title: Basal Ganglia Output Controls Active Avoidance Behavior.
abstract: Engrained avoidance behavior is highly adaptive when it keeps away harmful events and can be highly maladaptive when individuals elude harmless situations in anxiety disorders, but the neural circuits that mediate avoidance are poorly understood. Using DREADDs and optogenetics in mice, we show that the output of the basal ganglia through the substantia nigra pars reticulata (SNr) controls active avoidance. SNr excitation blocks avoidance to a conditioned sensory stimulus while preserving the ability to escape the harmful event. Conversely, SNr inhibition facilitates avoidance to the conditioned stimulus and suffices to drive avoidance without any conditioned sensory stimulus. The results highlight a midbrain circuit that gates avoidance responses, which can be targeted to ameliorate maladaptive avoidance in psychiatric disorders.
  
  
  
  In many circumstances, subjects respond to fearful situations with avoidance. This is a useful coping strategy in situations in which there is impending danger. However, avoidance responses can also be maladaptive, as in anxiety disorders such as phobias (e.g., avoiding air transportation) and social anxiety (e.g., avoiding social situations). Despite the obvious clinical relevance, little is known about the neural circuits that mediate active avoidance. Using chemogenetics and optogenetics, we show that the output of the basal ganglia fully controls active avoidance behavior.
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hormigo
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
authors.forename: German
authors.initials: G
authors.lastname: Vega-Flores
authors.affiliation: Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, Pennsylvania 19129.
authors.forename: Manuel A
authors.identifier: 0000-0002-2916-9585
authors.initials: MA
authors.lastname: Castro-Alamancos
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001479:Basal Ganglia / Q000502:physiology*; D055724:Electrophysiological Phenomena / Q000502:physiology; D005239:Fear / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000502:physiology; D062308:Optogenetics; D065841:Pars Reticulata / Q000502:physiology; D040901:Proteomics
keywords: approach; avoidance; escape; midbrain; substantia nigra; superior colliculus