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Role of hippocampal Cav1.2 Ca2+ channels in NMDA receptor-independent synaptic plasticity and spatial memory.

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.

Pubmed ID: 16251435

Authors

  • 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
  • Kleppisch T

Journal

The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

October 26, 2005

Associated Grants

None

Mesh Terms

  • 2-Amino-5-phosphonovalerate
  • Animals
  • Anisomycin
  • Behavior, Animal
  • Butadienes
  • Calcium Channels, L-Type
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Radiation
  • Drug Interactions
  • Electric Stimulation
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Fluorescent Antibody Technique
  • Gene Expression Regulation
  • Hippocampus
  • Membrane Potentials
  • Memory
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins
  • Neuronal Plasticity
  • Nitriles
  • Patch-Clamp Techniques
  • Potassium Channel Blockers
  • Protein Synthesis Inhibitors
  • Pyramidal Cells
  • Receptors, N-Methyl-D-Aspartate
  • Spatial Behavior
  • Tetraethylammonium
  • Time Factors