0. Difference was considered significant at p value < 0.05. We are grateful to Dr. J. Melki, Dr. S. Arber, and Dr. L.A. Niswander for valuable mouse lines; Dr. S. Pfaff, Dr. R. Rotundo, Dr. Z. Hall, and Dr. T. Suzuki for valuable reagents; and Dr. Chien-Ping Ko for advice on EM analysis. We thank members of the Mei and Xiong laboratories for discussion. This work was supported in part by grants from National Institutes of Health (NS040480 and NS056415, L.M. and W.C.X.) and Muscular Dystrophy Association (L.M.). "
“Dendritic excitability is determined by the activity of voltage- and calcium-dependent ion channels that contribute to the input-output function Baf-A1 of neurons (Häusser

et al., 2000). Alterations in these active properties adjust dendritic integration and complement forms of synaptic plasticity, such as long-term potentiation (LTP) and long-term depression (LTD), in information storage (Daoudal and Small molecule library Debanne, 2003, Magee and Johnston, 2005 and Zhang and Linden, 2003). For example, dendritic processing of intrinsic and synaptic signals is influenced by different calcium-activated K conductances (KCa) that

may contribute to the afterhyperpolarization (AHP) following spike activity (Sah, 1996 and Stocker et al., 1999) or accelerate the repolarization of excitatory postsynaptic potentials (EPSPs) (Lancaster et al., 2001). One class of (KCa), small conductance calcium-activated SK-type K channels act as a brake on dendritic responsiveness and calcium signaling. In hippocampus, blocking SK channels with apamin prolongs dendritic responses (Cai et al., 2004) and potentiates EPSP-spike coupling (Sourdet et al., 2003). In the amygdala and hippocampus, blocking synaptic SK channels enhances spine calcium transients leading to an increased probability for the induction of LTP (Faber et al., 2005, Lin et al., 2008 and Ngo-Anh et al., 2005). In line with

these observations, modulating SK channel activity influences hippocampus-dependent memory encoding (Hammond et al., 2006 and Stackman et al., 2002). In cerebellar Purkinje cells, a form of 17-DMAG (Alvespimycin) HCl intrinsic plasticity that is mediated by SK channel downregulation is associated with enhanced spine calcium transients, but in contrast to the hippocampus, this increased calcium signaling results in a lower probability for LTP induction (Belmeguenai et al., 2010 and Hosy et al., 2011), possibly reflecting different calcium signaling requirements for hippocampal and cerebellar LTP (Coesmans et al., 2004). We used dendritic patch-clamp recordings from rat Purkinje cells in freshly prepared brain slices and found that SK channel downregulation affects the processing of activity patterns in Purkinje cell dendrites, enhancing their intrinsic excitability (IE). The excitability of Purkinje cell dendrites can be altered in response to either synaptic or nonsynaptic tetanization patterns.