Gene expression in the conversion of early-phase to late-phase long-term potentiation

Changes in gene expression associated with different forms of synaptic plasticity in rat hippocampus were investigated. Microarray analysis revealed differential expression of hundreds of genes 30 min after synaptic or antidromic stimulation in different patterns. Results of selected genes were verified by LightCycler RT-PCR. Synaptic activation in a theta burst protocol, which induced long-term potentiation (LTP), increased the mRNA abundance of BDNF-exon 1, but antidromic stimulation in the presence of CNQX, APV, and MCPG (to block glutamatergic synapses) decreased the level of mRNA of this transcript, as did 1 Hz synaptic stimulation. The opposite regulation of this BDNF transcript after firing of the postsynaptic neuron, coincidently or uncorrelated with synaptic firing, is consistent with the effects of BDNF on synaptic transmission, suggesting possible involvement in strengthening and weakening CA1 synapses after correlated versus uncorrelated firing of the postsynaptic neurons with its synaptic inputs. Possible involvement of transcriptional regulation of BDNF in the conversion of early-phase LTP to late-phase LTP are discussed in the context of previous studies by Dudek & Fields (Proc. Natl. Acad. Sci. USA 99: 3962-3967) showing that this conversion can be induced by antidromic stimulation of CA1 neurons in the absence of excitatory synaptic activity.