Selective cell adhesion drives synaptic specificity in the hippocampus

Precise neuronal circuit connectivity is critical for normal brain function, yet the mechanisms driving synaptic specificity are poorly understood. Cell adhesion molecules, which can simultaneously mediate axon‐dendrite communication and initiate intracellular signaling processes, are ideally suited to guide specific synapse formation. I will discuss our latest research investigating the role of selective cell adhesion in the development of synaptic specificity in the mouse hippocampus. Currently, we are using 3D serial blockface scanning electron microscopy, proteomics, and crispr/cas gene editing to define precise synaptic defects caused by the loss of specific adhesion molecules. Surprisingly, we find even subtle synaptic changes can significantly impact circuit function. So far, our bottom up approach from cells to circuits has identified adhesion molecules that are repeatedly associated with cognitive and psychiatric disorders. Thus our results have potential to provide critical insights to the specific cellular and circuit changes underlying these complex neurological disorders. Support or Funding Information Our research is funded by grants from the NIMH and Sloan, Mallinckrodt, and Whitehall Foundations.