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Proc Natl Acad Sci U S A. 2017 Oct 10;114(41):E8750-E8759. doi: 10.1073/pnas.1707822114. Epub 2017 Sep 25.

Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration.

Author information

1
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260.
2
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA 15260.
3
Department of Neurobiology, University of Pittsburgh, Pittsburgh, PA 15260.
4
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
5
Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
6
Department of Psychiatry and Psychotherapy, University Medical Center, 37075 Göttingen, Germany.
7
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260; yandong@pitt.edu.

Abstract

The basolateral amygdala (BLA) sends excitatory projections to the nucleus accumbens (NAc) and regulates motivated behaviors partially by activating NAc medium spiny neurons (MSNs). Here, we characterized a feedforward inhibition circuit, through which BLA-evoked activation of NAc shell (NAcSh) MSNs was fine-tuned by GABAergic monosynaptic innervation from adjacent fast-spiking interneurons (FSIs). Specifically, BLA-to-NAcSh projections predominantly innervated NAcSh FSIs compared with MSNs and triggered action potentials in FSIs preceding BLA-mediated activation of MSNs. Due to these anatomical and temporal properties, activation of the BLA-to-NAcSh projection resulted in a rapid FSI-mediated inhibition of MSNs, timing-contingently dictating BLA-evoked activation of MSNs. Cocaine self-administration selectively and persistently up-regulated the presynaptic release probability of BLA-to-FSI synapses, entailing enhanced FSI-mediated feedforward inhibition of MSNs upon BLA activation. Experimentally enhancing the BLA-to-FSI transmission in vivo expedited the acquisition of cocaine self-administration. These results reveal a previously unidentified role of an FSI-embedded circuit in regulating NAc-based drug seeking and taking.

KEYWORDS:

basolateral amygdala; cocaine addiction; fast-spiking interneuron; medium spiny neuron; synaptic plasticity

PMID:
28973852
PMCID:
PMC5642706
DOI:
10.1073/pnas.1707822114
[Indexed for MEDLINE]
Free PMC Article

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