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Abstract:

Striatal medium spiny neurons (MSNs) form inhibitory synapses on neighboring striatal neurons through axon collaterals. The functional relevance of this lateral inhibition and its regulation by dopamine remains elusive. We show that synchronized stimulation of collateral transmission from multiple indirect-pathway MSNs (iMSNs) potently inhibits action potentials in direct-pathway MSNs (dMSNs) in the nucleus accumbens. Dopamine D2 receptors (D2Rs) suppress lateral inhibition from iMSNs to disinhibit dMSNs, which are known to facilitate locomotion. Surprisingly, D2R inhibition of synaptic transmission was larger at axon collaterals from iMSNs than their projections to the ventral pallidum. Targeted deletion of D2Rs from iMSNs impaired cocaine's ability to suppress lateral inhibition and increase locomotion. These impairments were rescued by chemogenetic activation of Gi-signaling in iMSNs. These findings shed light on the functional significance of lateral inhibition between MSNs and offer a novel synaptic mechanism by which dopamine gates locomotion and cocaine exerts its canonical stimulant response. © 2016

Registro:

Documento: Artículo
Título:Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
Autor:Dobbs, L.K.; Kaplan, A.R.; Lemos, J.C.; Matsui, A.; Rubinstein, M.; Alvarez, V.A.
Filiación:Section on Neuronal Structure, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism NIH, Bethesda, MD 20892, United States
Instituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, C1428ADN, Argentina
Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, C1428ADN, Argentina
Department of Molecular and Integrative Physiology, University of Michigan Medical School, Ann Arbor, MI 48109, United States
Palabras clave:cocaine; dopamine; dopamine 2 receptor; cocaine; dopamine; dopamine 2 receptor; adult; animal cell; animal experiment; animal tissue; Article; axon; brain nerve cell; controlled study; corpus striatum; female; gene deletion; locomotion; male; mouse; nerve potential; nerve stimulation; nerve tract; nonhuman; nucleus accumbens; priority journal; regulatory mechanism; striatal medium spiny neuron; synaptic inhibition; synaptic transmission; ventral pallidum; action potential; animal; central nervous system sensitization; corpus striatum; cytology; dose response; drug effects; knockout mouse; metabolism; nerve cell inhibition; physiology; transgenic mouse; Action Potentials; Animals; Central Nervous System Sensitization; Cocaine; Corpus Striatum; Dopamine; Dose-Response Relationship, Drug; Locomotion; Mice; Mice, Knockout; Mice, Transgenic; Neural Inhibition; Nucleus Accumbens; Receptors, Dopamine D2
Año:2016
Volumen:90
Número:5
Página de inicio:1100
Página de fin:1113
DOI: http://dx.doi.org/10.1016/j.neuron.2016.04.031
Título revista:Neuron
Título revista abreviado:Neuron
ISSN:08966273
CODEN:NERNE
CAS:cocaine, 50-36-2, 53-21-4, 5937-29-1; dopamine, 51-61-6, 62-31-7; Cocaine; Dopamine; Receptors, Dopamine D2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08966273_v90_n5_p1100_Dobbs

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Citas:

---------- APA ----------
Dobbs, L.K., Kaplan, A.R., Lemos, J.C., Matsui, A., Rubinstein, M. & Alvarez, V.A. (2016) . Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine. Neuron, 90(5), 1100-1113.
http://dx.doi.org/10.1016/j.neuron.2016.04.031
---------- CHICAGO ----------
Dobbs, L.K., Kaplan, A.R., Lemos, J.C., Matsui, A., Rubinstein, M., Alvarez, V.A. "Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine" . Neuron 90, no. 5 (2016) : 1100-1113.
http://dx.doi.org/10.1016/j.neuron.2016.04.031
---------- MLA ----------
Dobbs, L.K., Kaplan, A.R., Lemos, J.C., Matsui, A., Rubinstein, M., Alvarez, V.A. "Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine" . Neuron, vol. 90, no. 5, 2016, pp. 1100-1113.
http://dx.doi.org/10.1016/j.neuron.2016.04.031
---------- VANCOUVER ----------
Dobbs, L.K., Kaplan, A.R., Lemos, J.C., Matsui, A., Rubinstein, M., Alvarez, V.A. Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine. Neuron. 2016;90(5):1100-1113.
http://dx.doi.org/10.1016/j.neuron.2016.04.031