Small Conductance Ca²⁺-Activated K⁺Channels Modulate Synaptic Plasticity and Memory Encoding

Abstract

Activity-dependent changes in neuronal excitability and synaptic strength are thought to underlie memory encoding. In hippocampal CA1 neurons, small conductance Ca 2ϩ -activated K ϩ (SK) channels contribute to the afterhyperpolarization, affecting neuronal excitability. In the present study, we examined the effect of apamin-sensitive SK channels on the induction of hippocampal synaptic plasticity in response to a range of stimulation frequencies. In addition, the role of apamin-sensitive SK channels on hippocampal-dependent memory encoding and retention was also tested. The results show that blocking SK channels with apamin increased the excitability of hippocampal neurons and facilitated the induction of synaptic plasticity by shifting the modification threshold to lower frequencies. This facilitation was NMDA receptor (NMDAR) dependent and appeared to be postsynaptic. Mice treated with apamin demonstrated accelerated hippocampal-dependent spatial and nonspatial memory encoding. They required fewer trials to learn the location of a hidden platform in the Morris water maze and less time to encode object memory in an object-recognition task compared with saline-treated mice. Apamin did not influence long-term retention of spatial or nonspatial memory. These data support a role for SK channels in the modulation of hippocampal synaptic plasticity and hippocampal-dependent memory encoding.

Chronic Intermittent Ethanol Exposure Enhances the Excitability and Synaptic Plasticity of Lateral Orbitofrontal Cortex Neurons and Induces a Tolerance to the Acute Inhibitory Actions of Ethanol

“…For example, the decrease in SK channel function following CIE treatment observed in many regions including the OFC would be expected to enhance synaptic efficacy and plasticity. In support of this, results from previous studies show that blocking these channels facilitates LTP and enhances learning and memory (Blank et al, 2003;Brennan et al, 2008;Hammond et al, 2006;Stackman et al, 2002), whereas overexpression of SK channels reduces LTP and impairs hippocampus-, amygdala-, and mPFC-dependent learning tasks. In addition to changes in glutamate receptor expression and function described above, alterations in dendritic Figure 8 Chronic intermittent ethanol (CIE) exposure suppresses the ability of the GlyT1 transport inhibitor sarcosine to reduce spiking in lateral orbitofrontal cortex (lOFC) neurons.…”

Synaptic plasticity in early aging

“…The results also reinforce a previous conclusion that plasticity of the basal dendritic synapses is significantly different than that in their apical counterparts. Earlier studies had shown that LTP has a lower threshold (requires fewer theta bursts) and is greater in magnitude in the basal than in the apical dendrites in field CA1 (Arai et al, 1994;Roth and Leung, 1995;Leung and Shen, 1999), an effect that can probably be attributed to regional differences in the incidence of potassium channels that mediate the after-hyperpolarizing potentials (AHPs) initiated by individual theta bursts (Arai and Lynch, 1992;Arai et al, 1994;Sah and Bekkers, 1996;Stackman et al, 2002). LTP also differs between the two dendritic domains with regard to the degree to which it stabilizes.…”

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

“…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.…”