neurons correlated with motivation parameters
• PVT^D2(−) neuronal activity correlated with motivation, but to a lesser degree

Summary

The successful pursuit of goals requires the coordinated execution and termination of actions that lead to positive outcomes. This process relies on motivational states that are guided by internal drivers, such as hunger or fear. However, the mechanisms by which the brain tracks motivational states to shape instrumental actions are not fully understood.

The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that shapes motivated behaviors via its projections to the nucleus accumbens (NAc) and monitors internal state via interoceptive inputs from the hypothalamus and brainstem.

Recent studies indicate that the PVT can be subdivided into two major neuronal subpopulations, namely PVT^D2(+) and PVT^D2(−), which differ in genetic identity, functionality, and anatomical connectivity to other brain regions, including the NAc.

In this study, we used fiber photometry to investigate the in vivo dynamics of these two distinct PVT neuronal types in mice performing a foraging-like behavioral task. We discovered that PVT^D2(+) and PVT^D2(−) neurons encode the execution and termination of goal-oriented actions, respectively.

Furthermore, activity in the PVT^D2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVT^D2(−) neurons also mirrored some of these parameters, but to a much lesser extent. Importantly, these features were largely preserved when activity in PVT projections to the NAc was selectively assessed.

Collectively, our results highlight the existence of two parallel thalamo-striatal projections that participate in the dynamic regulation of goal pursuits and provide insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.