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-amino-butyric 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.

Gene Expression Changes in Glutamate and GABA-A Receptors, Neuropeptides, Ion Channels, and Cholesterol Synthesis in the Periaqueductal Gray Following Binge-Like Alcohol Drinking by Adolescent Alcohol-Preferring (P) Rats

“…Furthermore, the PAG receives a significant serotonergic innervation from the DRN involved in fight‐or‐flight behavioral responses (Johnson et al., ). Li and colleagues () reported that acute ethanol produced a robust enhancement of glutamatergic synaptic transmission in the PAG. GABA A and μ opioid receptors (Silva and Nobre, ) and glutamate receptors (Ezequiel Leite and Nobre, ; Long et al., ) within the PAG are affected in ethanol withdrawal.…”

Excitatory drive onto dopaminergic neurons in the rostral linear nucleus is enhanced by norepinephrine in an α1 adrenergic receptor-dependent manner

“…Finally, we found little to no I h current in the RLi dopamine neurons. Other groups have also found a lack of I h current in dopamine neurons with anatomical locations near the midline (Lammel et al 2011, Li et al 2013). Functionally, these properties are expected to affect differences in excitability and may influence plasticity of synaptic transmission.…”

“…Thus we analyzed the properties of these neurons in a TH-eGFP line previously utilized for analysis of dopamine neurons (Li et al 2013). In an initial characterization of the basic membrane properties of eGFP positive neurons in the RLi of these transgenic mice, we found several significant differences as compared to eGFP positive lateral VTA neurons.…”

“…Electrophysiological properties of dopamine neurons, such as action potential width and the presence of a hyperpolarization-activated current (I h ), differ based on their projection targets and anatomical location (Lammel et al 2011, Li et al 2013, Margolis et al 2008). The modulation of excitatory synapses on dopamine neurons by aversive and rewarding stimuli also depend on their projection targets (Lammel et al 2011).…”

The Bed Nucleus of the Stria Terminalis: A Critical Site of Ethanol-Induced Alterations in Neurotransmission

“…For example, the vPAG is an additional sig nificant source of dopamine input to the BNST, and therefore interactions between these regions may con tribute to outcomes following chronic ethanol exposure. Reciprocal BNSTvPAG pathways require further inves tigation as recent evidence shows that acute ethanol exposure increases the firing rate of dopamine neurons in the vPAG, perhaps by enhancing excitatory drive onto these neurons (Li, McCall, Lopez, & Kash, 2013), which could result in altered dopamine output to the BNST.…”