title: Ventral tegmental area dopamine and GABA neurons: Physiological properties and expression of mRNA for endocannabinoid biosynthetic elements.
abstract: The ventral tegmental area (VTA) is involved in adaptive reward and motivation processing and is composed of dopamine (DA) and GABA neurons. Defining the elements regulating activity and synaptic plasticity of these cells is critical to understanding mechanisms of reward and addiction. While endocannabinoids (eCBs) that potentially contribute to addiction are known to be involved in synaptic plasticity mechanisms in the VTA, where they are produced is poorly understood. In this study, DA and GABAergic cells were identified using electrophysiology, cellular markers, and a transgenic mouse model that specifically labels GABA cells. Using single-cell RT-qPCR and immunohistochemistry, we investigated mRNA and proteins involved in eCB signaling such as diacylglycerol lipase α, N-acyl-phosphatidylethanolamine-specific phospholipase D, and 12-lipoxygenase, as well as type I metabotropic glutamate receptors (mGluRs). Our results demonstrate the first molecular evidence of colocalization of eCB biosynthetic enzyme and type I mGluR mRNA in VTA neurons. Further, these data reveal higher expression of mGluR1 in DA neurons, suggesting potential differences in eCB synthesis between DA and GABA neurons. These data collectively suggest that VTA GABAergic and DAergic cells have the potential to produce various eCBs implicated in altering neuronal activity or plasticity in adaptive motivational reward or addiction.
authors.affiliation: Brigham Young University Department of Physiology and Developmental Biology Provo, UT 84602 USA.
authors.forename: Collin B
authors.initials: CB
authors.lastname: Merrill
authors.affiliation: Brigham Young University Neuroscience Center Provo, UT 84602 USA.
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Friend
authors.affiliation: Brigham Young University Neuroscience Center Provo, UT 84602 USA.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Newton
authors.affiliation: Brigham Young University Neuroscience Center Provo, UT 84602 USA.
authors.forename: Zachary H
authors.initials: ZH
authors.lastname: Hopkins
authors.affiliation: Brigham Young University Department of Physiology and Developmental Biology Provo, UT 84602 USA.|Brigham Young University Neuroscience Center Provo, UT 84602 USA.
authors.forename: Jeffrey G
authors.initials: JG
authors.lastname: Edwards
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D063388:Endocannabinoids / Q000096:biosynthesis*; D059330:GABAergic Neurons / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism; D059467:Transcriptome; D017557:Ventral Tegmental Area / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; D063388:Endocannabinoids; D009479:Neuropeptides; D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C043697:calcium-binding protein (brain); C104077:metabotropic glutamate receptor type 1; D004298:Dopamine