Induction of long-term potentiation (LTP) in the dentate gyrus of awake rats triggered a rapid (2 hour) elevation in tyrosine kinase receptor (trkB and trkC) gene expression and a delayed (6-24 hour) increase in brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) gene expression. Depending on the mRNA species, LTP induction led to highly selective unilateral or bilateral increases in gene expression. Specifically, trkB and NT-3 mRNA elevations were restricted to granule cells in the ipsilateral dentate gyrus, whereas bilateral increases in trkC, BDNF, and nerve growth factor (NGF) mRNA levels occurred in granule cells and hippocampal pyramidal cells. Both unilateral and bilateral changes in gene expression were N-methyl-D-aspartate (NMDA) receptor-dependent and LTP-specific. Bilateral electrophysiological recordings demonstrated that LTP was unilaterally induced; this was corroborated by a dramatic unilateral increase in the expression of the immediate early gene zif/268, a marker for LTP, restricted to the ipsilateral granule cells. The results indicate that LTP triggers an interhemispheric communication manifested as selective, bilateral increases in gene expression at multiple sites in the hippocampal network. Furthermore, our findings suggest that physiological plastic changes in the adult brain may involve coordinated, time-dependent regulation of multiple neurotrophin and trk receptor genes.