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.

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.

The researchers looked at threatened spring-run Chinook salmon in tributaries of the Sacramento River. It found that restored sites that produce lots of fish may be especially vulnerable to changes such as drought. Such sites should be coupled with other varying sites that support the salmon population in diverse ways.

“The fish need all the different opportunities,” said Flora Cordoleani, a NOAA Fisheries and University of California Santa Cruz researcher who led the research published this week in Ecosphere. “Fish with one life history that favors certain habitat are not going to save the population in the long term. We need diverse habitats to support diverse life histories that help provide resilience.”

Life history refers to salmon traits such as their juvenile migration timing, growth rates, and food preferences. For instance, some juvenile salmon migrate to the ocean in their first year, while others may spend the year growing in freshwater first. That timing may benefit them in some years, but leave them more vulnerable in others, such as during drought.

Spring Chinook salmon were once found across the state and formed the backbone of California’s commercial salmon fishery. They are now greatly diminished and survive in only a few key watersheds with worsening trends in numbers. State and federal biologists last fall collected a few remaining spring-run Chinook salmon to begin a captive broodstock that will safeguard the genetic heritage of the species.

Habitat Mix Benefits Fish

Fish benefit most when they have access to a mosaic of interconnecting habitat from streamside vegetation to open floodplains, the research found. Young salmon may grow rapidly when wet years inundate floodplains and produce plentiful food, “but that happens pretty rarely,” Cordoleani said. “The key is for the fish to have access to all those habitats, so if something happens to one of them, the fish don’t all disappear.”

The new research goes beyond earlier studies showing that later-migrating fish had better survival rates. It shows how that played out on the landscape of three creeks that feed the Sacramento River, one of the biggest salmon-producing rivers on the West Coast.

Cordoleani and her team examined Butte Creek, the focus of extensive restoration that produced a large increase in fish numbers that had access to the floodplain. They examined salmon otoliths — small ear bones — that record clues about each fish’s life history. They found few later-migrating fish, which made the fish there more vulnerable to sharp declines during drought years that may become more common with climate change.

Two other nearby streams, Mill and Deer Creek, offered different conditions and hosted more fish that migrated later as yearlings (juveniles oversummering in freshwater). While they did not see the big increases in fish abundance that Butte Creek did, their salmon better survived droughts. Combining the three sites that complement each other increases the resilience of the Central Valley spring run stock complex — the term for all the individual populations combined.

“The sum of the parts is much greater, because they are doing different things and supporting the fish in different ways,” said Rachel Johnson, the senior author of the research and scientist at NOAA Fisheries’ Southwest Fisheries Science Center. “Some of those qualities may turn out to be more or less important as the climate changes.”

But relying on these three creeks is not enough. “Spring-run Chinook are already playing the climate stock market with only a few stocks in their portfolio,” Johnson said. They were once found in every major watershed. She said a lesson of the research is that more habitat options help fish survive a volatile climate by providing more opportunities to survive and thrive.

Providing that array of options requires restoring diverse habitat areas that complement each other at the landscape scale and returning salmon to historical habitats that had long vanished. Cordoleani and her team hope that this research encourages restoration planners to implement projects that create a mosaic of different habitats across watersheds that support diverse fish survival strategies. These actions will also balance each other to help stabilize numbers in the long term.

The study was published today in Circulation Research, an official journal of the American Heart Association.

“The impact of circadian rhythms on cardiovascular function and disease development is well established,” said the study’s lead author Tobias Eckle, MD, PhD, professor of anesthesiology at the University of Colorado School of Medicine. “However, translational preclinical studies targeting the heart’s circadian biology are just now emerging and are leading to the development of a novel field of medicine termed circadian medicine.”

The senior author is Professor Tami A. Martino, PhD, distinguished chair in molecular and cardiovascular research at the University of Guelph in Ontario, Canada.

The study reviews current circadian medicine research, focusing on the use of intense light therapy following surgery, utilizing light to treat cardiac injury, exploring how cardiovascular disease can differ between men and women and administering drugs at specific times of day to coincide with the body’s internal clock to speed healing.

It also urges more aggressive use of this therapy in humans, rather than relying on mostly animal models.

“There are literally millions of patients who could benefit from this,” Eckle said. “The treatments are almost all low-risk. Some involve using light boxes and others use drugs that are already on the market.”

Circadian rhythms significantly influence how the cardiovascular system operates. Timing is everything. Blood pressure and heart rates follow distinct patterns, peaking during the day and ebbing at night. When this is disrupted, it leads to worse cardiovascular disease outcomes including myocardial infarction and heart failure.

Light is critical in maintaining the proper balance and functioning of the body. Shift employees who may work night hours then day hours often have worse cardiac outcomes.

Eckle, who has studied circadian rhythm and health for years, said intense light can help heal the body after heart surgery while protecting it from injury during surgery, including reducing the chances of cardiac ischemia.

According to the researchers, when light hits the human eye it is transmitted to the suprachiasmatic nucleus, a structure in the brain’s hypothalamus that regulates most circadian rhythms in the body. Intense light stabilizes the PER2 gene and increases levels of adenosine, which blocks electrical signals in the heart that cause irregular rhythms, making it cardiac protective.

Eckle has used light therapy with patients after surgery and seen positive results including lower levels of troponin, a key protein whose elevation can signal a heart attack or stroke.

Given the mounting evidence that intense light and timed drug treatments are effective, he said, it is time to move forward with more clinical trials.

“Circadian rhythms play a crucial role in cardiovascular health, influencing the timing of onset and severity of cardiovascular events and contributing to the healing process from disease,” Eckle said. “Studies in humans are clearly required. Regarding intense light therapy, chronotherapy and restricted feeding are low-risk strategies that should be tested sooner than later.”

“Much of the physics of the known universe already have fundamental solutions or are too complex to get an exact answer,” said Willie Padilla, professor of electrical and computer engineering at Duke. “In any field, finding a truly novel, fundamental, exact result like this is rare.”

The research appeared online March 8in the journal Nanophotonics.

Whether building an antenna or developing sunscreen, there are many instances where certain types of light need to be absorbed. One trick to maximizing that amount is increasing the thickness of the material absorbing the energy.

However, the needed thickness for a transparent material to provide that absorption was unknown till now.

More than 20 years ago, Konstantin N. Rozanov of the Institute for Theoretical and Applied Electrodynamics in Moscow, Russia, figured out the most light over a range of wavelengths that a device of a certain thickness could absorb if one side was lined with metal. This scenario creates a boundary on one side where all light either reflects back or is absorbed, providing a constraint that allows a certain mathematical approach to crack the problem.

Taking away that metal edge and allowing the light to continue through, however, is a horse of an entirely different color on the electromagnetic spectrum.

“Rozanov used a clever trick where he worked in wavelength instead of frequency,” said Yang Deng, a research assistant working in Padilla’s laboratory. “But several researchers have since tried using that approach to this problem and failed.”

To come up with a new mathematical approach, Padilla and Deng collaborated with Vahid Tarokh, the Rhodes Family Professor of Electrical and Computer Engineering at Duke. Tarokh’s research spans a wide range of topics while pursuing new formulations and approaches to getting the most out of datasets.

Without getting too deep into the mathematical weeds, it can be said that Tarokh was able to figure out how to shape the problem so that it could be solved, pulling a rabbit from a mathematical hat.

“Hindsight is 20/20, but even mathematicians call these creative strategies ‘tricks,'” Padilla said.

Beyond the novelty of solving a long-sought-after problem, the researchers say their work has practical implications in several areas. Metal-backed absorbers won’t let any type of electromagnetic energy pass through. But there are certain applications where you might want to block some frequencies while letting others pass.

For example, cellular phones might want to be able to block certain types of harmful electromagnetic radiation while letting others like GPS or Bluetooth through. Knowing what the fundamental limits of this type of goal will allow engineers to know when more work optimizing their design will not be worth the effort.

This research was supported by the Department of Energy (DESC0014372).