Cited by 390Neurotransmitter Receptor Influence on BehaviorMotor Control and AdaptationParkinson's Disease Mechanisms and Treatments

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Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey

Schultz, W.·1986·Journal of Neurophysiology

DOI 10.1152/jn.1986.56.5.1439

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Abstract

Destruction of the midbrain dopamine (DA) system in Parkinsonian man and experimental animals leads to deficits in initiation of behavior, motor performance, and cognitive mechanisms. We have investigated the extracellular impulse activity of single midbrain DA neurons in unlesioned monkeys performing in a controlled behavioral task that was designed to paradigmatically test behavioral reactivity. Animals were trained to execute natural forelimb reaching movements for food reward in response to a trigger stimulus. Presumptive DA neurons were histologically located in the pars compacta of substantia nigra and in neighboring areas A8 and A10. They spontaneously discharged polyphasic impulses of relatively long duration (1.4-3.6 ms) and at low frequencies (0.5-8.5/s). Systemic injections of low doses of the DA autoreceptor agonist apomorphine (0.05-0.2 mg/kg) depressed the activity of virtually all thus tested DA neurons. In following established criteria, these characteristics strongly suggest the DAergic nature of the recorded neurons. The majority of midbrain DA neurons (70 of 128) responded to the behavioral trigger stimulus of the task with a short burst of impulses. Latencies ranged from 39 to 105 ms (median 65 ms) for onset and from 65 to 165 ms (median 95 ms) for peak of responses. Responses occurred before arm movement and at the time of or before onset of electromyographic (EMG) activity in prime mover muscles. Responses were time-locked to the stimulus and not to the onset of movement or EMG. Responses remained present in most neurons but were reduced when vision of the behavioral trigger stimulus was prevented while maintaining the associated acoustic signals. In another variation of the task, most neurons also responded to a stimulus that was physically identical to the behavioral trigger but to which the animal made no movement. The activity of a few DA neurons (11 of 128) was reduced following presentation of the behavioral trigger stimulus, with latencies comparable to those of activations. The activity of many DA neurons was increased (40 of 128) or reduced (22 of 128) during execution of the forelimb reaching movement. These changes were of a slow and moderate nature, and were minor compared with responses to the behavioral trigger stimulus. About half of movement-related neurons also responded to the behavioral trigger. The activity of a few DA neurons was increased (11 to 128) or reduced (1 to 128) when the food reward reached the mouth. These changes did not occur with spontaneous mouth movements. About half of these neurons also responded to the behavioral trigger.(ABSTRACT TRUNCATED AT 400 WORDS)

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Subsecond dopamine fluctuations do not specify the vigor of ongoing actions
Liu, H., Melani, R., Maltese, M., Taniguchi, J., Sankaramanchi, A., Zeng, R., Martin, J. R., & Tritsch, N. X. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02102-1 · Cited by 11
“Initial investigations suggested a permissive role, since few mDANs modulate their firing during skilled movements 4,5 , and DA receptor agonists alleviate motor impairments in PD, albeit incompletely 6,7 .”
The Pathological Paradigm of Neuroeconomics
Vallois, N. (2011) · OEconomia · doi:10.4000/oeconomia.1442 · Cited by 8
Food reward and its aberrations in obesity
Hanßen, R., Schiweck, C., Aichholzer, M., Reif, A., & Thanarajah, S. E. (2022) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2022.101224 · Cited by 12
Hypocretin / Orexin Receptor 1 Knockdown in GABA or Dopamine Neurons in the Ventral Tegmental Area Differentially Impact Mesolimbic Dopamine and Motivation for Cocaine
Black, E. M., Samels, S. B., Xu, W., Barson, J. R., Bass, C. E., Kortagere, S., & España, R. A. (2023) · Addiction Neuroscience · doi:10.1016/j.addicn.2023.100104 · Cited by 8
“…the experiments presented here cannot easily reconcile these discrepant findings, it is important to note that unlike the well-described role of DA neuron firing in reward-related behaviors [104, 105–111], there is considerably less evidence for involvement of GABA neuron firing in such processes.”
Result
Calcium activity is a degraded estimate of spikes
Hart, E. E., Gardner, M., Panayi, M. C., Kahnt, T., & Schoenbaum, G. M. (2022) · Current Biology · doi:10.1016/j.cub.2022.10.037 · Cited by 12
3.4 Ion Channels and Regulation of Dopamine Neuron Activity
Liss, B., & Roeper, J. (2009) · Oxford University Press eBooks · doi:10.1093/acprof:oso/9780195373035.003.0009 · Cited by 8
Repeated phencyclidine disrupts nicotinic acetylcholine regulation of dopamine release in nucleus accumbens: Implications for models of schizophrenia
Yavas, E., & Young, A. M. J. (2020) · Neurochemistry International · doi:10.1016/j.neuint.2020.104836 · Cited by 9
Motor and cognitive functions of the neostriatum during bilateral blockade of its dopamine receptors
Shapovalova, K. B., & Kamkina, Y. V. (2007) · Neuroscience and Behavioral Physiology · doi:10.1007/s11055-008-0010-6 · Cited by 9
“In response to a new or reinforcing stimulus, these neurons generated trains of spikes with a latent period of about 100 msec [30].”
Background
Dopaminergic Involvement in Nociceptive Sensitivity/Behavioral Reactivity Regulation During Aversive States of Different Nature in the Rat
Kiyatkin, E. A. (1989) · International Journal of Neuroscience · doi:10.3109/00207458908986188 · Cited by 9
Cerebellar learning using perturbationsPreprint
Bouvier, G., Aljadeff, J., Claudia Clopath, A., Bimbard, C., Ranft, J., Blot, A., Nadal, J., Brunel, N., Hakim, V., & Barbour, B. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/053785 · Cited by 9
“It is thought that the system learns to favour the actions that maximise the (discounted) reward, which is signalled by activity bursts in dopaminergic midbrain neurones and phasic release of dopamine, notably in the striatum itself (Schultz, 1986).”
Background
Concurrent antagonism of NMDA and AMPA receptors in the ventral tegmental area reduces the expression of conditioned approach learning in rats
Hachimine, P., Seepersad, N., Babic, S., et al. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.10.054 · Cited by 8
The complex regulation of dopamine output: A review of current themes
Sulzer, D. (2005) · Clinical Neuroscience Research · doi:10.1016/j.cnr.2005.08.007 · Cited by 8
Effect of traumatic brain injury on nicotine-induced modulation of dopamine release in the striatum and nucleus accumbens shell
Chen, Y.-H., Kuo, T., Huang, E. Y., Chou, Y., Chiang, Y. H., Hoffer, B. J., & Miller, J. (2018) · Oncotarget · doi:10.18632/oncotarget.24245 · Cited by 7
“By enhancing the contrast in DA release when DA neuron activity switches from tonic to phasic firing in response to salient primary rewards or conditioned reward predictions [26], nicotine might enhance the reinforcement efficacy of any reward-related stimuli [24].”
Background
Adaptive Dopaminergic Neurons Report the Appetitive Value of Environmental Stimuli
Schultz, W. (1997) · Advances in psychology · doi:10.1016/s0166-4115(97)80103-3 · Cited by 7
Self-citation
Dopaminergic modulation of emotional memory in Parkinson’s disease
Hälbig, T. D., Kopp, U. A., Wodarz, F., Borod, J. C., Graciès, J., Ebersbach, G., & Kupsch, A. R. (2008) · Journal of Neural Transmission · doi:10.1007/s00702-008-0061-4 · Cited by 7
“Further, the observed negative effects of dopaminergic medication might at least partially depend on the type of dopaminergic medication: The physiological dopaminergic neurotransmission supporting cognitive and emotional processes is thought to be characterized by intermittent burst firing of dopaminergic neurons ( S…”
Background
Intégration de la navigation et de la sélection de l'action dans une architecture de contrôle inspirée des ganglions de la base
Girard, B. (2003) · HAL · Cited by 7
Unveiling Dopamine and Met-Enkephalin Dynamics: Simultaneous Co-Detection in Rat Striatum
Berger, J. M., Todorov, J., Turner, K. M., McCarty, G. S., Romanova, E. V., Sweedler, J. V., & Sombers, L. A. (2025) · Analytical Chemistry · doi:10.1021/acs.analchem.5c03599 · Cited by 6
Neuroprotection in late life attention-deficit/hyperactivity disorder: A review of pharmacotherapy and phenotype across the lifespan
Dutta, C. N., Christov‐Moore, L., Ombao, H., & Douglas, P. K. (2022) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2022.938501 · Cited by 8
“Interest in dopamine as a mechanism for reward-based learning and motivation gained momentum through use of electrophysiological recordings and pharmacological manipulations of DA in animals (Olds and Milner, 1954; Wise, 1982; Schultz, 1986; Schultz et al., 1993; Viggiano et al., 2003, 2004).”
Background
Involvement of cortical input to the rostromedial tegmental nucleus in aversion to foot shock
Glover, E. J., Starr, E. M., Gascon, A., Clayton-Stiglbauer, K., Amegashie, C. L., Selchick, A. H., Vaughan, D. T., Wayman, W. N., Woodward, J. J., & Chandler, L. J. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01612-5 · Cited by 8
Das menschliche Belohnungssystem
Erk, S., Walter, H., & Abler, B. (2005) · Nervenheilkunde · doi:10.1055/s-0038-1629956 · Cited by 6
“Bei Affen wurde mit Hilfe von Einzelzell-Ableitungen gezeigt, dass dopaminerge Neurone im Mittelhirn sowohl nach dem Erhalt einer Belohnung als auch nach visuellen und auditorischen Stimuli, die auf eine zukünftige Belohnung hinwiesen, verstärkt feuerten (50, 49, 34).”
Background
Fixed ratio discrimination training increases in vivo striatal dopamine in neonatal 6-OHDA-lesioned rats
Loupe, P. S., Zhou, X., Davies, M. I., Schroeder, S. R., Tessel, R. E., & Lunte, S. M. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00950-4 · Cited by 6
Alcohol Cues, Craving, and Relapse: Insights from Animal Models
Pina, M. M., & Williams, A. R. (2016) · InTech eBooks · doi:10.5772/63105 · Cited by 7
“Although VTA DA cells are initially activated by rewarding stimuli, this activation diminishes over time with repeated reward exposures and subsequent learning [112].”
Background
Evolution of in vivo dopamine monitoring techniques
Yocky, A. G., & Covey, D. P. (2020) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2020.173078 · Cited by 8
The effects of haloperidol on motor vigour and movement fusion during sequential reaching
Sporn, S., & Galea, J. M. (2025) · PLoS ONE · doi:10.1371/journal.pone.0316894 · Cited by 4
Impact of Mobile Neurofeedback on Internet Addiction and Neurocognitive Function in Neurotypical Children: Double-Blind, Sham-Controlled Randomized Clinical Trial
Choi, J.-W., Yang, S., & Kim, J. W. (2024) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s454881 · Cited by 6
“31 When unexpected rewards occur, dopamine neurons shaping the origin of the mesolimbic and mesocortical pathways are activated.”
Background
Emotional State and Feedback-Related Negativity Induced by Positive, Negative, and Combined Reinforcement
Xu, S., Sun, Y., Huang, M., Huang, Y., Han, J., Tang, X., & Ren, W. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.647263 · Cited by 6
“Previous studies showed that increased dopamine activities following unexpected presentation of food (Schultz, 1986) and successful escape from electric shock (Oleson et al., 2012; Wenzel et al., 2015) indicate, respectively, the role of dopamine in both reinforcement types.”
Background
Human substantia nigra neurons encode decision outcome and are modulated by categorization uncertainty in an auditory categorization task
McGovern, R. A., Chan, A. K.-H., Mikell, C. B., Sheehy, J. P., Ferrera, V. P., & McKhann, G. M. (2015) · Physiological Reports · doi:10.14814/phy2.12422 · Cited by 5
“When a stimulus is conditioned to predict this reward, the phasic increase in neuronal firing rate shifts to occur reliably after stimulus presentation (Schultz 1986, 1998; Schultz et al. 1997).”
BackgroundMethodResultInfluential
A role for the CD38 rs3796863 polymorphism in alcohol and monetary reward: evidence from CD38 knockout mice and alcohol self-administration, [11C]-raclopride binding, and functional MRI in humans
Lee, M. R., Shin, J. H., Deschaine, S. L., Daurio, A. M., Stangl, B. L., Yan, J., Ramchandani, V. A., Schwandt, M. L., Grodin, E. N., Momenan, R., et al. (2019) · The American Journal of Drug and Alcohol Abuse · doi:10.1080/00952990.2019.1638928 · Cited by 5
Modulatory action of dopamine on acetylcholine-responsive striatal and accumbal neurons in awake, unrestrained rats
Kiyatkin, E. A., & Rebec, G. V. (1996) · Brain Research · doi:10.1016/0006-8993(95)01487-x · Cited by 5

Authors: Schultz, W.
Corresponding author: Schultz, W.
ORCID: Schultz, W.
Venue: Journal of Neurophysiology
Publisher: American Physiological Society
Published: 1986-11-01
Volume: 56
Issue: 5
Pages: 1439-1461
ISSN: 0022-3077 (ISSN-L)
1522-1598
DOI: 10.1152/jn.1986.56.5.1439
OpenAlex: W1831076810
Cited by: 390
References: 0
Citations by year: 2026: 4 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 8 · 2020: 12 · 2019: 14 · 2018: 15 · 2017: 18 · 2016: 15 · 2015: 14 · 2014: 8 · 2013: 12 · 2012: 8
FWCI: 1.96
Type: journal article
Language: en
Open access: closed
Locations: Journal of Neurophysiology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Motor Control and Adaptation
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: midbrain dopaminergic neurons, substantia nigra pars compacta, behavioral reactivity, apomorphine, dopamine autoreceptors, food reward, single-unit activity, Parkinson's disease, monkeys
MeSH terms: Animals, Conditioning, Psychological, Dopamine, Female, Macaca fascicularis, Mesencephalon, Neurons, Reward

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Responses of midbrain dopamine neurons to behavioral trigger stimuli in the monkey

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