RT Journal Article SR Electronic T1 Presynaptic Role of cGMP-Dependent Protein Kinase during Long-Lasting Potentiation JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 143 OP 149 DO 10.1523/JNEUROSCI.21-01-00143.2001 VO 21 IS 1 A1 Arancio, Ottavio A1 Antonova, Irina A1 Gambaryan, Stepan A1 Lohmann, Suzanne M. A1 Wood, Jason S. A1 Lawrence, David S. A1 Hawkins, Robert D. YR 2001 UL http://www.jneurosci.org/content/21/1/143.abstract AB Previous research has suggested that cGMP-dependent protein kinases (cGKs) may play a role in long-term potentiation in hippocampus, but their site of action has been unknown. We examined this question at synapses between pairs of hippocampal neurons in dissociated cell culture. Injection of a specific peptide inhibitor of cGK into the presynaptic but not the postsynaptic neuron blocked long-lasting potentiation induced by tetanic stimulation of the presynaptic neuron. As controls, injection of a scrambled peptide or a peptide inhibitor of cAMP-dependent protein kinase into either neuron did not block potentiation. Conversely, injection of the α isozyme of cGK type I into the presynaptic but not the postsynaptic neuron produced activity-dependent potentiation that did not require NMDA receptor activation. Evidence from Western blots, reverse transcription-PCR, activity assays, and immunocytochemistry indicates that endogenous cGK type I is present in the neurons, including presynaptic terminals. These results support the idea that cGK plays an important presynaptic role during the induction of long-lasting potentiation in hippocampal neurons.