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To evaluate the contributions of the pre- versus postsynaptic expression of NCAM in regulation of synaptic efficacy, we cultured dissociated hippocampal cells from NCAM-deficient and wild-type mice in homo- and heterogenotypic combinations. Double recordings from synaptically coupled neurons maintained in heterogenotypic cocultures showed that synaptic strength of excitatory but not inhibitory synapses depended on expression of NCAM post- but not presynaptically. This correlated with higher levels of potentiation and synaptic coverage of NCAM-expressing neurons compared to NCAM-deficient neurons in heterogenotypic cocultures. Synaptic density was the same in homogenotypic cultures of NCAM-deficient and wild-type neurons as well as in heterogenotypic cocultures in which glutamate receptors were blocked. These observations indicate that the relative levels of postsynaptic NCAM expression …