title: Roundabout receptor 2 maintains inhibitory control of the adult midbrain.
abstract: The maintenance of excitatory and inhibitory balance in the brain is essential for its function. Here we find that the developmental axon guidance receptor Roundabout 2 (Robo2) is critical for the maintenance of inhibitory synapses in the adult ventral tegmental area (VTA), a brain region important for the production of the neurotransmitter dopamine. Following selective genetic inactivation ofRobo2in the adult VTA of mice, reduced inhibitory control results in altered neural activity patterns, enhanced phasic dopamine release, behavioral hyperactivity, associative learning deficits, and a paradoxical inversion of psychostimulant responses. These behavioral phenotypes could be phenocopied by selective inactivation of synaptic transmission from local GABAergic neurons of the VTA, demonstrating an important function for Robo2 in regulating the excitatory and inhibitory balance of the adult brain.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, United States.|Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Bryan B
authors.initials: BB
authors.lastname: Gore
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Samara M
authors.initials: SM
authors.lastname: Miller
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, United States.|Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Yong Sang
authors.initials: YS
authors.lastname: Jo
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Madison A
authors.initials: MA
authors.lastname: Baird
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, United States.
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Hoon
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Christina A
authors.initials: CA
authors.lastname: Sanford
authors.affiliation: Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Avery
authors.initials: A
authors.lastname: Hunker
authors.affiliation: Department of Medicine, Renal Section, Boston University Medical Center, Boston, United States.
authors.forename: Weining
authors.initials: W
authors.lastname: Lu
authors.affiliation: Department of Biological Structure, University of Washington, Seattle, United States.
authors.forename: Rachel O
authors.initials: RO
authors.lastname: Wong
authors.affiliation: Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, United States.|Department of Pharmacology, University of Washington, Seattle, United States.
authors.forename: Larry S
authors.identifier: 0000-0003-3465-5331
authors.initials: LS
authors.lastname: Zweifel
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D055786:Gene Knockout Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D011971:Receptors, Immunologic / Q000378:metabolism*; D009435:Synaptic Transmission; D017557:Ventral Tegmental Area / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D004298:Dopamine; D011971:Receptors, Immunologic; D005680:gamma-Aminobutyric Acid; C498888:Robo2 protein, mouse; D000097905:Roundabout Proteins
keywords: GABA; Robo2; dopamine; electrophysiology; genetics; mouse; neuroscience