title: Critical involvement of postsynaptic protein kinase activation in long-term potentiation at hippocampal mossy fiber synapses on CA3 interneurons.
abstract: 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 PKI(6-22) failed to be maintained. Consistent with these data, delivery of HFS to MFs synapsing onto L-M interneurons loaded with PKI(6-22) 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.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
authors.forename: Emilio J
authors.initials: EJ
authors.lastname: Galván
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Cosgrove
authors.forename: Jocelyn C
authors.initials: JC
authors.lastname: Mauna
authors.forename: J Patrick
authors.initials: JP
authors.lastname: Card
authors.forename: Edda
authors.initials: E
authors.lastname: Thiels
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Meriney
authors.forename: Germán
authors.initials: G
authors.lastname: Barrionuevo
mesh_terms: D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D020134:Catalytic Domain / Q000187:drug effects / Q000502:physiology; D005576:Colforsin / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000201:enzymology* / Q000648:ultrastructure; D009924:Organ Culture Techniques; D010446:Peptide Fragments / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000201:enzymology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D047908:Intracellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D010703:Phorbol Esters; D010726:Phosphodiesterase Inhibitors; D018091:Receptors, AMPA; C094636:protein kinase inhibitor (6-22); D005576:Colforsin; C008874:phorbol-12,13-diacetate; D018698:Glutamic Acid; C016299:chelerythrine; D011494:Protein Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D015056:1-Methyl-3-isobutylxanthine