Research provides insight into how the brain translates motivation into goal-directed behavior

Hunger can induce a motivational state that leads animals to achieve their goals. To search for or find food.

In a very innovative study published in current biology, researchers at the University of Alabama at Birmingham and the National Institute of Mental Health (NIMH) found that two major subpopulations of neurons in a part of the brain's thalamus called the paraventricular nucleus play a role in the dynamic regulation of goal pursuit. It explains how it is involved. This study provides insight into the mechanisms by which the brain tracks motivational states and shapes instrumental behavior.

The study required first training mice to perform foraging-like behaviors using a long hallway-like enclosure with a trigger zone at one end and a reward zone at the other, spaced at least 4 feet apart. had.

Mice learned to wait 2 seconds in the trigger zone until a beep initiated a behavioral task such as foraging. The mouse then proceeds to the reward zone at its own pace and takes a small sip of the strawberry-flavored Ensure. To end the trial, the mouse had to exit the reward zone, return to the trigger area, and wait for another beep. The mice were fast learners and engaged, as evidenced by the large number of trials they completed during training.

The researchers then used photophotometry and the calcium sensor GCaMP to detect two major areas in the paraventricular nucleus (PVT) during reward approach from the trigger zone to the reward zone and during trial exit from the reward zone. We continuously monitored the activity of neuronal subpopulations. After tasting strawberry-flavored food, you return to the trigger zone. The experiment involves inserting an optical fiber into the brain near her PVT to measure calcium release, a signal of neural activity.

Two subpopulations within the paraventricular nucleus are distinguished by the presence or absence of dopamine D2 receptors and are designated as PVT.^D2(+) or PVT^D2(-), Each. Dopamine is a neurotransmitter that allows neurons to communicate with each other.

Found PVT^D2(+) and P.V.T.^D2(-) Each neuron encodes the execution and termination of a goal-directed action.In addition, activities at PVT^D2(+) Neuronal populations reflected motivational parameters such as vitality and satiety. ”

Dr. Sophia Bies, assistant professor in the UAB Department of Neurobiology and co-corresponding author of the study

Specifically, P.V.T.^D2(+) Neurons showed increased activity during reward approach and decreased activity during trial termination. Conversely, PVT^D2(-) Neurons showed decreased activity during reward approach and increased activity during trial termination.

“This is novel because people didn't know there was diversity within PVT neurons,” Bees said. “Contrary to the decades-old belief that the PVT is homogeneous, even though the PVT is the same type of cell (both release the same neurotransmitter, glutamate), the PVT^D2(+) and P.V.T.^D2(-) Neurons have a completely different job. Moreover, the findings of our study are of great importance as they help interpret the contradictory and confusing findings in the literature regarding the function of PVT. ”

For a long time, thalamic regions such as the PVT were thought to be little more than relay stations in the brain. Bees says researchers now realize that the PVT processes information instead, converting hypothalamic-derived need states into motivational signals via axonal projections. Including PVT^D2(+) and P.V.T.^D2(-) Axons -; to the nucleus accumbens, or NAc. The NAc plays an important role in the learning and execution of goal-directed behaviors. An axon is a long cable-like extension from a neuron's cell body that transmits a neuron's signals to another neuron.

The researchers showed that these changes in neuronal activity in the PVT are transmitted to the NAc by measuring neural activity with optical fibers inserted where the ends of PVT axons reach NAc neurons. . The dynamics of activity in the PVT-NAc terminals roughly mirrored the dynamics of activity that the researchers observed in his PVT neurons.i.e., increased neuronal activity signals in the PVT.^D2(+) During reward approach and increased neuronal activity in the PVT^D2(-) Trial is ending.

“Taken together, our findings strongly suggest motivation-related features and encoding of goal-directed behavior in the posterior PVT.^D2(+) and P.V.T.^D2(-) Neurons are relayed to the NAc through their respective terminals,” Beas said.

During each mouse recording session, the researchers recorded 8 to 10 data samples per second, resulting in a very large dataset. Additionally, this type of recording is subject to many potential confounding variables. The analysis of this data is therefore another novel part of this study, through the use of a new and robust statistical framework based on functional linear mixed modeling that allows for the variability of recordings and the investigation of relationships between changes in photometry. It was the side. Analyze the signal over time and various covariates of the reward task, such as the speed at which the mouse performs trials and how the animal's hunger level affects the signal.

As an example of how researchers correlated motivation and task performance, a “fast” group with trial times of 2 to 3 seconds from trigger zone to reward zone and a “slow” group with trial times of 9 to 11 seconds from reward zone. Divided into.

“Our analysis showed that reward approaches are associated with increased calcium signals in the PVT.^D2(+) “We observed an increase in neurons during fast trials compared to slow trials,” Beas said. “Additionally, we found a correlation between the signal and both latency and speed parameters.” Importantly, there was no change in rear PVT.^D2(+) Neuronal activity was observed when the mice were not participating in the task, such as when they were walking around the enclosure but not actively performing trials.In summary, our findings indicate that posterior PVT^D2(+) Neuron activity increases when seeking rewards and is shaped by motivation. ”

Lack of motivation is associated with mental illnesses such as substance abuse, bulimia, and depression that prevents people from experiencing pleasure. A deeper understanding of the neural basis of motivated behavior may reveal the specific neural pathways involved in motivation and how they interact. This may lead to new therapeutic targets for restoring healthy motivational processes in patients.

Beas' co-authors on the study, “Dissociative encoding of motivated behavior by parallel thalamo-striatal projections,” are Isbah Khan, Claire Gao, Gabriel Loewinger, Emma Macdonald, Alison Bashford, Shakira Rodriguez-Gonzalez, and Francisco Pereira. , Mario Penzo. NIMH, Bethesda, Maryland. Bees was a postdoctoral fellow at NIMH before moving to UAB last year.

Support was provided by National Institutes of Health Award K99/R00 MH126429, NARSAD Young Investigator Award from the Brain and Behavioral Research Foundation, and NIMH Intramural Research Program Award 1ZIAMH002950.

At UAB, neurobiology is a division of the Marnix E. Hersink School of Medicine.