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Neurons in the Organum Vasculosum of the Lamina Terminalis Sense Both Angiotensin II and NaCl to Regulate Thirst
Author(s) -
Kinsman Brian J.,
Browning Kirsteen N.,
Stocker Sean D.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.598.6
Subject(s) - subfornical organ , lamina terminalis , medicine , angiotensin ii , endocrinology , thirst , circumventricular organs , median preoptic nucleus , chemistry , homeostasis , angiotensin iii , osmoreceptor , lateral parabrachial nucleus , hypertonic saline , area postrema , hypothalamus , receptor , biology , angiotensin ii receptor type 1 , parabrachial nucleus
Angiotensin II (AngII) and NaCl are sensed by hypothalamic circumventricular organs to subsequently regulate body fluid homeostasis and blood pressure. AngII predominantly acts within the subfornical organ (SFO), whereas NaCl is sensed by neurons in the organum vasculosum of the lamina terminalis (OVLT). However, OVLT neurons also abundantly express AngII‐type I receptors. Therefore, we performed a series of in vitro and in vivo experiments in adult male Sprague‐Dawley rats to determine whether OVLT neurons sense both AngII and NaCl to impact body fluid homeostasis. First, in vitro whole‐cell recordings were performed on OVLT neurons in the presence of kynurenic acid (1mM) and bicuculline (20μM) to assess discharge responses to +7.5 mM NaCl (3 min) versus 100pM AngII (90s) in a randomized order. The majority of OVLT neurons (66%, 23/35) demonstrated an increase in discharge frequency to both AngII (1.31±0.25Hz to 2.19±0.31Hz; p<0.001) and hypertonic NaCl (1.11±0.18Hz to 2.16±0.27 Hz; p<0.001). Smaller proportions of OVLT neurons were either excited by NaCl alone (3/35), AngII alone (4/35), neither stimulus (3/35), or were inhibited by NaCl (2/35). In a second set of experiments, in vivo single‐unit recordings of OVLT neurons were performed to assess discharge responses to intracarotid injection (50uL over 15 s) of hypertonic NaCl (0.5M NaCl) or AngII (200ng). Half of OVLT neurons (50%, 6/12) displayed an increase in discharge to intracarotid injection of AngII (3.2±0.7 to 9.2±1.9 Hz, P<0.01) and 0.5M NaCl (3.6±0.6 to 9.0±1.6 Hz, P<0.01). The remainder of OVLT neurons showed an increase in discharge to hypertonic NaCl only (n=1) or AngII only (5/12). In a final set of experiments, we employed an optogenetic approach to determine the extent by which inhibition of OVLT neurons would attenuate thirst stimulated by NaCl versus AngII. rAAV2‐CamKII‐eNPHR3.0‐mCherry (5×10 12 particles/mL, 50nL) was injected into the OVLT, and an optical ferrule (200um OD) was implanted 300um dorsal to the injection site. Approximately 4 weeks later, optogenetic inhibition of OVLT neurons (561nm, 10mW) significantly reduced water intake in response to intravenous infusion (1.25 mL per 30 min) of 2M NaCl (control: 5.1±0.9 mL vs laser: 1.6±0.9 mL; n=4, P<0.01). In addition, optogenetic inhibition of OVLT neurons also attenuated hypotension‐induced thirst produced by intravenous injection of 25 mg/kg diazoxide (control: 4.5±0.8 mL vs laser: 1.3±0.7 mL; n=4, P<0.01). These findings suggest that individual OVLT neurons can sense both NaCl and AngII to functionally regulate thirst to both stimuli. Support or Funding Information NIH R01 HL113270 and AHA Established Investigator Award This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .