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      Functional consequences of neuropeptide and small-molecule co-transmission

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      Nature Reviews Neuroscience
      Springer Nature

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          Abstract

          Small-molecule–neuropeptide co-transmission is pervasive throughout the nervous system of all animals. In this Review, Nusbaum, Blitz and Marder discuss how co-transmission is an important source for the considerable flexibility that has been established for synapses, circuits and behaviour.

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          Most cited references94

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          Neuropeptide transmission in brain circuits.

          Neuropeptides are found in many mammalian CNS neurons where they play key roles in modulating neuronal activity. In contrast to amino acid transmitter release at the synapse, neuropeptide release is not restricted to the synaptic specialization, and after release, a neuropeptide may diffuse some distance to exert its action through a G protein-coupled receptor. Some neuropeptides such as hypocretin/orexin are synthesized only in single regions of the brain, and the neurons releasing these peptides probably have similar functional roles. Other peptides such as neuropeptide Y (NPY) are synthesized throughout the brain, and neurons that synthesize the peptide in one region have no anatomical or functional connection with NPY neurons in other brain regions. Here, I review converging data revealing a complex interaction between slow-acting neuromodulator peptides and fast-acting amino acid transmitters in the control of energy homeostasis, drug addiction, mood and motivation, sleep-wake states, and neuroendocrine regulation. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Antagonism of central melanocortin receptors in vitro and in vivo by agouti-related protein.

            Expression of Agouti protein is normally limited to the skin where it affects pigmentation, but ubiquitous expression causes obesity. An expressed sequence tag was identified that encodes Agouti-related protein, whose RNA is normally expressed in the hypothalamus and whose levels were increased eightfold in ob/ob mice. Recombinant Agouti-related protein was a potent, selective antagonist of Mc3r and Mc4r, melanocortin receptor subtypes implicated in weight regulation. Ubiquitous expression of human AGRP complementary DNA in transgenic mice caused obesity without altering pigmentation. Thus, Agouti-related protein is a neuropeptide implicated in the normal control of body weight downstream of leptin signaling.
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              Drosophila neuropeptides in regulation of physiology and behavior.

              Studies of neuropeptide and peptide hormone signaling are coming of age in Drosophila due to rapid developments in molecular genetics approaches that overcome the difficulties caused by the small size of the fly. In addition we have genome-wide information on genes involved in peptide signaling, and growing pools of peptidomics data. A large number of different neuropeptides has been identified in a huge variety of neuron types in different parts of the Drosophila nervous system and cells in other locations. This review addresses questions related to peptidergic signaling in the Drosophila nervous system, especially how peptides regulate physiology and behavior during development and in the mature fly. We first summarize novel findings on neuropeptide precursor genes, processed bioactive peptides and their cognate receptors. Thereafter we provide an overview of the physiological and behavioral roles of peptide signaling in Drosophila. These roles include regulation of development, growth, feeding, metabolism, reproduction, homeostasis, and longevity, as well as neuromodulation in learning and memory, olfaction and locomotor control. The substrate of this signaling is the peptide products of about 42 precursor genes expressed in different combinations in a variety of neuronal circuits or that act as circulating hormones. Approximately 45 G-protein-coupled peptide receptors are known in Drosophila and for most of these the ligands have been identified. Functions of some peptides are better understood than others, and much work remains to reveal the spectrum of roles neuropeptides and peptide hormones play in the daily life of a fly. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Nature Reviews Neuroscience
                Nat Rev Neurosci
                Springer Nature
                1471-003X
                1471-0048
                June 8 2017
                June 8 2017
                :
                :
                Article
                10.1038/nrn.2017.56
                5547741
                28592905
                c1017749-4fb5-49c2-bbb4-f7065086666b
                © 2017
                History

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