xpression and IA activity when compared to wt mice. These results are in agreement with those obtained with similar dream2/2 mice. Moreover, kv4.2 deletion in mice alters the expression of both DREAM and KChIPs, suggesting that the expression of Kv4.2 and DREAM is tightly coupled. It also suggests the existence of a feedback mechanism to prevent the accumulation of free KChIPs or Kv4.2. This could be achieved by coupling KChIP and Kv4.2 gene expression and/or through post-transcriptional/post-translational mechanisms. Importantly, the marked reductions in the expression of KChIP proteins in kv 
4.2 2/2 mice are not evident at the transcriptional level, suggesting that post-translational mechanisms are responsible for the loss of KChIP proteins. In fact, the coexpression of KChIPs and Kv4.2 leads to increased protein stability. Together these findings suggest that the binding of KChIP and Kv4 proteins leads to mutual stabilization, increasing the levels of both the Kv4 subunit and accessory KChIP proteins. The reduction or inhibition of IA expression in vivo results in a decrease in the stimulus threshold required to induce lasting earlyLTP with a single HFS, and a change in the basal electrical oscillatory pattern of the hippocampus. At the cellular level, these alterations may be the consequence of increases in neuronal excitability, and in the dendritic back-propagation of action potential that occurs in the hippocampus in the absence of the IA current. It is important to note that all these hippocampal events have previously been linked to the facilitation of learning and memory. In fact, our results show that decreased IA activity facilitates learning, in contrast to situations in which these events Y27632 dihydrochloride site facilitated both learning and memory. These findings 17449326” suggest that decreased IA is not sufficient to provoke the learning-induced changes in gene expression required for memory consolidation. Hippocampal dendritic Kv4.2 channel surface expression is regulated by synaptic activity and it decreases significantly during synaptic plasticity processes. This suggests a mechanism must exist to control synaptic integration through the regulation of the surface expression of the channels responsible for the IA. Synaptic plasticity processes are also influenced by the NR2 subunit type in NMDA receptors. In young rats LTP induces an immediate change in the NR2 subunit composition of synaptic NMDARs, favoring NR2A over NR2B. However, synaptic NR2B-containing receptors are still present in adult hippocampal synapses, ” suggesting that NR2B subunits are trafficked into the synapse. A relationship between functional IA and the rapid and bidirectional remodeling of synaptic NMDAR subunit composition has been described. Increased IA induces a decrease in the contribution of the NR2B subunit to the total synaptic NMDAR current, while IA knockdown increases the relative NR2B fraction. Thus, IA-dependent remodeling of synaptic NMDAR composition appears to be accompanied by changes in the ability to induce LTP. Here, we report that in vivo reduction of IA facilitated the induction of early-LTP, similar to that produced by overexpression of a mutant Kv4.2 channel in vitro. Whether this effect is due to increased activity of the NR2Bcontaining NMDARs is unknown, and will require further investigation. Nevertheless, the facilitated learning observed in mice following IA reduction was blocked by inhibition of NR2Bcontaining NMDARs, suggesting that both learning and