Hunger can drive a motivational state that leads to a successful pursuit of a goal, foraging for and finding food.
A study published in Current Biology by researchers at the University of Alabama at Birmingham and the National Institute of Mental Health (NIMH) sheds light on the brain’s role in motivation. The study explored how specific neuronal groups within the thalamus, a brain region called the paraventricular nucleus (PVT), influence goal-oriented behaviors. This research offers valuable insights into how the brain monitors motivational states and guides actions towards achieving desired outcomes.
The Experiment
The study utilized mice trained in a foraging-like task. A long, hallway-like enclosure with a starting zone at one end and a reward zone with a strawberry-flavored Ensure reward over 4 feet away was used. Mice were trained to wait in the starting zone for two seconds until a beep signaled the start of the task. They could then proceed at their own pace to the reward zone to receive the Ensure. Trials ended when the mice left the reward zone and returned to the starting zone to await another signal. Training resulted in proficient and engaged mice, completing numerous trials.
Monitoring Brain Activity
Researchers employed optical photometry and the calcium sensor GCaMP to continuously monitor the activity of two key neuronal subpopulations within the PVT. Monitoring occurred during both phases of the task: reward approach (starting zone to reward zone) and trial termination (reward zone back to starting zone after receiving the reward). This monitoring involved inserting an optical fiber near the PVT to measure calcium release, which signifies neural activity.
Diverse Roles within the Paraventricular Nucleus
The study identified two subpopulations within the paraventricular nucleus (PVT) distinguished by the presence or absence of the dopamine D2 receptor. These subpopulations are referred to as PVTD2(+) and PVTD2(–), respectively. Dopamine acts as a neurotransmitter, facilitating communication between neurons.
The research revealed that PVTD2(+) and PVTD2(–) neurons encode distinct functions: execution and termination of goal-oriented actions, respectively (Beas et al., 2024). Furthermore, activity in the PVTD2(+) population mirrored motivational factors like vigor and satiety.
Detailed Activity Patterns
Specifically, PVTD2(+) neurons exhibited increased activity during reward approach, while decreasing activity during trial termination. Conversely, PVTD2(–) neurons displayed decreased activity during reward approach and increased activity during trial termination.
This discovery highlights the previously unknown diversity within PVT neurons (Beas et al., 2024). For decades, the PVT was considered a homogeneous structure. The study revealed that despite being the same cell type (both releasing glutamate as a neurotransmitter), PVTD2(+) and PVTD2(–) neurons serve distinct purposes. Additionally, these findings offer significant value by aiding in the interpretation of previously contradictory or confusing research regarding PVT function.
From Relay Station to Processing Center
Previously, thalamic regions like the PVT were thought to simply act as relay stations within the brain. Researchers now propose that the PVT plays a more active role in processing information. Beas et al. (2024) suggest the PVT translates need states originating from the hypothalamus into motivational signals. This is achieved through projections of axons, including those from PVTD2(+) and PVTD2(–), to the nucleus accumbens (NAc). The NAc plays a critical role in learning and executing goal-oriented behaviors. An axon is a long, cable-like extension from a neuron that transmits signals to other neurons.
The study employed optical fibers inserted near the NAc, where PVT axon terminals connect with NAc neurons, to monitor changes in neural activity at the PVT. The observed activity dynamics at the PVT-NAc terminals largely mirrored those seen within the PVT neurons themselves: increased activity of PVTD2(+) neurons during reward approach and increased activity of PVTD2(–) neurons during trial termination.
“These findings strongly suggest that motivation-related features and the encoding of goal-oriented actions by posterior PVTD2(+) and PVTD2(–) neurons are relayed to the NAc through their respective terminals.”
Sofia Beas, Ph.D., assistant professor in the UAB Department of Neurobiology
Data Analysis and Motivation Insights
The study generated a substantial dataset due to the high recording frequency (eight to ten samples per second) during each mouse session. Additionally, such recordings are susceptible to various confounding variables.
This necessitated a novel data analysis approach. Researchers employed a robust statistical framework based on Functional Linear Mixed Modeling. This framework addressed recording variability and explored relationships between changes in photometry signals over time and various reward task co-variates. These co-variates included factors like mouse trial speed and hunger levels, which might influence the signal.
For example, researchers categorized trial times into “fast” (two to three seconds) and “slow” (nine to eleven seconds) groups to correlate motivation with task performance.
“The analysis revealed a link between reward approach and higher calcium signal ramps in PVTD2(+) neurons during fast trials compared to slow ones. “Furthermore, a correlation was identified between the signal and both latency (time taken) and velocity parameters. Notably, no changes were observed in PVTD2(+) neuron activity when mice weren’t actively engaged in the task (e.g., roaming the enclosure without performing trials).”
Sofia Beas, Ph.D., assistant professor in the UAB Department of Neurobiology
“Collectively, these findings suggest that PVTD2(+) neuron activity in the posterior region increases during reward-seeking and is influenced by motivation.”
Sofia Beas, Ph.D., assistant professor in the UAB Department of Neurobiology
Potential Applications for Health
Deficits in motivation are linked to psychiatric conditions like substance abuse, binge eating, and anhedonia (inability to experience pleasure) in depression. A deeper understanding of the neural basis of motivation could reveal specific neuronal pathways involved and their interactions. This knowledge might pave the way for new therapeutic targets aimed at restoring healthy motivational processes in patients.
https://doi.org/10.1016/j.cub.2024.02.037
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 PVTD2(+) and PVTD2(−), 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 PVTD2(+) and PVTD2(−) neurons encode the execution and termination of goal-oriented actions, respectively. Furthermore, activity in the PVTD2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVTD2(−) 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.
