PT - JOURNAL ARTICLE AU - Emilio J. Galván AU - Kathleen E. Cosgrove AU - Jocelyn C. Mauna AU - J. Patrick Card AU - Edda Thiels AU - Stephen D. Meriney AU - Germán Barrionuevo TI - Critical Involvement of Postsynaptic Protein Kinase Activation in Long-Term Potentiation at Hippocampal Mossy Fiber Synapses on CA3 Interneurons AID - 10.1523/JNEUROSCI.5269-09.2010 DP - 2010 Feb 24 TA - The Journal of Neuroscience PG - 2844--2855 VI - 30 IP - 8 4099 - http://www.jneurosci.org/content/30/8/2844.short 4100 - http://www.jneurosci.org/content/30/8/2844.full SO - J. Neurosci.2010 Feb 24; 30 AB - Hippocampal mossy fiber (MF) synapses on area CA3 lacunosum-moleculare (L-M) interneurons are capable of undergoing a Hebbian form of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) induced by the same type of high-frequency stimulation (HFS) that induces LTP at MF synapses on pyramidal cells. LTP of MF input to L-M interneurons occurs only at synapses containing mostly calcium-impermeable (CI)-AMPA receptors (AMPARs). Here, we demonstrate that HFS-induced LTP at these MF-interneuron synapses requires postsynaptic activation of protein kinase A (PKA) and protein kinase C (PKC). Brief extracellular stimulation of PKA with forskolin (FSK) alone or in combination with 1-Methyl-3-isobutylxanthine (IBMX) induced a long-lasting synaptic enhancement at MF synapses predominantly containing CI-AMPARs. However, the FSK/IBMX-induced potentiation in cells loaded with the specific PKA inhibitor peptide PKI6-22 failed to be maintained. Consistent with these data, delivery of HFS to MFs synapsing onto L-M interneurons loaded with PKI6-22 induced posttetanic potentiation (PTP) but not LTP. Hippocampal sections stained for the catalytic subunit of PKA revealed abundant immunoreactivity in interneurons located in strata radiatum and L-M of area CA3. We also found that extracellular activation of PKC with phorbol 12,13-diacetate induced a pharmacological potentiation of the isolated CI-AMPAR component of the MF EPSP. However, HFS delivered to MF synapses on cells loaded with the PKC inhibitor chelerythrine exhibited PTP followed by a significant depression. Together, our data indicate that MF LTP in L-M interneurons at synapses containing primarily CI-AMPARs requires some of the same signaling cascades as does LTP of glutamatergic input to CA3 or CA1 pyramidal cells.