Abstract
Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent changes in excitability are mediated by modulation of intrinsic currents which alters the responsiveness of the cell to synaptic inputs. The afterhyperpolarization (AHP), a major contributor to the regulation of neuronal excitability, is reduced in animals that have acquired several types of hippocampus-dependent memory tasks and also following synaptic potentiation by high frequency stimulation. BK channels underlie the fast AHP and contribute to spike repolarization, and this AHP is reduced in animals that successfully acquired trace-eyeblink conditioning. This suggests that BK channel function is activity-dependent, but the mechanisms are unknown. In this study, we found that blockade of BK channels with paxilline (10 μM) decreased IAHP amplitude and increased spike half-width and instantaneous frequency in response to a +100 pA depolarization. In addition, induction of long term potentiation (LTP) by theta burst stimulation (TBS) in CA1 pyramidal neurons reduced BK channel’s contribution to IAHP, spike repolarization, and instantaneous frequency. This result indicates that BK channel activity is decreased following synaptic potentiation. Interestingly, blockade of mammalian target of rapamycin (MTORC1) with rapamycin (400 nM) following synaptic potentiation restored BK channel function, suggesting a role for protein translation in signaling events which decreased postsynaptic BK channel activity following synaptic potentiation.
Highlights
N-methyl-D-aspartate (NMDA) receptor-dependent long term potentiation (LTP) in area CA1 of the hippocampus has been linked to persistent changes in the intrinsic properties of the postsynaptic neurons and neuronal excitability (Daoudal and Debanne, 2003; Frick et al, 2004; Fan et al, 2005; Xu et al, 2005; Narayanan and Johnston, 2007; Jung et al, 2008)
There was no significant interaction of paxilline and spike number (F(3,107) = 0.18, p = 0.91). This suggests that BK channels play a role in spike repolarization, but they play no role in the spike widening across the train as previously reported in rat CA1 cells (Shao et al, 1999)
Paxilline application caused a significant increase in instantaneous firing frequency of the first five spikes (Figures 2E,F; F(1,18) = 26.04; p < 0.0001), and there was a significant effect of interval number (F(3,54) = 10.80; www.frontiersin.org p < 0.0001), and no significant interaction (F(3,54) = 0.73, p = 0.54, n = 17). These results suggest that currents provided by BK channels contribute to spike repolarization and instantaneous frequency
Summary
N-methyl-D-aspartate (NMDA) receptor-dependent long term potentiation (LTP) in area CA1 of the hippocampus has been linked to persistent changes in the intrinsic properties of the postsynaptic neurons and neuronal excitability (Daoudal and Debanne, 2003; Frick et al, 2004; Fan et al, 2005; Xu et al, 2005; Narayanan and Johnston, 2007; Jung et al, 2008). The BK channels are voltage- and Ca2+-gated K+ channels that contribute to the fast AHP current (IfAHP; Lancaster and Nicoll, 1987; Storm, 1987) as well as action potential repolarization (Faber and Sah, 2003). Another family, the M-channels (Kv7/KCNQ), contributes to the medium AHP (ImAHP; Yue and Yaari, 2004, 2006; Hu et al, 2007), and this family of channels is important for synaptic integration and facilitation of LTP (Shah et al, 2011; Lee and Kwag, 2012; Petrovic et al, 2012)
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