Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry

Maxime Cazorla; Fernanda Delmondes de Carvalho; Muhammad O Chohan; Mariya Shegda; Nao Chuhma; Stephen Rayport; Susanne E Ahmari; Holly Moore; Christoph Kellendonk

doi:10.1016/j.neuron.2013.10.041

Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry

Neuron. 2014 Jan 8;81(1):153-64. doi: 10.1016/j.neuron.2013.10.041.

Authors

Maxime Cazorla¹, Fernanda Delmondes de Carvalho¹, Muhammad O Chohan², Mariya Shegda¹, Nao Chuhma³, Stephen Rayport³, Susanne E Ahmari⁴, Holly Moore⁵, Christoph Kellendonk⁶

Affiliations

¹ 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.
² Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
³ Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Molecular Therapeutics, New York State Psychiatric Institute, New York, NY 10032, USA.
⁴ Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15213, USA.
⁵ Department of Psychiatry, Columbia University, New York, NY 10032, USA; Department of Integrative Neuroscience, New York State Psychiatric Institute, New York, NY 10032, USA.
⁶ 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.

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.

MeSH terms

Action Potentials / drug effects
Action Potentials / genetics
Animals
Basal Ganglia / cytology*
Basal Ganglia / drug effects
Basal Ganglia / physiology
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics
Corpus Striatum / cytology
Corpus Striatum / physiology
Dopamine Antagonists / pharmacology
Doxycycline / pharmacology
Gene Expression Regulation / drug effects
Gene Expression Regulation / genetics
Globus Pallidus / cytology
Globus Pallidus / physiology
Green Fluorescent Proteins / genetics
Green Fluorescent Proteins / metabolism
Haloperidol / pharmacology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Mutation / genetics
Nerve Net / drug effects
Nerve Net / physiology*
Neural Pathways / drug effects
Neural Pathways / physiology*
Neurons / drug effects
Neurons / physiology*
Potassium Channels, Inwardly Rectifying / genetics
Potassium Channels, Inwardly Rectifying / metabolism
Receptors, Dopamine D1 / genetics
Receptors, Dopamine D2 / deficiency
Receptors, Dopamine D2 / physiology*
Time Factors

Substances

Dopamine Antagonists
Drd1 protein, mouse
Kir2.1 channel
Potassium Channels, Inwardly Rectifying
Receptors, Dopamine D1
Receptors, Dopamine D2
Green Fluorescent Proteins
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Haloperidol
Doxycycline

Abstract

MeSH terms

Substances

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