Do Monte research on recollection of environmental cues published in eLife

By Roman Petrowski, Office of Communications

Dr. Fabricio Do Monte - Recollection of behavioral cues paper
Fabricio Do Monte, DVM, PhD

Recent research from the lab of Fabricio Do Monte, DVM, PhD, assistant professor in the Department of Neurobiology and Anatomy, on the behavioral responses of animals based on the recollection of environmental cues has been published in the journal eLife.

Co-first authors in the paper titled Neural correlates and determinants of approach-avoidance conflict in the prelimbic prefrontal cortex are the former postdoctoral fellow Jose Fernandez-León, PhD, and postdoctoral fellows Douglas Engelke, PhD, and Guillermo-Aquino Miranda, PhD.

“The brain’s ability to identify and discriminate cues associated with threat or reward allows organisms to respond appropriately to changes in the environment,” Fernandez-León explained. “Animals respond to threatening cues with a series of defensive behaviors including avoidance responses that decrease their chances of being exposed to aversive outcomes. In contrast, reward cues have attractive and motivational properties that elicit approach behavior.”

Though the behavioral responses to both reward- and threat-associated cues are well researched, the Do Monte Lab sought to determine if the prelimbic (PL) subregion of the prefrontal cortex regulates threat-avoidance and reward-approaching responses when individuals have to remember previously associated memories to make decisions.

“While many studies have investigated the neural mechanisms that control threat-avoidance and reward-approach independently of each other, it is unclear how the brain uses previously learned information to regulate the opposing behavioral drives of avoiding threats and seeking rewards during a conflict situation,” Engelke said.

According to the authors, previous research has shown that neurons in the PL change their firing rates in response to cues that predict threats or rewards, and such activity in PL neurons is necessary for the retrieval of both food- and threat-associated memories.

The lab designed an approach-avoidance conflict paradigm to investigate the ability of preclinical models to remember cues previously associated with rewards (positive valence) or threats (negative valence). Next, subjects were exposed to both positive and negative cues combined to create a motivational conflict that allowed the authors to investigate individual differences in risk-taking behavior. From there, the lab recorded the variability in reward seeking and defensive responses during the test and correlated those behaviors with the firing rate of photoidentified glutamatergic and GABAergic neurons in the PL.

During the approach-avoidance conflict test, the lab identified two behavioral phenotypes during the presentation of both reward- and threat-paired cues. Subjects either continued to press a lever for food (Pressers) or they completely stopped food-seeking responses (Non-pressers). Through single-unit recordings, the authors also revealed that when the subjects used previously associated memories to guide their decisions, activity in PL neurons regulate the reward-approach vs. threat-avoidance responses.

“We observed that increased risk-taking behavior in Pressers was associated with a larger number of food-cue responsive neurons in PL, which showed sustained excitatory activity that persisted during the conflict phase, when compared to Non-pressers,” Aquino-Miranda explained.

Additionally, the lab used an optogenetic approach to selectively activate PL glutamatergic (PLGLUT) and PL GABAergic (PLGABA) neurons to further determine whether changes in the activity of these cells can alter behavioral responses. These experiments showed that increasing the activity of PLGLUT neurons (but not PLGABA neurons) suppresses cued reward-seeking responses in Pressers, whereas inactivating PLGLUT neurons in Non-Pressers reduced defensive responses and increased food approaching during conflict.

“Overall, our results outline the neural correlates of risk-taking and risk-avoiding behaviors in PL and reveal an important role for PLGLUT neurons in coordinating memory-based risky decision making during conflict situations,” the authors said.

Moving forward, the lab will focus on identifying the PL circuits responsible for the regulation of reward-approaching and threat-avoidance responses, and what potential factors could contribute to the observed behavioral phenotypes.

“Elucidating the underlying mechanisms that mediate risk-taking versus risk-avoiding responses during situations of uncertainty may help to provide understanding of response selection and adaptive behaviors, and may have clinical relevance to many psychiatric disorders,” Do Monte concluded.

Other contributing authors to the article are Maria N. Rasheed, former research assistant, and Alexandria Goodson, former undergraduate student in Do Monte’s lab. This work was supported by a National Institutes of Health (NIH) grant R00-MH105549, an NIH grant R01-MH120136, a Brain & Behavior Research Foundation grant (NARSAD Young Investigator), and a Rising STARs Award from UT System to Do Monte.