title: Hypothalamic Vasopressinergic Projections Innervate Central Amygdala GABAergic Neurons: Implications for Anxiety and Stress Coping.
abstract: The arginine-vasopressin (AVP)-containing hypothalamic magnocellular neurosecretory neurons (VPMNNs) are known for their role in hydro-electrolytic balance control via their projections to the neurohypophysis. Recently, projections from these same neurons to hippocampus, habenula and other brain regions in which vasopressin infusion modulates contingent social and emotionally-affected behaviors, have been reported. Here, we present evidence that VPMNN collaterals also project to the amygdaloid complex, and establish synaptic connections with neurons in central amygdala (CeA). The density of AVP innervation in amygdala was substantially increased in adult rats that had experienced neonatal maternal separation (MS), consistent with our previous observations that MS enhances VPMNN number in the paraventricular (PVN) and supraoptic (SON) nuclei of the hypothalamus. In the CeA, V1a AVP receptor mRNA was only observed in GABAergic neurons, demonstrated by complete co-localization of V1a transcripts in neurons expressing Gad1 and Gad2 transcripts in CeA using the RNAscope method. V1b and V2 receptor mRNAs were not detected, using the same method. Water-deprivation (WD) for 24 h, which increased the metabolic activity of VPMNNs, also increased anxiety-like behavior measured using the elevated plus maze (EPM) test, and this effect was mimicked by bilateral microinfusion of AVP into the CeA. Anxious behavior induced by either WD or AVP infusion was reversed by CeA infusion of V1a antagonist. VPMNNs are thus a newly discovered source of CeA inhibitory circuit modulation, through which both early-life and adult stress coping signals are conveyed from the hypothalamus to the amygdala.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México Mexico City, Mexico.
authors.forename: Vito S
authors.initials: VS
authors.lastname: Hernández
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México Mexico City, Mexico.
authors.forename: Oscar R
authors.initials: OR
authors.lastname: Hernández
authors.affiliation: División de Neurociencias, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México Mexico City, Mexico.
authors.forename: Miguel
authors.initials: M
authors.lastname: Perez de la Mora
authors.affiliation: Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México Mexico City, Mexico.
authors.forename: María J
authors.initials: MJ
authors.lastname: Gómora
authors.affiliation: Department of Neuroscience, Karolinska Institutet Stockholm, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Fuxe
authors.affiliation: Section on Molecular Neuroscience, National Institute of Mental Health, National Institutes of Health (NIH) Bethesda, MD, USA.
authors.forename: Lee E
authors.initials: LE
authors.lastname: Eiden
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Nacional Autónoma de México Mexico City, Mexico.
authors.forename: Limei
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced / Q000378:metabolism*; D001127:Arginine Vasopressin / Q000378:metabolism*; D001522:Behavior, Animal; D066274:Central Amygdaloid Nucleus / Q000166:cytology / Q000378:metabolism; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000166:cytology / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism; D008297:Male; D008426:Maternal Deprivation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D017208:Rats, Wistar; D017483:Receptors, Vasopressin / Q000378:metabolism*; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism; D014868:Water Deprivation
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D017483:Receptors, Vasopressin; C582098:V1a vasopressin receptor, rat; D001127:Arginine Vasopressin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; C401141:glutamate decarboxylase 2
keywords: Gad1; Gad2; RNAscope; V1a; magnocellular; maternal separation; microinjection; synapses