NUMEROUS CANDIDATE PLASTICITY-RELATED GENES REVEALED BY DIFFERENTIAL CDNA CLONING

PLASTICITY is a property of the nervous system that allows it to modif y its response to an altered input. This capacity for change suggests that there are molecular mechanisms in neurons that can couple stimuli to long-term alterations in phenotype1-3. Neuronal excitation elicits rapid transcriptional activation of several immediate-early genes4, f or example c-fos, c-jun and zif268. Many immediate-early genes encode transcription factors that control expression of downstream genes whos e products are believed to bring about long-term plastic changes3,4. H ere we use a highly sensitive differential complementary DNA cloning p rocedure to identify genes that may participate in long-term plasticit y. We cloned 52 cDNAs of genes induced by the glutamate analogue kaina te in the hippocampus dentate gyrus. The number of these candidate pla sticity-related genes (CPGs) is estimated to be 500-1,000. One of the cloned CPGs (16C8), encoding a protease inhibitor, is induced by a sti mulus producing long-term potentiation and during dentate gyrus develo pment; a second, cpg1, is dependent on activation of the NMDA (N-methy l-D-aspartate) receptor for induction and encodes a new small, dentate -gyrus-specific protein. Seventeen of the cloned CPGs encode known pro teins, including six suggesting that strong neuronal activation leads to de novo synthesis of vesicular and other synaptic components.