Segregated cholinergic transmission modulates dopamine neurons integrated in distinct functional circuits

被引:125
作者
Dautan, Daniel [1 ,2 ,3 ]
Souza, Albert S. [1 ,8 ]
Huerta-Ocampo, Icnelia [1 ,3 ]
Valencia, Miguel [3 ,4 ,5 ]
Assous, Maxime [3 ]
Witten, Ilana B. [6 ]
Deisseroth, Karl [7 ]
Tepper, James M. [3 ]
Bolam, J. Paul [1 ]
Gerdjikov, Todor V. [2 ]
Mena-Segovia, Juan [1 ,3 ]
机构
[1] Univ Oxford, Dept Pharmacol, MRC Anat Neuropharmacol Unit, Oxford, England
[2] Univ Leicester, Sch Psychol, Leicester, Leics, England
[3] Rutgers State Univ, Ctr Mol & Behav Neurosci, Newark, NJ 07102 USA
[4] Univ Navarra, CIMA, Pamplona, Spain
[5] Navarra Inst Hlth Res, diSNA, Pamplona, Spain
[6] Princeton Neurosci Inst, Princeton, NJ USA
[7] Stanford Univ, Dept Psychiat, Stanford, CA 94305 USA
[8] Univ Fed Mato Grosso do Sul, Campo Grande, MS, Brazil
基金
英国医学研究理事会;
关键词
VENTRAL TEGMENTAL AREA; NIGRA PARS COMPACTA; PEDUNCULOPONTINE NUCLEUS; MUSCARINIC RECEPTORS; PONTOMESENCEPHALIC TEGMENTUM; BASAL GANGLIA; BRAIN-STEM; IN-VITRO; RAT; MIDBRAIN;
D O I
10.1038/nn.4335
中图分类号
Q189 [神经科学];
学科分类号
071006 [神经生物学];
摘要
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.
引用
收藏
页码:1025 / +
页数:14
相关论文
共 66 条
[1]
Expression of neuronal nicotinic acetylcholine receptor subunit mRNAs within midbrain dopamine neurons [J].
Azam, L ;
Winzer-Serhan, UH ;
Chen, YL ;
Leslie, FM .
JOURNAL OF COMPARATIVE NEUROLOGY, 2002, 444 (03) :260-274
[2]
BEVAN MD, 1995, J NEUROSCI, V15, P7105
[3]
Statistical method for detection of firing rate changes in spontaneously active neurons [J].
Blejec, A .
NEUROCOMPUTING, 2005, 65 :557-563
[4]
COLLATERAL AXONS OF CHOLINERGIC PONTINE NEURONS PROJECTING TO MIDLINE, MEDIODORSAL AND PARAFASCICULAR THALAMIC NUCLEI IN THE RAT [J].
BOLTON, RF ;
CORNWALL, J ;
PHILLIPSON, OT .
JOURNAL OF CHEMICAL NEUROANATOMY, 1993, 6 (02) :101-114
[5]
Discharge Profiles across the Sleep-Waking Cycle of Identified Cholinergic, GABAergic, and Glutamatergic Neurons in the Pontomesencephalic Tegmentum of the Rat [J].
Boucetta, Soufiane ;
Cisse, Youssouf ;
Mainville, Lynda ;
Morales, Marisela ;
Jones, Barbara E. .
JOURNAL OF NEUROSCIENCE, 2014, 34 (13) :4708-4727
[6]
Phasic excitation of dopamine neurons in ventral VTA by noxious stimuli [J].
Brischoux, Frederic ;
Chakraborty, Subhojit ;
Brierley, Daniel I. ;
Ungless, Mark A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (12) :4894-4899
[7]
Dopamine in Motivational Control: Rewarding, Aversive, and Alerting [J].
Bromberg-Martin, Ethan S. ;
Matsumoto, Masayuki ;
Hikosaka, Okihide .
NEURON, 2010, 68 (05) :815-834
[8]
Ventral tegmental area GABA projections pause accumbal cholinergic interneurons to enhance associative learning [J].
Brown, Matthew T. C. ;
Tan, Kelly R. ;
O'Connor, Eoin C. ;
Nikonenko, Irina ;
Muller, Dominique ;
Luescher, Christian .
NATURE, 2012, 492 (7429) :452-456
[9]
NICOTINIC EXCITATION OF RAT VENTRAL TEGMENTAL NEURONS INVITRO STUDIED BY INTRACELLULAR-RECORDING [J].
CALABRESI, P ;
LACEY, MG ;
NORTH, RA .
BRITISH JOURNAL OF PHARMACOLOGY, 1989, 98 (01) :135-140
[10]
Charara A, 1996, J COMP NEUROL, V364, P254