title: Alcohol effects on synaptic transmission in periaqueductal gray dopamine neurons.
abstract: The role of dopamine (DA) signaling in regulating the rewarding properties of drugs, including alcohol, has been widely studied. The majority of these studies, however, have focused on the DA neurons located in the ventral tegmental area (VTA), and their projections to the nucleus accumbens. DA neurons within the ventral periaqueductal gray (vPAG) have been shown to regulate reward but little is known about the functional properties of these neurons, or how they are modified by drugs of abuse. This lack of knowledge is likely due to the highly heterogeneous cell composition of the vPAG, with both γ-aminobutyric acid (GABA) and glutamate neurons present in addition to DA neurons. In this study, we performed whole-cell recordings in a TH-eGFP transgenic mouse line to evaluate the properties of vPAG-DA neurons. Following this initial characterization, we examined how both acute and chronic alcohol exposure modify synaptic transmission onto vPAG-DA neurons. We found minimal effects of acute alcohol exposure on GABA transmission, but a robust enhancement of glutamatergic synaptic transmission in vPAG-DA. Consistent with this effect on excitatory transmission, we also found that alcohol caused an increase in firing rate. These data were in contrast to the effects of chronic intermittent alcohol exposure, which had no significant impact on either inhibitory or excitatory synaptic transmission on the vPAG-DA neurons. These data add to a growing body of literature that points to alcohol having both region-dependent and cell-type dependent effects on function.
authors.affiliation: Curriculum in Neurobiology, University of North Carolina-Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Chia
authors.initials: C
authors.lastname: Li
authors.forename: Nora M
authors.initials: NM
authors.lastname: McCall
authors.forename: Alberto J
authors.initials: AJ
authors.lastname: Lopez
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
mesh_terms: D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000378:metabolism; D000431:Ethanol / Q000737:chemistry / Q000633:toxicity*; D019706:Excitatory Postsynaptic Potentials; D018698:Glutamic Acid / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D019570:Inhalation Exposure; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials; D018408:Patch-Clamp Techniques; D010487:Periaqueductal Gray / Q000187:drug effects* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism; D014835:Volatilization; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011993:Recombinant Fusion Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000431:Ethanol; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D014446:Tyrosine 3-Monooxygenase