@article {11153,
	title = {Ethanol experience enhances glutamatergic ventral hippocampal inputs to D1 receptor-expressing medium spiny neurons in the nucleus accumbens shell.},
	journal = {Journal of Neuroscience},
	volume = {39},
	year = {2019},
	pages = {2459-2469},
	abstract = {
	A growing number of studies implicate alterations in\&nbsp;glutamatergic\&nbsp;signaling within the reward circuitry of the brain during alcohol abuse and dependence. A key integrator of\&nbsp;glutamatergic\&nbsp;signaling in the reward circuit is the\&nbsp;nucleus\&nbsp;accumbens, more specifically, the dopamine\&nbsp;D1\&nbsp;receptor-expressing\&nbsp;medium\&nbsp;spiny\&nbsp;neurons\&nbsp;(D1-MSNs) within this region, which have been implicated in the formation of dependence to many drugs of abuse including alcohol.\&nbsp;D1-MSNs receive\&nbsp;glutamatergicinput from several brain regions; however, it is not currently known how individual\&nbsp;inputs\&nbsp;onto\&nbsp;D1-MSNs are altered by alcohol\&nbsp;experience. Here, we investigate input-specific adaptations in\&nbsp;glutamatergic\&nbsp;transmission in response to varying levels of alcohol\&nbsp;experience. Virally mediated expression of Channelrhodopsin in\&nbsp;ventral\&nbsp;hippocampal\&nbsp;(vHipp) glutamate\&nbsp;neurons\&nbsp;of male mice allowed for selective activation of vHipp to\&nbsp;D1-MSN synapses. Therefore, we were able to compare synaptic adaptations in response to low and high alcohol\&nbsp;experience\&nbsp;in vitro\&nbsp;and\&nbsp;in vivo\&nbsp;Alcohol\&nbsp;experience\&nbsp;enhanced\&nbsp;glutamatergic\&nbsp;activity and abolished LTD at vHipp to\&nbsp;D1-MSN synapses. Following chronic alcohol\&nbsp;experience, GluA2-lacking AMPARs, which are Ca permeable, were inserted into vHipp to\&nbsp;D1-MSN synapses. These findings support the reversal of alcohol-induced insertion of Ca-permeable AMPARs and the enhancement of\&nbsp;glutamatergic\&nbsp;activity at vHipp to\&nbsp;D1-MSNs as potential targets for intervention during early exposure to alcohol.\&nbsp;SIGNIFICANCE STATEMENT\&nbsp;Given the roles of the\&nbsp;nucleus\&nbsp;accumbens\&nbsp;(NAc) in integrating cortical and allocortical information and in reward learning, it is vital to understand how\&nbsp;inputs\&nbsp;to this region are altered by drugs of abuse such as alcohol. The strength of excitatory\&nbsp;inputs\&nbsp;from the\&nbsp;ventral\&nbsp;hippocampus (vHipp) to the NAc has been positively associated with reward-related behaviors, but it is unclear whether or how\&nbsp;ethanol\&nbsp;affects these\&nbsp;inputs. Here we show that vHipp-NAc synapses indeed are altered by\&nbsp;ethanolexposure, with vHipp\&nbsp;glutamatergic\&nbsp;input to the NAc being enhanced following chronic\&nbsp;ethanol\&nbsp;experience. This work provides insight into\&nbsp;ethanol-induced alterations of vHipp-NAc synapses and suggests that, similarly to drugs such as cocaine, the strengthening of these synapses promotes reward behavior.

},
	url = {http://www.jneurosci.org/content/39/13/2459.long},
	author = {Kircher, DM and Aziz, HC and Mangieri, RA and Morrisett, RA}
}
