Abstract
The dorsal striatum is a brain region involved in action control, with dorsomedial striatum (DMS) mediating goal-directed actions and dorsolateral striatum (DLS) mediating habitual actions. Presynaptic long-term synaptic depression (LTD) plasticity at glutamatergic inputs to dorsal striatum mediates many dorsal striatum-dependent behaviors and disruption of LTD influences action control. Our previous work identified mu opioid receptors (MORs) as mediators of synapse-specific forms of synaptic depression at a number of different DLS synapses. We demonstrated that anterior insular cortex inputs are the sole inputs that express alcohol-sensitive MOR-mediated LTD (mOP-LTD) in DLS. Here, we explore mOP-LTD in DMS using mouse brain slice electrophysiology. We found that contrary to DLS, DMS mOP-LTD is induced by activation of MORs at inputs from both anterior cingulate and medial prefrontal cortices as well as at basolateral amygdala inputs and striatal cholinergic interneuron synapses on to DMS medium spiny neurons, suggesting that MOR synaptic plasticity in DMS is less synapse-specific than in DLS. Furthermore, only mOP-LTD at cortical inputs was sensitive to alcohol’s deleterious effects. These results suggest that alcohol-induced neuroadaptations are differentially expressed in a synapse-specific manner and could be playing a role in alterations of goal-directed and habitual behaviors.
Highlights
The dorsal striatum is a brain region involved in action control, with dorsomedial striatum (DMS) mediating goal-directed actions and dorsolateral striatum (DLS) mediating habitual actions
Using optogenetic targeting mechanisms to probe specific synapses for mu opioid receptors (MORs) plasticity and sensitivity to ethanol, we found that the only type of cortical input that expresses mOP-long-term synaptic depression (LTD) in DLS is the one originating in the anterior insular cortex (AIC)[5], and this mOP-LTD was sensitive to ethanol
We broadly showed that cortical inputs express mOP-LTD in the DLS and DMS5
Summary
The dorsal striatum is a brain region involved in action control, with dorsomedial striatum (DMS) mediating goal-directed actions and dorsolateral striatum (DLS) mediating habitual actions. We found that contrary to DLS, DMS mOP-LTD is induced by activation of MORs at inputs from both anterior cingulate and medial prefrontal cortices as well as at basolateral amygdala inputs and striatal cholinergic interneuron synapses on to DMS medium spiny neurons, suggesting that MOR synaptic plasticity in DMS is less synapse-specific than in DLS. Only mOP-LTD at cortical inputs was sensitive to alcohol’s deleterious effects These results suggest that alcohol-induced neuroadaptations are differentially expressed in a synapse-specific manner and could be playing a role in alterations of goal-directed and habitual behaviors. Using optogenetic targeting mechanisms to probe specific synapses for MOR plasticity and sensitivity to ethanol, we found that the only type of cortical input that expresses mOP-LTD in DLS is the one originating in the anterior insular cortex (AIC)[5], and this mOP-LTD was sensitive to ethanol. Similar to DLS, inputs from cortex, but not other inputs, were sensitive to the plasticity-ablating effects of ethanol
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