Characterization of NPY Y2 receptor protein expression in the mouse brain. II. Coexistence with NPY, the Y1 receptor, and other neurotransmitter-related molecules.
ABSTRACT Neuropeptide Y (NPY) is widely expressed in the brain and its biological effects are mediated through a variety of receptors. We examined, using immunohistochemistry, expression of the Y2 receptor (R) protein in the adult mouse brain and its association with NPY and the Y1R, as well as a range of additional neurotransmitters and signaling-related molecules, which previously have not been defined. Our main focus was on the hippocampal formation (HiFo), amygdaloid complex, and hypothalamus, considering the known functions of NPY and the wide expression of NPY, Y1R, and Y2R in these regions. Y2R-like immunoreactivity (-LI) was distributed in nerve fibers/terminal endings throughout the brain axis, without apparent colocalization with NPY or the Y1R. Occasional coexistence between NPY- and Y1R-LI was found in the HiFo. Following colchicine treatment, Y2R-LI accumulated in cell bodies that coexpressed γ-aminobutyric acid (GABA) in a population of cells in the amygdaloid complex and lateral septal nucleus, but not in the HiFo. Instead, Y2R-positive nerve terminals appeared to surround GABA-immunoreactive (ir) cells in the HiFo and other neuronal populations, e.g., NPY-ir cells in HiFo and tyrosine hydroxylase-ir cells in the hypothalamus. In the HiFo, Y2R-ir mossy fibers coexpressed GABA, glutamic acid decarboxylase 67 and calbindin, and Y2R-LI was found in the same fibers that contained the presynaptic metabotropic glutamate receptor 2, but not together with any of the three vesicular glutamate transporters. Our findings provide further support that Y2R is mostly presynaptic, and that Y2Rs thus have a modulatory role in mediating presynaptic neurotransmitter release.
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Article: PYY3–36: Beyond food intake[Show abstract] [Hide abstract]
ABSTRACT: The gastrointestinal hormone peptide tyrosine tyrosine 3-36 (PYY3-36) has attained broad recognition with respect to its involvement in energy homeostasis and the control of food intake. It is mainly secreted by distal intestinal enteroendocrine L-cells in response to eating and exerts both neurally mediated paracrine and endocrine effects on various target organs. In addition to its gastrointestinal effects, PYY3-36 has long been known to inhibit food intake. Recent closer examination of the effects of PYY3-36 revealed that this gut-derived peptide also influences a wide spectrum of behavioral and cognitive functions that are pivotal for basic processes of perception and judgment, including central information processing, salience learning, working memory, and behavioral responding to novelty. Here, we review the effects of PYY3-36 that go beyond food intake and provide a conceptual framework suggesting that several apparently unrelated behavioral actions of PYY3-36 may actually reflect different manifestations of modulating the central dopamine system. Copyright © 2014. Published by Elsevier Inc.Frontiers in Neuroendocrinology 12/2014; DOI:10.1016/j.yfrne.2014.12.003 · 7.58 Impact Factor
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ABSTRACT: Sensory memory systems are modality-specific buffers that comprise information about external stimuli, which represent the earliest stage of information processing. While these systems are subject to cognitive neuroscience research for decades, little is known about the neurobiological basis of sensory memory. However, accumulating evidence suggests that the glutamatergic system and systems influencing glutamatergic neural transmission are important. In the current study we examine if functional promoter variations in neuropeptide Y (NPY) and its receptor gene NPY2R affect iconic memory processes using a partial report paradigm. We found that iconic memory decayed much faster in individuals carrying the rare promoter NPY2R G allele which is associated with increased expression of the Y2 receptor. Possibly this effect is due to altered presynaptic inhibition of glutamate release, known to be modulated by Y2 receptors. Altogether, our results provide evidence that the functionally relevant single nucleotide polymorphism (SNP) in the NPY2R promoter gene affect circumscribed processes of early sensory processing; i.e. only the stability of information in sensory memory buffers. This lead us to suggest that especially the stability of information in sensory memory buffers depends on glutamatergic neural transmission and factors modulating glutamatergic turnover.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 08/2014; 24(8). DOI:10.1016/j.euroneuro.2014.03.003 · 5.40 Impact Factor
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ABSTRACT: A large literature has demonstrated that neuropeptide Y (NPY) regulates many emotional and reward-related behaviors via its primary receptors, Y1R and Y2R. Classically, NPY actions at postsynaptic Y1R decrease anxiety, depression, and alcohol drinking, while its actions at presynaptic Y2R produce the opposite behavioral phenotypes. However, emerging evidence suggests that activation of Y2R can also produce anxiolysis in a brain region and neurotransmitter system-dependent fashion. Further, numerous human and rodent studies have reported that females display higher levels of anxiety, depression, and alcohol drinking. In this study, we evaluated sex differences and the role of Y2R on GABAergic transmission in these behaviors using a novel transgenic mouse that lacks Y2R specifically in VGAT-expressing neurons (VGAT-Y2R knockout). First, we confirmed our genetic manipulation by demonstrating that Y2R protein expression was decreased and that a Y2R agonist could not alter GABAergic transmission in the extended amygdala, a limbic brain region critically implicated in the regulation of anxiety and alcohol drinking behaviors, using immunofluorescence and slice electrophysiology. Then, we tested male and female VGAT-Y2R knockout mice on a series of behavioral assays for anxiety, depression, fear, anhedonia, and alcohol drinking. We found that females displayed greater basal anxiety, higher levels of ethanol consumption, and faster fear conditioning than males, and that knockout mice exhibited enhanced depressive-like behavior in the forced swim test. Together, these results confirm previous studies that demonstrate higher expression of negative affective and alcohol drinking behaviors in females than males, and they highlight the importance of Y2R function in GABAergic systems in the expression of depressive-like behavior.Frontiers in Integrative Neuroscience 12/2013; 7:100. DOI:10.3389/fnint.2013.00100