title: Synapse-specific compartmentalization of signaling cascades for LTP induction in CA3 interneurons.
abstract: Inhibitory interneurons with somata in strata radiatum and lacunosum-molecular (SR/L-M) of hippocampal area CA3 receive excitatory input from pyramidal cells via the recurrent collaterals (RCs), and the dentate gyrus granule cells via the mossy fibers (MFs). Here we demonstrate that Hebbian long-term potentiation (LTP) at RC synapses on SR/L-M interneurons requires the concomitant activation of calcium-impermeable AMPARs (CI-AMPARs) and N-methyl-d-aspartate receptors (NMDARs). RC LTP was prevented by voltage clamping the postsynaptic cell during high-frequency stimulation (HFS; 3 trains of 100 pulses delivered at 100 Hz every 10s), with intracellular injections of the Ca(2+) chelator BAPTA (20mM), and with the NMDAR antagonist D-AP5. In separate experiments, RC and MF inputs converging onto the same interneuron were sequentially activated. We found that RC LTP induction was blocked by inhibitors of the calcium/calmodulin-dependent protein kinase II (CaMKII; KN-62, 10 μM or KN-93, 10 μM) but MF LTP was CaMKII independent. Conversely, the application of the protein kinase A (PKA) activators forskolin/IBMX (50 μM/25 μM) potentiated MF EPSPs but not RC EPSPs. Together these data indicate that the aspiny dendrites of SR/L-M interneurons compartmentalize synapse-specific Ca(2+) signaling required for LTP induction at RC and MF synapses. We also show that the two signal transduction cascades converge to activate a common effector, protein kinase C (PKC). Specifically, LTP at RC and MF synapses on the same SR/LM interneuron was blocked by postsynaptic injections of chelerythrine (10 μM). These data indicate that both forms of LTP share a common mechanism involving PKC-dependent signaling modulation.
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico. Electronic address: ejgalvan@cinvestav.mx.
authors: E J
authors: EJ
authors: Galván
authors: Department of Physiology, Northwestern University, Chicago, IL, USA.
authors: T
authors: T
authors: Pérez-Rosello
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico.
authors: G
authors: G
authors: Gómez-Lira
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico.
authors: E
authors: E
authors: Lara
authors: Departamento de Farmacobiología, Cinvestav Sede Sur, México City, Mexico.
authors: R
authors: R
authors: Gutiérrez
authors: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors: G
authors: G
authors: Barrionuevo
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D007395:Interneurons / Q000187:drug effects / Q000502:physiology*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
keywords: CA3 interneurons; CaMKII; PKA; PKC; calcium impermeable AMPARs; feed-forward inhibition; recurrent commissural LTP and LTD
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