UC Riverside

Across this dissertation we investigate how a synaptic cell adhesion molecule, latrophilin-2 is involved with circuit development in the medial entorhinal cortex, a region implicated in spatial learning. We do a thorough analysis of brain wide protein localization alongside cell-type specific expression analysis to determine which neurons express latrophilin-2 and where that expression is most enriched. We find latrophilin-2 controls spine development for local pyramidal neurons and neurons retrogradely labelled from the ipsilateral pre-subiculum are reduced when latrophilin-2 is deleted, but other inputs remain similar. Following this study, we created a mouse line in which latrophilin-2 expression was removed specifically from the medial entorhinal cortex layer 3 neurons. Using these mice we found distinct differences for localization of input axons, and deficits in acquisition of sequential spatial learning. Together this suggests latrophilin-2 is crucial in assembly of entorhinal circuitry and distinct functions of these cells.