Dipsogenic Role of Angiotensin II during Fear Memory Retrieval

Motivational cues of thirst, sleep, and hunger impact memory and behavioral responses across species. Brain angiotensin II (AngII) is a potent thirst-producing peptide, where prior research demonstrated that angiotensin receptor blocker affects conditioned fear memory. We therefore hypothesized that acute water deprivation (WD) concurrent with angiotensin receptor blockage increases endogenous AngII levels and contributes to fear memory retrieval plasticity.C57BL/6J male mice underwent both auditory and contextual fear conditioning and received a single retrieval tone to initiate memory recall. During this time, mice were water restricted (24hrs) or ad-libitum in the presence/ absence of the angiotensin type1 receptor antagonist losartan (10mg/kg i.p.) given post fear memory retrieval. RT-qPCR, mass spectrometry, IHC, and ELISAs were performed to analyze specific synaptic plasticity and memory markers.Mice, which underwent WD during auditory memory retrieval, showed a significant reduction in freezing behavior in comparison to the non-WD controls during long-term memory (LTM) tests at 24hrs (p= 0.0019, n=12) and 1 week (p = 0.002, n=12). No difference in freezing response was observed in losartan-WD mice. Fear memory tests, after concurrent WD and contextual fear memory retrieval, showed no difference in freezing behavior between non-WD controls and WD with and without losartan (n=12). There was no significant difference in the baseline anxiety and locomotion behavior after water restriction. Following water deprivation, mass spectrometry revealed an elevated level of AngII peptide in the Subfornical region (SFO), an area essential for fluid regulation. The mRNA expression of RAS and synaptic plasticity genes - Agtr1, Agt and Bdnf (p<0.01, n=6) - were also significantly up-regulated only in WD saline mice. WD mice also had increased circulating aldosterone and angiotensin II (p<0.05, n=7) levels.Our findings indicate that elevated angiotensin II as a result of WD, reduced LTM, only during auditory fear memory reconsolidation, while altering the expression of specific RAS genes in SFO. Peripheral administration of losartan however blocked this effect. We propose that endogenous AngII as a dispogenic neuromodulator affects memory in a physiological state-dependent manner. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.