A novel murine cDNA which encodes a protein designated neuropsin was cloned. Northern and in situ hybridization analyses demonstrated that neuropsin mRNA is expressed specifically in the limbic system of mouse brain and is localized at highest concentration in pyramidal neurons of the hippocampal CA1-3 subfields. Direct hippocampal stimulation and kindling induced by amygdaloid stimulation caused a significant bilateral change in neuropsin mRNA level in the hippocampal pyramidal neurons. The activity-dependent changes and the specific localization indicate that neuropsin is involved in hippocampal plasticity.