@article{77573e5c184542e38fb09e7db16a028b,
title = "Pathway- and Cell-Specific Kappa-Opioid Receptor Modulation of Excitation-Inhibition Balance Differentially Gates D1 and D2 Accumbens Neuron Activity",
abstract = "Endogenous dynorphin signaling via the kappa-opioid receptor (KOR) in the nucleus accumbens (NAcc) powerfully mediates negative affective states and stress reactivity. Excitatory inputs from the hippocampus and amygdala play a fundamental role in shaping the activity of both NAcc D1 and D2 MSNs, which encode positive and negative motivational valences, respectively. However, a circuit-based mechanism by which KOR modulation of excitation-inhibition balance modifies D1 and D2 MSN activity is lacking. Here, we provide a comprehensive synaptic framework wherein presynaptic KOR inhibition decreases the excitatory drive of D1 MSN activity by the amygdala, but not the hippocampus. Conversely, presynaptic inhibition by KORs of inhibitory synapses on D2 MSNs enhances integration of excitatory drive by the amygdala and hippocampus. In conclusion, we describe a circuit-based mechanism showing differential gating of afferent control of D1 and D2 MSN activity by KORs in a pathway-specific manner.",
keywords = "GABA, amygdala, dynorphin, electrophysiology, glutamate, hippocampus, hypothalamus",
author = "Tejeda, {Hugo A.} and Jocelyn Wu and Kornspun, {Alana R.} and Marco Pignatelli and Vadim Kashtelyan and Krashes, {Michael J.} and Lowell, {Brad B.} and Carlezon, {William A.} and Antonello Bonci",
note = "Funding Information: We thank members of the Bonci laboratory, Drs. Alex Hoffman, Carl Lupica, and Roy Wise, for helpful discussions. We thank Drs. Yeka Aponte and Zheng-Xiong Xi for sharing equipment. We thank Dr. Marisela Morales for reagents, resources, and guidance on FG and radioactive in situ hybridization experiments. We thank Drs. Carlos Mejias-Aponte, Bing Liu, and Hui-Ling Wang for assistance with FG and radioactive in situ hybridization experiments. We thanks Drs. Robert Steiner and Sasha Kauffman for generously providing KOR cDNA. We thank Drs. Bruce Cohen, Anita Bechtholt, and Ashlee Van't Veer for their roles in developing KOR-floxed mice. This work was funded by the NIDA Intramural Research Program and grants to B.B.L. from the NIH and NIDDK (R01 DK096010, R01 DK089044, R01 DK071051, and R01 DK075632). Publisher Copyright: {\textcopyright} 2017",
year = "2017",
month = jan,
day = "4",
doi = "10.1016/j.neuron.2016.12.005",
language = "English",
volume = "93",
pages = "147--163",
journal = "Neuron",
issn = "0896-6273",
number = "1",
}