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However, the source of the OTergic innervation, the cellular targets expressing the OT receptors (OTRs) and whether the PVN\u2010to\u2010CA2 OTergic system is altered during heart failure (HF), a condition recently associated with cognitive and mood decline, remains unknown. Using immunohistochemistry along with retrograde monosynaptic tracing, RNAscope and a novel OTR\u2010Cre rat line, we show that the PVN (but not the supraoptic nucleus) is an important source of OTergic innervation to the CA2. These OTergic fibers were found in many instances in close apposition to OTR expressing cells within the CA2. Interestingly, while only a small proportion of neurons were found to express OTRs (~15%), this expression was much more abundant in CA2 astrocytes (~40%), an even higher proportion that was recently reported for astrocytes in the central amygdala. Using an established ischemic rat heart failure (HF) model, we found that HF resulted in robust changes in the PVN\u2010to\u2010CA2 OTergic system, both at the source and target levels. Within the PVN, we found an increased OT immunoreactivity, along with a diminished OTR expression in PVN neurons. Within the CA2 of HF rats, we observed a blunted OTergic innervation, along with a diminished OTR expression, which appeared to be restricted to CA2 astrocytes. Taken together, our studies highlight astrocytes as key cellular targets mediating OTergic PVN inputs to the CA2 hippocampal region. Moreover, they provide the first evidence for an altered PVN\u2010to\u2010CA2 OTergic system in HF rats, which could potentially contribute to previously reported cognitive and mood impairments in this animal model.<\/jats:p>","DOI":"10.1111\/jne.13166","type":"journal-article","created":{"date-parts":[[2022,5,19]],"date-time":"2022-05-19T14:42:56Z","timestamp":1652971376000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Altered\n                    <scp>PVN\u2010to\u2010CA2<\/scp>\n                    hippocampal oxytocin pathway and reduced number of oxytocin\u2010receptor expressing astrocytes in heart failure rats"],"prefix":"10.1111","volume":"34","author":[{"given":"Ferdinand","family":"Althammer","sequence":"first","affiliation":[{"name":"Center for Neuroinflammation and Cardiometabolic Diseases Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ranjan K.","family":"Roy","sequence":"additional","affiliation":[{"name":"Center for Neuroinflammation and Cardiometabolic Diseases Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arthur","family":"Lefevre","sequence":"additional","affiliation":[{"name":"Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rami S.","family":"Najjar","sequence":"additional","affiliation":[{"name":"Department of Nutrition Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Schoenig","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Central Institute of Mental Health  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dusan","family":"Bartsch","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Central Institute of Mental Health  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Eliava","sequence":"additional","affiliation":[{"name":"Department of Neuropeptide Research in Psychiatry, Central Institute of Mental Health University of Heidelberg  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafaela G.","family":"Feresin","sequence":"additional","affiliation":[{"name":"Department of Nutrition Georgia State University  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7668-745X","authenticated-orcid":false,"given":"Elizabeth A. 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