Consistent with this idea, blocking SK channel activation, and thereby the impact of SK channels on NMDAR function, can promote and enhance long-term potentiation (LTP) evoked by tetanic stimulation in pyramidal neurons from the hippocampus ( Behnisch and Reymann, 1998 Stackman et al., 2002) and amygdala ( Faber et al., 2005). Given the central role of NMDAR activation and calcium in synaptic plasticity ( Bliss and Collingridge, 1993 Yang et al., 1999), the capacity of SK channels to influence NMDAR activation and calcium influx into spines during EPSPs and APs is likely to have consequences on the induction of synaptic plasticity. In addition to their impact on EPSPs, we recently showed in cortical pyramidal neurons that SK channels in spines also act to limit calcium influx into spines and dendrites during backpropagating APs ( Jones and Stuart, 2013). These studies indicate that during EPSPs in pyramidal neurons in the hippocampus and amygdala SK channels in spines form a negative feedback loop controlling EPSP amplitude and calcium influx ( Bloodgood and Sabatini, 2007 Faber et al., 2005 Ngo-Anh et al., 2005). This earlier work has shown that calcium influx into spines during EPSPs leads to SK channel activation, which acts to reduce NMDA receptor (NMDAR) activation presumably by promoting voltage-dependent magnesium block ( Mayer et al., 1984 Nowak et al., 1984). Small conductance calcium-activated potassium channels (SK channels) in spines regulate the amplitude of EPSPs in pyramidal neurons in the hippocampus and amygdala ( Bloodgood and Sabatini, 2007 Faber et al., 2005 Ngo-Anh et al., 2005). These findings indicate that activation of SK channels in spines by backpropagating APs plays a key role in regulating both EPSP amplitude and STDP induction. As a result SK channel activation by backpropagating APs gated STDP induction during low-frequency AP-EPSP pairing, with both LTP and LTD absent under control conditions but present after SK channel block. In cortical pyramidal neurons EPSP suppression by preceding APs depended on their precise timing as well as the distance of activated synapses from the soma, was dendritic in origin, and involved SK-dependent suppression of NMDA receptor activation. Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs).
0 kommentar(er)
