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      Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms

      research-article

      1 , 2 , 1 , 2 , 3 ,

      Journal of Neurophysiology

      American Physiological Society

      NPY, dopamine, VTA, GIRK

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          Abstract

          Neuropeptide-Y (NPY) has been shown to act on mesolimbic dopamine circuits to increase motivated behaviors toward food, but it is unclear exactly how NPY causes these responses. Here, we demonstrate that NPY directly inhibited a subset of ventral tegmental area (VTA) dopamine neurons through the activation of G protein-coupled inwardly rectifying potassium currents, and it inhibited both excitatory postsynaptic currents and inhibitory postsynaptic currents onto subsets of dopamine neurons through a presynaptic mechanism. Thus NPY uses multiple mechanisms to dynamically control VTA dopamine neuron activity.

          Abstract

          The mesocorticolimbic dopamine system, the brain’s reward system, regulates many different behaviors including food intake, food reward, and feeding-related behaviors, and there is increasing evidence that hypothalamic feeding-related neuropeptides alter dopamine neuron activity to affect feeding. For example, neuropeptide-Y (NPY), a strong orexigenic hypothalamic neuropeptide, increases motivation for food when injected into the ventral tegmental area (VTA). How NPY affects the activity of VTA dopamine neurons to regulate feeding behavior is unknown, however. In these studies we have used whole cell patch-clamp electrophysiology in acute brain slices from mice to examine how NPY affects VTA dopamine neuron activity. NPY activated an outward current that exhibited characteristics of a G protein-coupled inwardly rectifying potassium channel current in ~60% of dopamine neurons tested. In addition to its direct effects on VTA dopamine neurons, NPY also decreased the amplitude and increased paired-pulse ratios of evoked excitatory postsynaptic currents in a subset of dopamine neurons, suggesting that NPY decreases glutamatergic transmission through a presynaptic mechanism. Interestingly, NPY also strongly inhibited evoked inhibitory postsynaptic currents onto dopamine neurons by a presynaptic mechanism. Overall these studies demonstrate that NPY utilizes multiple mechanisms to affect VTA dopamine neuron activity, and they provide an important advancement in our understanding of how NPY acts in the VTA to control feeding behavior.

          NEW & NOTEWORTHY Neuropeptide-Y (NPY) has been shown to act on mesolimbic dopamine circuits to increase motivated behaviors toward food, but it is unclear exactly how NPY causes these responses. Here, we demonstrate that NPY directly inhibited a subset of ventral tegmental area (VTA) dopamine neurons through the activation of G protein-coupled inwardly rectifying potassium currents, and it inhibited both excitatory postsynaptic currents and inhibitory postsynaptic currents onto subsets of dopamine neurons through a presynaptic mechanism. Thus NPY uses multiple mechanisms to dynamically control VTA dopamine neuron activity.

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          Author and article information

          Journal
          J Neurophysiol
          J. Neurophysiol
          jn
          jn
          JN
          Journal of Neurophysiology
          American Physiological Society (Bethesda, MD )
          0022-3077
          1522-1598
          1 July 2017
          3 May 2017
          1 July 2018
          : 118
          : 1
          : 625-633
          Affiliations
          [1] 1Department of Biology, Georgia State University , Atlanta, Georgia;
          [2] 2The Neuroscience Institute, Georgia State University , Atlanta, Georgia; and
          [3] 3The Center for Obesity Reversal, Georgia State University , Atlanta, Georgia
          Author notes
          Address for reprint requests and other correspondence: A. G. Roseberry, Dept. of Biology, Georgia State Univ., 24 Peachtree Center Ave., Suite 430SA, Atlanta, GA 30303 (e-mail: aroseberry@ 123456gsu.edu ).
          Article
          PMC5511863 PMC5511863 5511863 JN-00879-2016 JN-00879-2016
          10.1152/jn.00879.2016
          5511863
          28469002
          7553b8f1-0afd-465c-80a0-2549b52173d0
          Copyright © 2017 the American Physiological Society
          Categories
          Research Article
          Cellular and Molecular Properties of Neurons

          NPY, dopamine, VTA, GIRK

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