In susceptible individuals, episodic memories of overwhelmingly stressful experiences can give rise to debilitating socio-affective symptoms, including social dysfunction. This occurs even when such memories are not easily accessed for retrieval. In this case, it is generally accepted that the restricted retrieval of such memories is due to their having been encoded with state-dependent processes. This means that the memories can best be retrieved if the brain states at memory encoding and retrieval are similar. Recently, we demonstrated that when inhibitory receptors in the hippocampus are activated, it changes the way stressful events are encoded and can promote the formation of state-dependent stress-related memories. However, the mechanisms which mediate their state-dependent processing and those which link stress-related memories to social dysfunction are not well understood. Here, using behavioral and pharmacological approaches in mice, we demonstrate that the hippocampus is a brain region which mediates state-dependent stress-related memories and show that a specific group of inhibitory receptors are responsible for their restricted encoding and retrieval. Using network recording approaches, we found that while these receptors are activated, the information flow from hippocampal to cortical circuits is changed. We next show that such memories can disrupt social behavior, and that this effect is likely due to the changed pattern of hippocampal activity during social interaction. Together, our data suggest that disrupted patterning of hippocampal activity underlies stress-related memory-induced social deficits. Lastly, we identify two distinct hippocampal targets, a cellular population and a neural circuit, for improving the social dysfunction which follows stress-related state-dependent memories.

Creator

• Meyer, Mariah Alexie Azuz

DOI

• https://doi.org/10.21985/n2-9hkp-sc13

Subject

• Neurosciences

Language

• en

Alternate Identifier

• etdadmin_upload_718313
• http://dissertations.umi.com/northwestern:14995

Keyword

• Chemogenetics
• Hippocampus
• Stress
• Dentate gyrus
• Social behavior
• Oxytocin

Date created

• 2020-01-01

Resource type

• Dissertation

Rights statement

• In Copyright