title: Mood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment.
abstract: The lateral habenula (LHb), a key regulator of monoaminergic brain regions, is activated by negatively valenced events. Its hyperactivity is associated with depression. Although enhanced excitatory input to the LHb has been linked to depression, little is known about inhibitory transmission. We discovered that γ-aminobutyric acid (GABA) is co-released with its functional opponent, glutamate, from long-range basal ganglia inputs (which signal negative events) to limit LHb activity in rodents. At this synapse, the balance of GABA/glutamate signaling is shifted toward reduced GABA in a model of depression and increased GABA by antidepressant treatment. GABA and glutamate co-release therefore controls LHb activity, and regulation of this form of transmission may be important for determining the effect of negative life events on mood and behavior.
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA. sshabel@gmail.com.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Shabel
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA.
authors.forename: Christophe D
authors.initials: CD
authors.lastname: Proulx
authors.affiliation: Grupo de Neurociencia de Sistemas, Instituto de Fisiología y Biofísica Houssay (CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Joaquin
authors.initials: J
authors.lastname: Piriz
authors.affiliation: Center for Neural Circuits and Behavior, Department of Neuroscience and Section of Neurobiology, Division of Biology, University of California at San Diego, San Diego, CA, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Malinow
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D000075402:Channelrhodopsins; D003863:Depression / Q000378:metabolism*; D020392:Entopeduncular Nucleus / Q000187:drug effects / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D019262:Habenula / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D050599:Vesicular Glutamate Transport Protein 2 / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D000075402:Channelrhodopsins; C493477:Slc17a6 protein, mouse; D050599:Vesicular Glutamate Transport Protein 2; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1