The lateral hypothalamus and orexinergic transmission in the paraventricular thalamus promote the attribution of incenti
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ORIGINAL INVESTIGATION
The lateral hypothalamus and orexinergic transmission in the paraventricular thalamus promote the attribution of incentive salience to reward-associated cues Joshua L. Haight 1,2 & Paolo Campus 3 & Cristina E Maria-Rios 1 & Allison M. Johnson 4 & Marin S. Klumpner 5 & Brittany N. Kuhn 1,6 & Ignacio R. Covelo 5,7 & Jonathan D. Morrow 1,5 & Shelly B. Flagel 1,3,4,5 Received: 8 April 2020 / Accepted: 20 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Rationale Prior research suggests that the neural pathway from the lateral hypothalamic area (LHA) to the paraventricular nucleus of the thalamus (PVT) mediates the attribution of incentive salience to Pavlovian reward cues. However, a causal role for the LHA and the neurotransmitters involved have not been demonstrated in this regard. Objectives To examine (1) the role of LHA in the acquisition of Pavlovian conditioned approach (PavCA) behaviors, and (2) the role of PVT orexin 1 receptors (OX1r) and orexin 2 receptors (OX2r) in the expression of PavCA behaviors and conditioned reinforcement. Methods Rats received excitotoxic lesions of the LHA prior to Pavlovian training. A separate cohort of rats characterized as signtrackers (STs) or goal-trackers (GTs) received the OX1r antagonist SB-334867, or the OX2r antagonist TCS-OX2-29, into the PVT, to assess their effects on the expression of PavCA behavior and on the conditioned reinforcing properties of a Pavlovian reward cue. Results LHA lesions attenuated the development of sign-tracking behavior. Administration of either the OX1r or OX2r antagonist into the PVT reduced sign-tracking behavior in STs. Further, OX2r antagonism reduced the conditioned reinforcing properties of a Pavlovian reward cue in STs. Conclusions The LHA is necessary for the development of sign-tracking behavior; and blockade of orexin signaling in the PVT attenuates the expression of sign-tracking behavior and the conditioned reinforcing properties of a Pavlovian reward cue. Together, these data suggest that LHA orexin inputs to the PVT are a key component of the circuitry that encodes the incentive motivational value of reward cues. Keywords Incentive salience . Paraventricular nucleus of the thalamus . Lateral hypothalamus . Sign-tracking . Orexin/hypocretin
Joshua L Haight and Paolo Campus are co-first authors. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00213-020-05651-4) contains supplementary material, which is available to authorized users. * Shelly B. Flagel [email protected]
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Undergraduate Program in Neuroscience, University of Michigan, 1140 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI 48109, USA
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Neuroscience Graduate Program, University of Michigan, 4137 Undergraduate Science Building, 204 Washtenaw Avenue, Ann Arbor, MI 48109, USA
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Department of Psychiatry, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48105, USA
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Department of Psychology, Quinnipiac University, 275 Mt Carmel Avenu
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