Depression and anxiety are prevalent psychiatric disorders affecting millions globally, with evidence suggesting that a significant proportion of individuals with anxiety will eventually develop depression. Despite extensive research, the mechanisms behind these disorders remain elusive, limiting treatment options and leaving many patients resistant to current therapies. One emerging theory suggests that reduced inhibition in the hippocampus and cortex, mediated by GABAergic inhibitory interneurons (INs), may contribute to major depressive disorder. This doctoral research seeks to uncover the mechanisms in a model of innate anxiolysis. By analyzing mRNA from hippocampal INs using cutting-edge sequencing technologies, the study will identify molecular changes in this model. Spatial transcriptomics will map these changes to specific IN subtypes, and local dendritic protein synthesis will be examined. Finally, viral techniques for genetic manipulation will explore the effects of key genes on stress responses and behavior. The results will shed light on how INs adapt to reduce anxiety, enhancing our understanding of the biological links between anxiety and depression and potentially guiding new treatment strategies.

Supervisor: Gali Umshweif-Nevo