• Leon BrownPPMaryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Ave., Catonsville, MD 21228, USA. Electronic address: plbrown@som.umaryland.edu., Heather Palacorolla, Dana E Cobb-Lewis, Thomas C Jhou, Pat McMahon, Dana Bell, Greg I Elmer, and Paul D Shepard.
• Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, 55 Wade Ave., Catonsville, MD 21228, USA. Electronic address: plbrown@som.umaryland.edu.
• Neuroscience. 2024 Apr 16.

AbstractDopamine (DA) neurons of the substantia nigra (SN) and ventral tegmental area generally respond to aversive stimuli or the absence of expected rewards with transient inhibition of firing rates, which can be recapitulated with activation of the lateral habenula (LHb) and eliminated by lesioning the intermediating rostromedial tegmental nucleus (RMTg). However, a minority of DA neurons respond to aversive stimuli, such as foot shock, with a transient increase in firing rate, an outcome that rarely occurs with LHb stimulation. The degree to which individual neurons respond to these two stimulation modalities with the same response phenotype and the role of the RMTg is not known. Here, we record responses from single SN DA neurons to alternating activation of the LHb and foot shock in male rats. Lesions of the RMTg resulted in a shift away from inhibition to no response during both foot shock and LHb stimulation. Furthermore, lesions unmasked an excitatory response during LHb stimulation. The response correspondence within the same neuron between the two activation sources was no different from chance in sham controls, suggesting that external inputs rather than intrinsic DA neuronal properties are more important to response outcome. These findings contribute to a literature that shows a complex neurocircuitry underlies the regulation of DA activity and, by extension, behaviors related to learning, anhedonia, and cognition.Copyright © 2024 IBRO. Published by Elsevier Inc. All rights reserved.

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