Chemogenetic Inhibition of Lateral Hypothalamus Inputs to the Paraventricular Thalamus Reduces Goal-Tracking in a Behaviorally Flexible Subgroup of Male Rats

The paraventricular nucleus of the thalamus has emerged as an important node in circuits regulating motivated behavior. The neuronal pathway from the lateral hypothalamus to the paraventricular thalamus has specifically been shown to regulate arousal, feeding, and reward seeking. However, the involvement of the lateral hypothalamic-paraventricular thalamic pathway in individual differences in cue-motivated behavior remains unclear. During a Pavlovian conditioned approach paradigm, when a reward is repeatedly preceded by the presentation of a cue, rats come to exhibit a conditioned response to the cue. One extreme of the population, sign-trackers, approach and interact with the cue itself; while the other extreme, goal-trackers, approach the location of reward delivery. Intermediate responders approach and interact with both the cue and reward location, without a clear preference. We utilized a Pavlovian conditioned approach paradigm to examine the effects of lateral hypothalamic-paraventricular thalamic pathway inhibition on individual differences in cue-motivated behavior. A dual-vector approach was used to selectively express inhibitory chemogenetic receptors in the lateral hypothalamic-paraventricular thalamic pathway. We found that inhibition of the pathway selectively attenuates the expression of goal-tracking behavior, without affecting sign-tracking. This effect is driven primarily by IR rats, as inhibition of lateral hypothalamic-paraventricular thalamic neurons attenuates goal-tracking behavior in intermediate responders, without impacting the response of sign-tracker or goal-trackers. We speculate that the flexibility of responding in intermediate responder rats made them especially vulnerable to this manipulation. These findings identify the lateral hypothalamic-paraventricular thalamic pathway as a selective contributor to reward-directed conditioned responding and a circuit substrate for behavioral flexibility.

Iglesias, A. G., Bhatti, J. K., Turfe, A. E., Chang, S., Liu, J., Campus, P., Flagel, S.

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