Inhibitory synapse diversity in the centromedial amygdala anxiety circuitry

• Applicant: Professorin Dr. Dilja Krueger-Burg
• Subject Area: Biological Psychiatry ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 440804067

Abnormalities in inhibitory synaptic transmission are intricately linked to the pathophysiology of psychiatric disorders, but the underlying mechanisms are poorly understood. While synaptic inhibition is crucial throughout the brain, a number of key nodes exist that are particularly heavily controlled by inhibitory inputs, and one of these is the centromedial amygdala (CeM). The CeM represents the major output nucleus of the amygdala complex, through which anxiety responses and other psychiatrically relevant behaviors are processed. CeM neurons receive numerous inhibitory inputs from both afferent projections and local interneurons, which play a pivotal role in gating CeM projections and hence amygdala output. Understanding the biology of these synapses is therefore essential in evaluating their vulnerability to pathogenic mutations and their potential as therapeutic targets. To date, however, virtually nothing is known about the molecules that govern the assembly and function of CeM inhibitory synapses, largely due to a fundamental lack of knowledge on the composition and heterogeneity of the inhibitory postsynaptic proteome throughout the brain. The current proposal aims to fill this critical knowledge gap by addressing two key questions: First, what is the molecular and functional architecture of CeM inhibitory postsynapses, and which role do these molecules play in CeM behavioral circuits? Second, how do CeM inhibitory circuits encode anxiety behaviors, and can this knowledge be used to identify new circuitry treatment targets? The proposed research will provide novel fundamental insights into the mechanisms by which CeM inhibitory synapses control behavior, a critical step in the development of new targeted treatments for amygdala-based psychiatric disorders such as pathological anxiety.

• DFG Programme: Research Grants