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Roundabout receptor 2 maintains inhibitory control of the adult midbrain

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...

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Detalles Bibliográficos
Autores principales: Gore, Bryan B, Miller, Samara M, Jo, Yong Sang, Baird, Madison A, Hoon, Mrinalini, Sanford, Christina A, Hunker, Avery, Lu, Weining, Wong, Rachel O, Zweifel, Larry S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5419739/
https://www.ncbi.nlm.nih.gov/pubmed/28394253
http://dx.doi.org/10.7554/eLife.23858
Descripción
Sumario: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 of Robo2 in 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. DOI: http://dx.doi.org/10.7554/eLife.23858.001