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Publication : High-Frequency Activation of Nucleus Accumbens D1-MSNs Drives Excitatory Potentiation on D2-MSNs.

First Author  Francis TC Year  2019
Journal  Neuron Volume  103
Issue  3 Pages  432-444.e3
PubMed ID  31221559 Mgi Jnum  J:283548
Mgi Id  MGI:6355715 Doi  10.1016/j.neuron.2019.05.031
Citation  Francis TC, et al. (2019) High-Frequency Activation of Nucleus Accumbens D1-MSNs Drives Excitatory Potentiation on D2-MSNs. Neuron 103(3):432-444.e3
abstractText  Subtypes of nucleus accumbens medium spiny neurons (MSNs) promote dichotomous outcomes in motivated behaviors. However, recent reports indicate enhancing activity of either nucleus accumbens (NAc) core MSN subtype augments reward, suggesting coincident MSN activity may underlie this outcome. Here, we report a collateral excitation mechanism in which high-frequency, NAc core dopamine 1 (D1)-MSN activation causes long-lasting potentiation of excitatory transmission (LLP) on dopamine receptor 2 (D2)-MSNs. Our mechanistic investigation demonstrates that this form of plasticity requires release of the excitatory peptide substance P from D1-MSNs and robust cholinergic interneuron activation through neurokinin receptor stimulation. We also reveal that D2-MSN LLP requires muscarinic 1 receptor activation, intracellular calcium signaling, and GluR2-lacking AMPAR insertion. This study uncovers a mechanism for shaping NAc core activity through the transfer of excitatory information from D1-MSNs to D2-MSNs and may provide a means for altering goal-directed behavior through coordinated MSN activity.
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