Mood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment.

TitleMood regulation. GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment.
Publication TypeJournal Article
Year of Publication2014
AuthorsShabel, SJ, Proulx, CD, Piriz, J, Malinow, R
JournalScience
Volume345
Issue6203
Pagination1494-8
Date Published2014 Sep 19
ISSN1095-9203
KeywordsAnimals, Antidepressive Agents, Channelrhodopsins, Depression, Entopeduncular Nucleus, gamma-Aminobutyric Acid, Glutamate Decarboxylase, Glutamic Acid, Habenula, Male, Mice, Mice, Inbred C57BL, Neurons, Rats, Rats, Sprague-Dawley, Synaptic Transmission, Vesicular Glutamate Transport Protein 2
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.

DOI10.1126/science.1250469
Alternate JournalScience
PubMed ID25237099
PubMed Central IDPMC4305433
Grant ListP30 NS047101 / NS / NINDS NIH HHS / United States
R01 MH091119 / MH / NIMH NIH HHS / United States
NS047101 / NS / NINDS NIH HHS / United States