Social Buffering of Stress-Induced Changes in the Paraventricular Nucleus of the Hypothalamus

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dc.contributor.advisorBains, Jaideep S.
dc.contributor.authorLoewen, Spencer P.
dc.contributor.committeememberHill, Matthew N.
dc.contributor.committeememberThompson, Roger J.
dc.contributor.committeememberTeskey, G. Campbell
dc.contributor.committeememberChristianson, John P.
dc.dateFall Convocation
dc.date.accessioned2023-05-11T05:57:19Z
dc.date.embargolift2024-06-28
dc.date.issued2022-06-28
dc.description.abstractSocial species, by definition, utilize social interactions with others that are essential for survival and reproductive success. Social interactions can mitigate the harmful effects of stress through a process known as social buffering. Our understanding of the cellular mechanisms that underlie social buffering, however, is poor. Acute stress primes glutamate synapses onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus (CRHPVN neurons), resulting in stress-induced metaplasticity. This priming of synapses, which manifests as short-term potentiation (STP) of excitatory transmission elicited by high-frequency afferent stimulation, is buffered in female but not male mice by the presence of a naive partner. The cellular substrates underlying this sex-specific buffering of these synaptic changes have not been elucidated. Increasing evidence suggests that neurons in the PVN are sensitive to neuromodulation by locally released substances. Here, I tested the hypothesis that local vasopressin (VP) signaling in the PVN contributes to social buffering of synaptic metaplasticity in females. I used whole-cell patch clamp recordings from CRHPVN neurons to examine the effects of VP on STP in these cells. I found that selective pharmacological blockade of VP 1a receptors prevented social buffering of STP. Conversely, exogenous VP mimicked the effects of social buffering and reduced STP in CRHPVN neurons from single-housed stressed females but had no effect in males. These synaptic actions rely on direct VP signaling on CRHPVN neurons that reduce the AMPA/NMDA ratio. In addition, I extended the effects of social buffering to cognitive functions and examined how changes in CRHPVN neuron activity influence memory retrieval. I found that social buffering improves stress-induced impairments in long-term memory retrieval in female mice, but not in males. Furthermore, optogenetic silencing of CRHPVN neurons in single-housed stressed female mice reduced STP and replicated the social buffering effect by improving memory retrieval after stress. Collectively, the work in this thesis contributes to our understanding of the mechanism that underlies sex-specific social buffering of STP and provides evidence that the effects of social buffering may be determined by changes in CRHPVN neuron activity.
dc.identifier.citationLoewen, S. P. (2022). Social Buffering of Stress-Induced Changes in the Paraventricular Nucleus of the Hypothalamus (Doctoral thesis). University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca .
dc.identifier.urihttp://hdl.handle.net/1880/116472
dc.identifier.urihttps://dx.doi.org/10.11575/PRISM/dspace/41316
dc.language.isoEnglish
dc.publisher.facultyCumming School of Medicine
dc.subjectCRH
dc.subjectstress
dc.subjecthypothalamus
dc.subjectPVN
dc.subjectsocial buffering
dc.subjectsynapse
dc.subjectvasopressin
dc.subjectelectrophysiology
dc.subject.classificationBiology--Neuroscience
dc.subject.classificationBiology--Physiology
dc.titleSocial Buffering of Stress-Induced Changes in the Paraventricular Nucleus of the Hypothalamus
dc.typedoctoral thesis
thesis.degree.disciplineMedicine – Neuroscience
thesis.degree.grantorUniversity of Calgary
thesis.degree.nameDoctor of Philosophy (PhD)
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