Astrocytes, once considered passive support cells in the central nervous system, are now recognized as key modulators of synaptic plasticity and emotional behaviors. Recent studies highlight their significant involvement in anxiety- and depressive-like behaviors, particularly through astrocytic oxytocin (OXT) signaling. While the specific contributions of astrocytes remain largely unexplored, research has extensively characterized the role of OXT in regulating social behavior, particularly in the lateral septum (LS). OXT protective effects against social fear, as seen in animal models of social anxiety disorder (SAD), one of the most prevalent anxiety disorders, underscore its therapeutic potential. Social interactions are vital for the survival and well-being of individual. However, when responses to social cues become maladaptive, as in SAD, it poses a pathological challenge. Given the high prevalence of SAD and the limited efficacy of current treatments, there is an urgent need for a deeper exploration of these underlying mechanisms. To better understand the neuronal and molecular mechanisms underlying SAD, the social fear conditioning (SFC) paradigm has been developed. In this paradigm, social fear is induced through operant conditioning, leading to avoidance of social stimuli, followed by repeated social exposure, which mirrors cognitive behavioral therapy (CBT) in humans. Research using the SFC paradigm has demonstrated that OXT signaling reverses social fear in mice. Moreover, alterations in OXTR binding in the LS during repeated exposure to social cues suggest that OXTR-mediated signaling plays a key role in both the expression and extinction of social fear. Given the limited treatment options for SAD and the growing evidence of astrocytes involvement in modulating emotional behaviors through OXT signaling further exploration of astrocytic mechanisms is urgently needed. Investigating astrocytic OXT signaling could reveal new insights into the regulation of social behaviors and identify novel therapeutic targets for anxiety disorders like SAD. In this thesis, I demonstrated the involvement of astrocytes in the learning processes associated with social fear acquisition and their subsequent influence on social behaviors. Additionally, I identified a potential role for astrocytic OXT signaling in modulating social behaviors during the extinction phase of fear responses, although this signaling did not appear to impact the initial acquisition of social fear itself. To account for possible sex differences in responses, both male and female mice were included to characterize the distinct effects observed.
Laura Boi (Thu,) studied this question.