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Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms.
J Neurophysiol. 2017 07 01; 118(1):625-633.JN

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.

Authors+Show Affiliations

Department of Biology, Georgia State University, Atlanta, Georgia. The Neuroscience Institute, Georgia State University, Atlanta, Georgia; and.Department of Biology, Georgia State University, Atlanta, Georgia; aroseberry@gsu.edu. The Neuroscience Institute, Georgia State University, Atlanta, Georgia; and. The Center for Obesity Reversal, Georgia State University, Atlanta, Georgia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28469002

Citation

West, Katherine Stuhrman, and Aaron G. Roseberry. "Neuropeptide-Y Alters VTA Dopamine Neuron Activity Through Both Pre- and Postsynaptic Mechanisms." Journal of Neurophysiology, vol. 118, no. 1, 2017, pp. 625-633.
West KS, Roseberry AG. Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms. J Neurophysiol. 2017;118(1):625-633.
West, K. S., & Roseberry, A. G. (2017). Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms. Journal of Neurophysiology, 118(1), 625-633. https://doi.org/10.1152/jn.00879.2016
West KS, Roseberry AG. Neuropeptide-Y Alters VTA Dopamine Neuron Activity Through Both Pre- and Postsynaptic Mechanisms. J Neurophysiol. 2017 07 1;118(1):625-633. PubMed PMID: 28469002.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuropeptide-Y alters VTA dopamine neuron activity through both pre- and postsynaptic mechanisms. AU - West,Katherine Stuhrman, AU - Roseberry,Aaron G, Y1 - 2017/05/03/ PY - 2016/11/14/received PY - 2017/04/27/revised PY - 2017/04/27/accepted PY - 2017/5/5/pubmed PY - 2018/4/12/medline PY - 2017/5/5/entrez KW - GIRK KW - NPY KW - VTA KW - dopamine SP - 625 EP - 633 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 118 IS - 1 N2 - 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. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/28469002/Neuropeptide_Y_alters_VTA_dopamine_neuron_activity_through_both_pre__and_postsynaptic_mechanisms_ L2 - http://www.physiology.org/doi/full/10.1152/jn.00879.2016?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -