A hypothalamic-thalamostriatal circuit that controls approach-avoidance conflict in rats

Abstract

Survival depends on a balance between seeking rewards and avoiding potential threats, but the neural circuits that regulate this motivational conflict remain largely unknown. Using an approach-food vs. avoid-predator threat conflict test in rats, we identified a subpopulation of neurons in the anterior portion of the paraventricular thalamic nucleus (aPVT) which express corticotrophin-releasing factor (CRF) and are preferentially recruited during conflict. Inactivation of aPVTCRF neurons during conflict biases animal’s response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVTCRF neurons project densely to the nucleus accumbens (NAc), and activity in this pathway reduces food seeking and increases avoidance. In addition, we identified the ventromedial hypothalamus (VMH) as a critical input to aPVTCRF neurons, and demonstrated that VMH-aPVT neurons mediate defensive behaviors exclusively during conflict. Together, our findings describe a hypothalamic-thalamostriatal circuit that suppresses reward-seeking behavior under the competing demands of avoiding threats.

Extinction blunts paraventricular thalamic contributions to heroin relapse

“…Based on emerging evidence in recent years, the PVT has been conceptualized to act as an emotional and motivational hub ( Choi et al, 2019 ; Choi and McNally, 2017 ; Hsu et al, 2014 ; Kirouac, 2015 ). The PVT contributes to conditioned fear ( Do-Monte et al, 2015 ; Penzo et al, 2015 ), conditioned sucrose ( Do-Monte et al, 2017 ; Labouèbe et al, 2016 ; Livneh et al, 2017 ), appetitive learning ( Otis et al, 2017 ), as well as drug seeking ( Giannotti et al, 2018 ; Hamlin et al, 2009 ; James et al, 2010 ; Kuhn et al, 2018 ; Matzeu and Martin-Fardon, 2018 ; Zhou et al, 2021 ) and food seeking ( Christoffel et al, 2021 ; Engelke et al, 2021 ), depending on specific PVT inputs and outputs ( Millan et al, 2017 ; Penzo and Gao, 2021 ). Moreover, PVT neurons encode multiple salient features of sensory stimuli, including aversive valence ( Li et al, 2011 ; Yasoshima et al, 2007 ; Zhu et al, 2018 ).…”

The Paraventricular Thalamus as a Critical Node of Motivated Behavior via the Hypothalamic-Thalamic-Striatal Circuit

“…Inactivation of these neurons biases an animal's response toward food, whereas activation enables suppression of food-seeking behavior during conflict. Further, it was determined that input from the ventromedial hypothalamus to aPVT CRF neurons, and output from aPVT CRF neurons to the NAc, are critical components of the circuit that modulates reward-seeking behavior under competing demands of avoiding threats (Engelke et al, 2021). These studies collectively support a role for the PVT as an arbitrator that encodes the value of external stimuli and internal states and, in turn, facilitates adaptive behavior.…”

“…Specifically, chemogenetic inhibition across the anterior-posterior axis of the PVT disrupts cue-elicited appetitive behavior and increases cue-elicited aversive behavior under conditions of motivational conflict (Choi et al, 2019). More recently, it was shown that a subpopulation of neurons in the aPVT that express corticotropin-releasing factor (CRF) is particularly important for regulating responses during motivational conflict (Engelke et al, 2021). Inactivation of these neurons biases an animal's response toward food, whereas activation enables suppression of food-seeking behavior during conflict.…”

Thalamo-Nucleus Accumbens Projections in Motivated Behaviors and Addiction

“…Interestingly, in an operant chamber, acute PVT = > NAc stimulation contingent to lever press induced self-stimulation, suggesting that brief synchronous activation of these projections is reinforcing rather than aversive (Lafferty et al, 2020). Finally, a recent study showed that the precise stimulation of aPVT neurons expressing corticotrophin-releasing factor (aPVT CRF ) and projecting to the NAc shell induced behavioral aversion in the RTPP (Engelke et al, 2021).…”

“…Another study showed that the activation of aPVT = > NAc neurons increased feeding behavior in a novel environment, without altering anxiety behaviors (Cheng et al, 2018). Recently, aPVT CRF = > NAc has also been shown to control the conflict between approach-food and avoid-predator threat by suppressing food-seeking in the presence of a predator odor (Engelke et al, 2021). It is likely that the PVT = > NAc modulation during conflict also strongly depends on the internal state of the animal as well as on the precise experimental conditions, possibly explaining (in addition to the precise cellular identity of the neurons targeted in the aPVT) the discrepancies between these last two studies.…”