4.8 Article

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

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NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -

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NATURE RESEARCH
DOI: 10.1038/s41467-021-22730-y

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资金

  1. CIHR [MOP-89758]
  2. NIH [R00-MH105549, R01-MH120136]
  3. Brain & Behavior Research Foundation
  4. Rising STARs Award from UT System

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The study reveals that specific CRF-positive neurons in the paraventricular thalamus of rats are crucial in mediating defensive behaviors during conflicts between seeking rewards and avoiding threats. These neurons project to the nucleus accumbens, impacting food seeking and avoidance behaviors. Furthermore, the interaction between the ventromedial hypothalamus and aPVT neurons plays a key role in the modulation of defensive responses during conflicts.
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 aPVT(CRF) neurons during conflict biases animal's response toward food, whereas activation of these cells recapitulates the food-seeking suppression observed during conflict. aPVT(CRF) 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 aPVT(CRF) 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. Animals constantly balance seeking food with avoiding predators. Here, the authors report that CRF positive neurons in the paraventricular thalamus projecting to the nucleus accumbens in rats are an indispensable component of a feedback circuit that can interrupt appetitive behaviour in favor of a defensive response in the presence of a competing threat stimulus.

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