Role of cadherins in synapse-specific plasticity

Single neurons often receive synapses with distinct properties. However, the molecules regulating these distinct properties remain largely unknown. This dissertation focuses on deciphering such molecules using the mammalian hippocampus as the model system. Hippocampal CA3 neurons form synapses with CA1 neurons at two distinct layers, stratum oriens (SO) and stratum radiatum (SR). SO synapses possess higher levels of long-term potentiation (LTP) and large headed dendritic spines (mushroom spines) compared to SR synapses. Results in Chapter 3 discuss the identification of a synaptic specificity molecule cadherin-9 that is expressed in the CA3 neurons. Genetic deletion of cadherin-9 resulted in reduction of the enhanced levels of LTP and mushroom spines in CA1 SO synapses without affecting the SR synapses. Using in vitro studies cadherins-6 and 10, expressed specifically in the CA1 neurons, were identified to be the postsynaptic binding partners of cadherin-9. Further, deletion of the postsynaptic cadherins resulted in reduced LTP and mushroom spines specifically in the CA1 SO layer similar to the phenotypes observed by deletion of cadherin-9. These results describe a novel functional heterophilic interaction between cadherins-6, 9, and 10 that regulate unique properties specific to one set of synapses without affecting other synapses in the same neuron.