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Activity-dependent somatodendritic dopamine release in the substantia nigra autoinhibits the releasing neuron.
- Source :
-
Cell reports [Cell Rep] 2021 Apr 06; Vol. 35 (1), pp. 108951. - Publication Year :
- 2021
-
Abstract
- Somatodendritic dopamine (DA) release from midbrain DA neurons activates D2 autoreceptors on these cells to regulate their activity. However, the source of autoregulatory DA remains controversial. Here, we test the hypothesis that D2 autoreceptors on a given DA neuron in the substantia nigra pars compacta (SNc) are activated primarily by DA released from that same cell, rather than from its neighbors. Voltage-clamp recording allows monitoring of evoked D2-receptor-mediated inhibitory currents (D2ICs) in SNc DA neurons as an index of DA release. Single-cell application of antibodies to Na <superscript>+</superscript> channels via the recording pipette decreases spontaneous activity of recorded neurons and attenuates evoked D2ICs; antibodies to SNAP-25, a soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) protein, also decrease D2IC amplitude. Evoked D2ICs are nearly abolished by the light chain of botulinum neurotoxin A, which cleaves SNAP-25, whereas synaptically activated GABA <subscript>B</subscript> -receptor-mediated currents are unaffected. Thus, somatodendritic DA release in the SNc autoinhibits the neuron that releases it.<br />Competing Interests: Declaration of interests K.I. is the founder of and has financial interests in CytoDel, Inc., a biopharmaceutical company with license to NYU patents that protect the work related to BoNT/A constructs used in this report.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antibodies metabolism
Electric Stimulation
Inhibitory Postsynaptic Potentials
Kinetics
Male
Mice, Inbred C57BL
Receptors, Dopamine D2 metabolism
Single-Cell Analysis
Synaptosomal-Associated Protein 25 metabolism
Voltage-Gated Sodium Channels metabolism
gamma-Aminobutyric Acid metabolism
Mice
Dendrites metabolism
Dopamine metabolism
Substantia Nigra metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2211-1247
- Volume :
- 35
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Cell reports
- Publication Type :
- Academic Journal
- Accession number :
- 33826884
- Full Text :
- https://doi.org/10.1016/j.celrep.2021.108951