title: Switching control of sympathetic activity from forebrain to hindbrain in chronic dehydration.
abstract: We investigated the mechanisms responsible for increased blood pressure and sympathetic nerve activity (SNA) caused by 2-3 days dehydration (DH) both in vivo and in situ preparations. In euhydrated (EH) rats, systemic application of the AT(1) receptor antagonist Losartan and subsequent pre-collicular transection (to remove the hypothalamus) significantly reduced thoracic (t)SNA. In contrast, in DH rats, Losartan, followed by pre-collicular and pontine transections, failed to reduce tSNA, whereas transection at the medulla-spinal cord junction massively reduced tSNA. In DH but not EH rats, selective inhibition of the commissural nucleus tractus solitarii (cNTS) significantly reduced tSNA. Comparable data were obtained in both in situ and in vivo (anaesthetized/conscious) rats and suggest that following chronic dehydration, the control of tSNA transfers from supra-brainstem structures (e.g. hypothalamus) to the medulla oblongata, particularly the cNTS. As microarray analysis revealed up-regulation of AP1 transcription factor JunD in the dehydrated cNTS, we tested the hypothesis that AP1 transcription factor activity is responsible for dehydration-induced functional plasticity. When AP1 activity was blocked in the cNTS using a viral vector expressing a dominant negative FosB, cNTS inactivation was ineffective. However, tSNA was decreased after pre-collicular transection, a response similar to that seen in EH rats. Thus, the dehydration-induced switch in control of tSNA from hypothalamus to cNTS seems to be mediated via activation of AP1 transcription factors in the cNTS. If AP1 activity is blocked in the cNTS during dehydration, sympathetic activity control reverts back to forebrain regions. This unique reciprocating neural structure-switching plasticity between brain centres emphasizes the multiple mechanisms available for the adaptive response to dehydration.
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, UK.
authors.forename: Débora S A
authors.initials: DS
authors.lastname: Colombari
authors.forename: Eduardo
authors.initials: E
authors.lastname: Colombari
authors.forename: Andre H
authors.initials: AH
authors.lastname: Freiria-Oliveira
authors.forename: Vagner R
authors.initials: VR
authors.lastname: Antunes
authors.forename: Song T
authors.initials: ST
authors.lastname: Yao
authors.forename: Charles
authors.initials: C
authors.lastname: Hindmarch
authors.forename: Alastair V
authors.initials: AV
authors.lastname: Ferguson
authors.forename: Mark
authors.initials: M
authors.lastname: Fry
authors.forename: David
authors.initials: D
authors.lastname: Murphy
authors.forename: Julian F R
authors.initials: JF
authors.lastname: Paton
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D002908:Chronic Disease; D003681:Dehydration / Q000503:physiopathology*; D007031:Hypothalamus / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D023421:Models, Animal; D009473:Neuronal Plasticity / Q000502:physiology; D016548:Prosencephalon / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012249:Rhombencephalon / Q000502:physiology*; D017552:Solitary Nucleus / Q000502:physiology; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D000959:Antihypertensive Agents; D019808:Losartan