RT Journal Article
SR Electronic
T1 Dopamine receptors differentially control binge alcohol drinking-mediated synaptic plasticity of the core nucleus accumbens direct and indirect pathways
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3845-16
DO 10.1523/JNEUROSCI.3845-16.2017
A1 Xincai Ji
A1 Sucharita Saha
A1 Jenya Kolpakova
A1 Melissa Guildford
A1 Andrew R Tapper
A1 Gilles E. Martin
YR 2017
UL http://www.jneurosci.org/content/early/2017/05/03/JNEUROSCI.3845-16.2017.abstract
AB Binge alcohol drinking, a behavior characterized by rapid repeated alcohol intakes, is most prevalent in young adults and a risk factor for excessive alcohol consumption and alcohol dependence. Although alteration of synaptic plasticity is thought to contribute to this behavior, there is currently little evidence that this is the case. We used drinking-in-the-dark (DID) as a model of binge alcohol drinking to assess its effects on spike-timing-dependent plasticity (STDP) in medium spiny neurons (MSNs) of the core nucleus accumbens (NAc) by combining patch clamp recordings with calcium imaging and optogenetics. After 2 weeks of daily alcohol binges, synaptic plasticity was profoundly altered. STDP in MSNs expressing dopamine D1 receptors (D1R(+)) shifted from tLTD, the predominant form of plasticity in naïve male mice, to tLTP in DID mice, an effect that was totally reversed in the presence of 4 μM SCH23390, a dopamine D1 receptor antagonist. In MSNs presumably expressing dopamine D2 receptors (D1R(-)), tLTP, the main form of plasticity in naïve mice, was inhibited in DID mice. Interestingly, 1 μM Sulpiride, a D2 receptor antagonist restored tLTP. Although we observed no alterations of AMPA and NMDA receptor properties, we found that the AMPA/NMDA ratio increased at cortical and amygdala, but not at hippocampal inputs. Also, DID effects on STDP were accompanied by lower dendritic calcium transients. These data suggest that the role of dopamine in mediating the effects of binge alcohol drinking on synaptic plasticity of NAc MSNs differs markedly whether these neurons belong to the direct or indirect pathways.Significant statementWe examined the relationship between binge alcohol drinking and spike-timing-dependent plasticity in nucleus accumbens neurons. We found that repeated drinking bouts modulate differently synaptic plasticity in medium spiny neurons of the accumbens direct and indirect pathways. While tLTD switches to LTP in the former, tLTP is inhibited in the latter. These effects are not accompanied by changes of AMPA and NMDA receptor properties at cortical, amygdala and hippocampal synapses. Interestingly, dopamine D1 and D2 receptor antagonists have opposite effects on plasticity. Our data show that whether core NAc MSNs belong to the direct or indirect pathways determines the form of STDP, the manner by which STDP responds to binge alcohol drinking, and its sensitivity to dopamine receptor antagonists.