Identifying ‘angiotensin sensitive’ neurons in the lamina terminalis that coordinate endocrine, cardiovascular and behavioral responses mediating body fluid homeostasis

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Body fluid homeostasis is controlled by endocrine, cardiovascular and behavioral responses that maintain blood osmolality and perfusion pressure at optimal levels. Angiotensin type 1a receptors (AT1a) in the brain are known to coordinate these responses but the underlying neuronal circuits remain unclear. This study investigates the structure and function of AT1a neurons in the median preoptic nucleus (MnPO) and the organum vasculosum of the lamina terminalis (OVLT) to better understand their role in body fluid homeostasis. Using male mice that express Cre‐recombinase prior to the STOP codon of the AT1a gene (i.e., AT1a‐Cre mice), initial studies combined genetic reporting with in situ hybridization to reveal that neurons in the MnPO and OVLT that express AT1a are largely glutamatergic. Subsequently, AT1a‐Cre mice were delivered a Cre‐inducible adeno‐associated virus to induce expression of channelrhodopsin‐2 (ChR2) and enhanced yellow fluorescent protein (eYFP) specifically within AT1a neurons of the MnPO/OVLT. Neuroanatomical and in vitro electrophysiological studies revealed that AT1a neurons in the MnPO/OVLT send dense glutamatergic projections into the paraventricular nucleus of the hypothalamus that synapse onto vasopressin (AVP)‐synthesizing neurons. To evaluate the functionality of this connection, we optogenetically stimulated AT1a‐expressing neurons in the MnPO/OVLT and recorded cardiovascular parameters in anesthetized mice. Relative to control mice given virus that only expressed eYFP, 10 min of optogenetic stimulation robustly elevated systolic blood pressure in mice expressing ChR2. This effect was rapid in its onset (34 ± 9 vs. −2 ± 4 mmHg at 5 min, p < 0.05) but persisted for the entire 50 min of cardiovascular recording (45 ± 11 vs. −3 ± 7 mmHg at 50 min, p < 0.05). Intriguingly, optogenetic stimulation elicited a significant increase in Fos induction in AVP neurons within the PVN relative to controls. To evaluate behavioral responses, AT1a neurons in the MnPO/OVLT were optogenetically stimulated while conscious freely moving mice had access to both water and 0.3M NaCl. Relative to controls, mice delivered ChR2 showed a significant increase in both water and sodium consumption. Collectively, the results suggest that AT1a neurons in the MnPO/OVLT comprise a neuronal circuit that mediates endocrine, cardiovascular and behavioral responses that maintain body fluid homeostasis.Support or Funding InformationNIH: HL122494 (EGK), MH104641(CJF), HL125805 and AHA GRNT33660969 (AdK)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.