Pursuit of reward and avoidance of threat are two major behavioral motivators. Failure to balance these motivations results in maladaptive decisions and may underlie various pathological conditions. The sustained threat construct of the NIMH Research Domain Criteria (RDoC) includes avoidance, conflict detection, and perseverative behaviors. Sustained threat reactions interfere with the pursuit of rewarding activities that can decrease social interactions and trigger depression. Little is known about how decisions guide behavior during approach-avoidance conflict. The first phase of this MERIT shifted our focus from Pavlovian fear conditioning to active avoidance, exploring how prefrontal-amygdala-striatal circuits express and extinguish active avoidance. For the second MERIT phase, we have developed a new task that maximizes approach-avoidance conflict within a timed cue encounter that pits active avoidance against the pursuit of food. The new approach-avoidance conflict task has revealed three distinct behavioral phenotypes: 1) food-preferring rats that pursue food throughout the tone with little or no avoidance; 2) avoidance-preferring rats which avoid throughout the tone with little or no food-seeking; and 3) timers which seek food early in the tone and avoid later, thereby maximizing both access to food and safety. We will capitalize on these unique behavioral phenotypes to characterize the circuits mediating approach- avoidance decisions, using electrophysiological, immunohistochemical, and optogenetic methods. We will use both male and female rats in all our aims.
Aim 1 will use immunohistochemistry combined with electrophysiology and fiber photometry to identify the circuits involved in conflict decision making.
Aim 2 will test the circuits identified in Aim 1 with optogenetic manipulations.
Aim 3 will assess the power of this task to identify new multi-dimensional behavioral phenotypes integrating conflict strategies with anxiety and social interactions. This research program will enable us to characterize decision-making circuits underlying different strategies for resolving approach-avoidance conflict.

Public Health Relevance

Failure to balance pursuit of reward and avoidance of threat results in maladaptive decisions and pathological conditions including anxiety and depression. Using a novel rodent task that maximizes approach-avoidance conflict, we will characterize the circuits mediating approach-avoidance decisions using electrophysiological, immunohistochemical, and optogenetic methods. This research program will enable us to characterize circuits for resolving approach-avoidance conflict.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37MH058883-24
Application #
9918979
Study Section
Special Emphasis Panel (NSS)
Program Officer
Vicentic, Aleksandra
Project Start
2018-08-01
Project End
2023-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
24
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of Puerto Rico Med Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
948108063
City
San Juan
State
PR
Country
United States
Zip Code
00936
Rosas-Vidal, Luis E; Lozada-Miranda, Valeria; Cantres-Rosario, Yisel et al. (2018) Alteration of BDNF in the medial prefrontal cortex and the ventral hippocampus impairs extinction of avoidance. Neuropsychopharmacology 43:2636-2644
Diehl, Maria M; Bravo-Rivera, Christian; Rodriguez-Romaguera, Jose et al. (2018) Active avoidance requires inhibitory signaling in the rodent prelimbic prefrontal cortex. Elife 7:
Do-Monte, Fabricio H; Minier-Toribio, Angélica; Quiñones-Laracuente, Kelvin et al. (2017) Thalamic Regulation of Sucrose Seeking during Unexpected Reward Omission. Neuron 94:388-400.e4
Quirk, Gregory J (2017) Less fear, more diversity. PLoS Biol 15:e2002079
Paré, Denis; Quirk, Gregory J (2017) WHEN SCIENTIFIC PARADIGMS LEAD TO TUNNEL VISION: LESSONS FROM THE STUDY OF FEAR. NPJ Sci Learn 2:
Rodriguez-Romaguera, Jose; Greenberg, Benjamin D; Rasmussen, Steven A et al. (2016) An Avoidance-Based Rodent Model of Exposure With Response Prevention Therapy for Obsessive-Compulsive Disorder. Biol Psychiatry 80:534-40
Do Monte, F H; Quirk, G J; Li, B et al. (2016) Retrieving fear memories, as time goes by…. Mol Psychiatry 21:1027-36
Heilbronner, Sarah R; Rodriguez-Romaguera, Jose; Quirk, Gregory J et al. (2016) Circuit-Based Corticostriatal Homologies Between Rat and Primate. Biol Psychiatry 80:509-21
Bravo-Rivera, Christian; Roman-Ortiz, Ciorana; Montesinos-Cartagena, Marlian et al. (2015) Persistent active avoidance correlates with activity in prelimbic cortex and ventral striatum. Front Behav Neurosci 9:184
Do-Monte, Fabricio H; Manzano-Nieves, Gabriela; Quiñones-Laracuente, Kelvin et al. (2015) Revisiting the role of infralimbic cortex in fear extinction with optogenetics. J Neurosci 35:3607-15

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