title: Structure and function of the amygdaloid NPY system: NPY Y2 receptors regulate excitatory and inhibitory synaptic transmission in the centromedial amygdala.
abstract: The amygdala is essential for generating emotional-affective behaviors. It consists of several nuclei with highly selective, elaborate functions. In particular, the central extended amygdala, consisting of the central amygdala (CEA) and the bed nucleus of the stria terminalis (BNST) is an essential component actively controlling efferent connections to downstream effectors like hypothalamus and brain stem. Both, CEA and BNST contain high amounts of different neuropeptides that significantly contribute to synaptic transmission. Among these, neuropeptide Y (NPY) has emerged as an important anxiolytic and fear-reducing neuromodulator. Here, we characterized the expression, connectivity and electrophysiological function of NPY and Y2 receptors within the CEA. We identified several NPY-expressing neuronal populations, including somatostatin- and calretinin-expressing neurons. Furthermore, in the main intercalated nucleus, NPY is expressed primarily in dopamine D1 receptor-expressing neurons but also in interspersed somatostatin-expressing neurons. Interestingly, NPY neurons did not co-localize with the Y2 receptor. Retrograde tract tracing experiments revealed that NPY neurons reciprocally connect the CEA and BNST. Functionally, the Y2 receptor agonist PYY3-36, reduced both, inhibitory as well as excitatory synaptic transmission in the centromedial amygdala (CEm). However, we also provide evidence that lack of NPY or Y2 receptors results in increased GABA release specifically at inhibitory synapses in the CEm. Taken together, our findings suggest that NPY expressed by distinct populations of neurons can modulate afferent and efferent projections of the CEA via presynaptic Y2 receptors located at inhibitory and excitatory synapses.
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1a, 6020, Innsbruck, Austria.
authors.forename: J
authors.initials: J
authors.lastname: Wood
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1a, 6020, Innsbruck, Austria.|Institute of Physiology I (Neurophysiology), Westfälische Wilhelms-Universität, Munster, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Verma
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1a, 6020, Innsbruck, Austria.|Capes Foundation, Ministry of Education of Brazil, Brasília, DF, 70040-020, Brazil.
authors.forename: G
authors.initials: G
authors.lastname: Lach
authors.affiliation: Janssen Research & Development, LLC, San Diego, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Bonaventure
authors.affiliation: Neuroscience Division, Garvan Institute of Medical Research, Darlinghurst, Sydney, NSW, 2010, Australia.
authors.forename: H
authors.initials: H
authors.lastname: Herzog
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1a, 6020, Innsbruck, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Sperk
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Peter-Mayr-Strasse 1a, 6020, Innsbruck, Austria. ramon.tasan@i-med.ac.at.
authors.forename: R O
authors.initials: RO
authors.lastname: Tasan
mesh_terms: D000679:Amygdala / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D064032:Calbindin 2 / Q000378:metabolism; D066274:Central Amygdaloid Nucleus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D053444:Inhibitory Postsynaptic Potentials; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D012686:Septal Nuclei / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D013004:Somatostatin / Q000378:metabolism
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D013004:Somatostatin
keywords: Central amygdala; Dopamine D1 receptor; Intercalated neurons; NPY; Neuropeptide Y; Y2 receptor