University of Leicester
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Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits.

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journal contribution
posted on 2016-11-29, 10:14 authored by Daniel Dautan, A. S. Souza, I. Huerta-Ocampo, M. Valencia, M. Assous, I. B. Witten, K. Deisseroth, J. M. Tepper, J. P. Bolam, Todor V. Gerdjikov, J. Mena-Segovia
Dopamine neurons in the ventral tegmental area (VTA) receive cholinergic innervation from brainstem structures that are associated with either movement or reward. Whereas cholinergic neurons of the pedunculopontine nucleus (PPN) carry an associative/motor signal, those of the laterodorsal tegmental nucleus (LDT) convey limbic information. We used optogenetics and in vivo juxtacellular recording and labeling to examine the influence of brainstem cholinergic innervation of distinct neuronal subpopulations in the VTA. We found that LDT cholinergic axons selectively enhanced the bursting activity of mesolimbic dopamine neurons that were excited by aversive stimulation. In contrast, PPN cholinergic axons activated and changed the discharge properties of VTA neurons that were integrated in distinct functional circuits and were inhibited by aversive stimulation. Although both structures conveyed a reinforcing signal, they had opposite roles in locomotion. Our results demonstrate that two modes of cholinergic transmission operate in the VTA and segregate the neurons involved in different reward circuits.


This work was supported by the Medical Research Council UK and by a Leverhulme Trust grant to J.M.-S. and T.V.G. (RPG-2012-690). D.D. was funded by a University of Leicester PhD studentship. A.S.S. was supported by People Marie Curie Actions: Latin America and Europe Liaison and Universidade Federal de Mato Grosso do Sul.



Nature Neuroscience, 2016, 19 (8), pp. 1025-1033

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/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/MBSP Non-Medical Departments/Neuroscience, Psychology and Behaviour


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The data that support the findings of this study and the custom Matlab code are available from corresponding author on request. 6 Month embargo for full text.



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