Dendritic small conductance calcium-activated potassium channels activated by action potentials suppress EPSPs and gate spike-timing dependent synaptic plasticity.

Scott L Jones,Minh-Son To,Greg J Stuart

doi:10.7554/elife.30333

Scott L Jones, Minh-Son To + Show 1 more

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https://doi.org/10.7554/elife.30333

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Abstract

Small conductance calcium-activated potassium channels (SK channels) are present in spines and can be activated by backpropagating action potentials (APs). This suggests they may play a critical role in spike-timing dependent synaptic plasticity (STDP). Consistent with this idea, EPSPs in both cortical and hippocampal pyramidal neurons were suppressed by preceding APs in an SK-dependent manner. 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. 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. 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.

Highlights

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)
The magnitude of SK-dependent EPSP suppression was dependent on the precise timing of EPSPs and postsynaptic action potentials (APs), with EPSP suppression only observed when postsynaptic APs were evoked within a brief time window before EPSP onset (Figure 1d,e; n = 6)
We show that backpropagating APs suppress EPSPs in both cortical and hippocampal pyramidal neurons if generated within a brief time window before EPSP onset

Summary

Introduction

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). 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) 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). 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

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