Abstract
Synaptic plasticity involves short- and long-term events, although the molecular mechanisms that underlie these processes are not fully understood. The transient A-type K+ current (IA) controls the excitability of the dendrites from CA1 pyramidal neurons by regulating the back-propagation of action potentials and shaping synaptic input. Here, we have studied how decreases in IA affect cognitive processes and synaptic plasticity. Using wild-type mice treated with 4-AP, an IA inhibitor, and mice lacking the DREAM protein, a transcriptional repressor and modulator of the IA, we demonstrate that impairment of IA decreases the stimulation threshold for learning and the induction of early-LTP. Hippocampal electrical recordings in both models revealed alterations in basal electrical oscillatory properties toward low-theta frequencies. In addition, we demonstrated that the facilitated learning induced by decreased IA requires the activation of NMDA receptors containing the NR2B subunit. Together, these findings point to a balance between the IA and the activity of NR2B-containing NMDA receptors in the regulation of learning.
Highlights
Memory and synaptic plasticity are mediated by two distinct components
We demonstrate that the facilitation of learning induced by IA inhibition is mediated by NMDA receptors (NMDARs) containing the NR2B subunit
We recently reported that dream2/2 mice exhibit long-lasting LTP after a high frequency stimulation (HFS) protocol [30]
Summary
Memory and synaptic plasticity are mediated by two distinct components. The first yields only transient phenomena, short-term memory (STM, lasting minutes to hours) and the early phase of LTP (E-LTP, lasting 0.5–1 hr), while the second involves synaptic changes and the activation of mechanisms that stabilize the memory, resulting in long-term memory (LTM, lasting days, weeks or years), and the late phase of LTP (L-LTP, lasting many hours). Distinct molecular mechanisms are thought to underlie each component [1] since modifications of pre-existing proteins are sufficient for the transient changes, while new gene expression (transcription and translation) is required for sustained changes [1,2,3,4,5,6,7]. Kv4 channels are the main contributors to the potassium Acurrent (IA) [8] These channels are concentrated somatodendritically, where they act as crucial regulators of postsynaptic excitability [9,10,11] and modulators of synaptic plasticity [12,13,14,15,16,17]. NMDAR, especially the NR2B subunit, and Kv4.2 channels activity are mutually regulated to modulate synaptic plasticity [27,28,29]
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