title: Cell-specific retrograde signals mediate antiparallel effects of angiotensin II on osmoreceptor afferents to vasopressin and oxytocin neurons.
abstract: Homeostatic control of extracellular fluid osmolality in rats requires a parallel excitation of vasopressin (VP) and oxytocin (OT) neurosecretory neurons by osmoreceptor afferents to regulate the amount of water and sodium in the urine under normal conditions. However, during decreased blood volume (hypovolemia), natriuresis is suppressed, whereas osmotically driven antidiuresis is enhanced to promote retention of isotonic fluid. Because Angiotensin II (Ang II) is released centrally to indicate hypovolemia, we hypothesized that Ang II can evoke a state-dependent switch in circuit function. Here, we show that Ang II, a neuropeptide released centrally during hypovolemia, suppresses osmoreceptor-mediated synaptic excitation of OT neurons while potentiating excitation of VP neurons. Ang II does this by inducing cell-autonomous release of nitric oxide by VP neurons and endocannabinoids by OT neurons to respectively enhance and reduce glutamate release by osmoreceptor afferents. These findings indicate that peptide modulators such as Ang II can regulate synaptic communication to achieve a state-dependent and target-specific modulation of circuit activity.
authors.affiliation: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, QC H3G1A4, Canada; Discovery Neuroscience, F. Hoffman-La Roche AG, Basel 4051, Switzerland.
authors.forename: Tevye J
authors.initials: TJ
authors.lastname: Stachniak
authors.affiliation: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, QC H3G1A4, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Trudel
authors.affiliation: Centre for Research in Neuroscience, Research Institute of the McGill University Health Centre, Montreal, QC H3G1A4, Canada. Electronic address: charles.bourque@mcgill.ca.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D063388:Endocannabinoids / Q000378:metabolism; D005260:Female; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009994:Osmolar Concentration; D064587:Osmoregulation; D010121:Oxytocin / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017208:Rats, Wistar; D011984:Sensory Receptor Cells / Q000378:metabolism* / Q000502:physiology; D013569:Synapses / Q000378:metabolism / Q000502:physiology; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D063388:Endocannabinoids; D014667:Vasopressins; D000804:Angiotensin II; D009569:Nitric Oxide; D010121:Oxytocin