Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons

Henny, Pablo; Brown, Matthew T C; Northrop, Augustus; Faunes, Macarena; Ungless, Mark A; Magill, Peter J; Bolam, J Paul

doi:10.1038/nn.3048

Cited by 139Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeurological disorders and treatments

Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons

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Henny, Pablo, Brown, Matthew T C, Northrop, Augustus, Faunes, Macarena, Ungless, Mark A, Magill, Peter J, Bolam, J Paul·2012·Nature Neuroscience

DOI 10.1038/nn.3048PMC PMC4242968

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Abstract

Dopaminergic neurons of the substantia nigra pars compacta (SNc) exhibit functional heterogeneity that likely underpins their diverse roles in behavior. We examined how the functional diversity of identified dopaminergic neurons in vivo correlates with differences in somato-dendritic architecture and afferent synaptic organization. Stereological analysis of individually recorded and labeled dopaminergic neurons of rat SNc revealed that they received approximately 8,000 synaptic inputs, at least 30% of which were glutamatergic and 40-70% were GABAergic. The latter synapses were proportionally greater in number and denser on dendrites located in the substantia nigra pars reticulata (SNr) than on those located in SNc, revealing the existence of two synaptically distinct and region-specific subcellular domains. We also found that the relative extension of SNc neuron dendrites into the SNr dictated overall GABAergic innervation and predicted inhibition responses to aversive stimuli. We conclude that diverse wiring patterns determine the heterogeneous activities of midbrain dopaminergic neurons in vivo.

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The majority of afferents onto DA neurons of the VTA-as much as 70% of synaptic inputs-are GABAergic and have a major impact on the activity of DA cells.
“Given that the majority of afferents onto DA neurons of the VTA -as much as 70 % of synaptic inputs -are GABAergic and have a major impact on the activity of DA cells (Henny et al., 2012; Mathon et al., 2003; White, 1996; Yang et al., 2018)”
From Nilotinib restores memory function by preventing dopaminergic neuron degeneration in a mouse model of Alzheimer’s Disease (2021) · cites this paper as Henny et al., 2012
Aversive events recruit subpopulations of DA neurons to contribute to learning and memory.
“These results support the hypothesis that aversive events recruit subpopulations of DA neurons (Brischoux et al., 2009; Henny et al., 2012; Lammel et al., 2011; Lammel et al., 2014; Lammel et al., 2012) to contribute to learning and memory.”
From Dopamine regulates aversive contextual learning and associated in vivo synaptic plasticity in the Hippocampus (2016) · cites this paper as Henny et al., 2012

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Zahm (1996) · doi:10.1002/(sici)1096-9861(19960108)364:2

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[20]Fallon JH Loughlin SE Paxinos G Substantia nigra The Rat Nervous System 1995 215 238 Academic Press London

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Authors: Henny, P., Brown, M. T. C., Northrop, A., Faunes, M., Ungless, M. A., Magill, P. J., & Bolam, J. P.
Affiliations: Pontificia Universidad Católica de Chile (CL)
Hammersmith Hospital (GB)
University of Oxford (GB)
Corresponding author: Henny, Pablo
ORCID: Henny, Pablo
Brown, Matthew T C
Faunes, Macarena
Ungless, Mark A
Magill, Peter J
Bolam, J Paul
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2012-02-12
Volume: 15
Issue: 4
Pages: 613-619
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/nn.3048
PMC: PMC4242968
OpenAlex: W2075511856
Cited by: 139
References: 49
Citations by year: 2026: 5 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 6 · 2021: 11 · 2020: 4 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 17 · 2015: 14 · 2014: 16 · 2013: 10 · 2012: 7
FWCI: 6.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Americanae (AECID Library) (submittedVersion, other-oa)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
Funders: Parkinson's UK (G-0601)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Neurology › Neurological disorders and treatments
Keywords: midbrain dopaminergic neurons, substantia nigra pars compacta, substantia nigra pars reticulata, neuronal heterogeneity, dendritic ultrastructure, glutamatergic synaptic input, aversive stimuli, neuronal inhibition, juxtacellular labeling, stereology
MeSH terms: Action Potentials, Animals, Mesencephalon, Physical Stimulation, Synapses, Rats, Dopaminergic Neurons

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Structural correlates of heterogeneous in vivo activity of midbrain dopaminergic neurons

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