Antibodies to postsynaptic PKC substrate neurogranin prevent long-term potentiation in hippocampal CA1 neurons.

Both pre- and postsynaptic protein kinase C have been implicated in long-term potentiation. Neurogranin (also known as BICKs and RC3) is a neuronal postsynaptic protein kinase C substrate. In the present study we injected monoclonal IgGs that recognize the protein kinase C phosphorylation site in neurogranin and B-50 (GAP-43), and that have been shown to inhibit protein kinase C-mediated B-50 phosphorylation, through a whole-cell clamp pipette into CA1 pyramidal neurons in rat hippocampal slices. Injection of neurogranin IgGs, but not of control IgGs, prevented the induction of tetanus-induced long-term potentiation without affecting post-tetanic potentiation. Our results suggest that neurogranin is involved in mechanisms of activity-dependent synaptic plasticity.