SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala

Abstract

At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is required for long-term potentiation (LTP); this is a proposed cellular mechanism underlying memory and learning. Here we show that in lateral amygdala pyramidal neurons, SK channels are also activated by calcium influx through synaptically activated NMDARs, resulting in depression of the synaptic potential. Thus, blockade of SK channels by apamin potentiates fast glutamatergic synaptic potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2-amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA. Blockade of SK channels greatly enhances LTP of cortical inputs to lateral amygdala pyramidal neurons. These results show that NMDARs and SK channels are colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy.

Organization and Regulation of Small Conductance Ca2+-activated K+Channel Multiprotein Complexes

“…CK2 is enriched in brain, particularly the dendritic arbor (Krek et al, 1992;Moreno et al, 1999). In dendritic spines (Faber et al, 2005;Ngo-Anh et al, 2005) and shafts (Cai et al, 2004), SK2 channels form functional Ca 2ϩ -mediated feedback loops with their Ca 2ϩ sources, NMDA receptors, or voltagedependent Ca 2ϩ channels. The influx of Ca 2ϩ through these Ca 2ϩ sources activates nearby SK2 channels, exerting a repolarizing influence on the membrane potential that ultimately could lead to an attenuation of Ca 2ϩ influx.…”

“…In various neurons, SK channels influence somatic excitability by contributing to afterhyperpolarization (Stocker et al, 1999;Abel et al, 2004), modulate synaptic plasticity by coupling to NMDA receptors (Stackman et al, 2002;Faber et al, 2005;Ngo-Anh et al, 2005), and influence dendritic Ca 2ϩ levels (Cai et al, 2004). By exerting a repolarizing conductance in response to increased intracellular Ca 2ϩ , SK channels effectively form a Ca 2ϩ -mediated feedback loop with their Ca 2ϩ sources.…”

Ionic and neuromodulatory regulation of burst discharge controls frequency tuning

“…SK channels can regulate numerous aspects of neuronal dynamics including: spike frequency adaptation (Pedarzani et al, 2005), dendrosomatic coupling (Cai et al, 2004), as well as synaptic integration and potentiation (Faber et al, 2005;Ngo-Anh et al, 2005). The links between SK channel kinetics and behaviourally relevant neuronal computations have only recently begun to be examined for the SK2 subtype (Ellis et al, 2007b).…”

SK Channels Provide a Novel Mechanism for the Control of Frequency Tuning in Electrosensory Neurons

“…Small conductance calcium-activated potassium (SK) channels (Kohler et al, 1996) open in response to elevations in calcium and produce a medium afterhyperpolarization (mAHP). SK channels can regulate numerous aspects of neuronal dynamics including the following: spike frequency adaptation (Pedarzani et al, 2005), spike patterning (Wolfart et al, 2001;Cloues and Sather, 2003), synaptic excitability (Stackman et al, 2002;Kramar et al, 2004), dendrosomatic coupling (Womack and Khodakhah, 2003), and long-term potentiation (Behnisch and Reymann, 1998;Lancaster et al, 2001;Stackman et al, 2002;Faber et al, 2005;Ngo-Anh et al, 2005). The links between SK channel kinetics and behaviorally relevant neuronal computations have not, however, been rigorously explored.…”