PMID:16251435

Citation	Moosmang, S, Haider, N, Klugbauer, N, Adelsberger, H, Langwieser, N, Müller, J, Stiess, M, Marais, E, Schulla, V, Lacinova, L, Goebbels, S, Nave, KA, Storm, DR, Hofmann, F and Kleppisch, T (2005) Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory. J. Neurosci. 25:9883-92
Abstract	Current knowledge about the molecular mechanisms of NMDA receptor (NMDAR)-independent long-term potentiation (LTP) in the hippocampus and its function for memory formation in the behaving animal is limited. NMDAR-independent LTP in the CA1 region is thought to require activity of postsynaptic L-type voltage-dependent Ca2+ channels (Cav1.x), but the underlying channel isoform remains unknown. We evaluated the function of the Cav1.2 L-type Ca2+ channel for spatial learning, synaptic plasticity, and triggering of learning-associated biochemical processes using a mouse line with an inactivation of the CACNA1C (Cav1.2) gene in the hippocampus and neocortex (Cav1.2(HCKO)). This model shows (1) a selective loss of protein synthesis-dependent NMDAR-independent Schaffer collateral/CA1 late-phase LTP (L-LTP), (2) a severe impairment of hippocampus-dependent spatial memory, and (3) decreased activation of the mitogen-activated protein kinase (MAPK) pathway and reduced cAMP response element (CRE)-dependent transcription in CA1 pyramidal neurons. Our results provide strong evidence for a role of L-type Ca2+ channel-dependent, NMDAR-independent hippocampal L-LTP in the formation of spatial memory in the behaving animal and for a function of the MAPK/CREB (CRE-binding protein) signaling cascade in linking Cav1.2 channel-mediated Ca2+ influx to either process.
Links	PubMed Online version:10.1523/JNEUROSCI.1531-05.2005
Keywords	2-Amino-5-phosphonovalerate/pharmacology; Animals; Anisomycin/pharmacology; Behavior, Animal; Butadienes/pharmacology; Calcium Channels, L-Type/deficiency; Calcium Channels, L-Type/physiology; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Drug Interactions; Electric Stimulation/methods; Enzyme Inhibitors/pharmacology; Excitatory Amino Acid Antagonists/pharmacology; Fluorescent Antibody Technique/methods; Gene Expression Regulation/drug effects; Hippocampus/cytology; Hippocampus/physiology; Membrane Potentials/drug effects; Membrane Potentials/physiology; Membrane Potentials/radiation effects; Memory/physiology; Mice; Mice, Knockout; Nerve Tissue Proteins/drug effects; Nerve Tissue Proteins/physiology; Neuronal Plasticity/drug effects; Neuronal Plasticity/physiology; Neuronal Plasticity/radiation effects; Nitriles/pharmacology; Patch-Clamp Techniques/methods; Potassium Channel Blockers/pharmacology; Protein Synthesis Inhibitors/pharmacology; Pyramidal Cells/drug effects; Pyramidal Cells/physiology; Pyramidal Cells/radiation effects; Receptors, N-Methyl-D-Aspartate/physiology; Spatial Behavior/physiology; Tetraethylammonium/pharmacology; Time Factors
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