TY - JOUR T1 - Role of Hippocampal Ca<sub>v</sub>1.2 Ca<sup>2+</sup> Channels in NMDA Receptor-Independent Synaptic Plasticity and Spatial Memory JF - The Journal of Neuroscience JO - J. Neurosci. SP - 9883 LP - 9892 DO - 10.1523/JNEUROSCI.1531-05.2005 VL - 25 IS - 43 AU - Sven Moosmang AU - Nicole Haider AU - Norbert Klugbauer AU - Helmuth Adelsberger AU - Nicolas Langwieser AU - Jochen Müller AU - Michael Stiess AU - Else Marais AU - Verena Schulla AU - Lubica Lacinova AU - Sandra Goebbels AU - Klaus-Armin Nave AU - Daniel R. Storm AU - Franz Hofmann AU - Thomas Kleppisch Y1 - 2005/10/26 UR - http://www.jneurosci.org/content/25/43/9883.abstract N2 - 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 (Cav1.2HCKO). 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. ER -