title: Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry.
abstract: Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bidirectionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia, decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers.
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Pharmacology, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Maxime
authors.initials: M
authors.lastname: Cazorla
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Pharmacology, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Fernanda Delmondes
authors.initials: FD
authors.lastname: de Carvalho
authors.affiliation: Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Muhammad O
authors.initials: MO
authors.lastname: Chohan
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Pharmacology, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Mariya
authors.initials: M
authors.lastname: Shegda
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Nao
authors.initials: N
authors.lastname: Chuhma
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Rayport
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
authors.forename: Susanne E
authors.initials: SE
authors.lastname: Ahmari
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
authors.forename: Holly
authors.initials: H
authors.lastname: Moore
authors.affiliation: Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Pharmacology, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA. Electronic address: ck491@columbia.edu.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kellendonk
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000235:genetics; D000818:Animals; D001479:Basal Ganglia / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics; D003342:Corpus Striatum / Q000166:cytology / Q000502:physiology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005917:Globus Pallidus / Q000166:cytology / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors
chemical_list: D018492:Dopamine Antagonists; C583261:Drd1 protein, mouse; C489461:Kir2.1 channel; D024661:Potassium Channels, Inwardly Rectifying; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D049452:Green Fluorescent Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D006220:Haloperidol; D004318:Doxycycline