Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine
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 i...
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paper:paper_08966273_v90_n5_p1100_Dobbs2023-06-08T15:49:13Z Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine Rubinstein, Marcelo 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 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 Fil:Rubinstein, M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2016 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08966273_v90_n5_p1100_Dobbs http://hdl.handle.net/20.500.12110/paper_08966273_v90_n5_p1100_Dobbs |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Rubinstein, Marcelo Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| topic_facet |
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 |
| description |
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 |
| author |
Rubinstein, Marcelo |
| author_facet |
Rubinstein, Marcelo |
| author_sort |
Rubinstein, Marcelo |
| title |
Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| title_short |
Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| title_full |
Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| title_fullStr |
Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| title_full_unstemmed |
Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine |
| title_sort |
dopamine regulation of lateral inhibition between striatal neurons gates the stimulant actions of cocaine |
| publishDate |
2016 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_08966273_v90_n5_p1100_Dobbs http://hdl.handle.net/20.500.12110/paper_08966273_v90_n5_p1100_Dobbs |
| work_keys_str_mv |
AT rubinsteinmarcelo dopamineregulationoflateralinhibitionbetweenstriatalneuronsgatesthestimulantactionsofcocaine |
| _version_ |
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