Dendritic mechanisms controlling the threshold and timing requirement of synaptic plasticity

Abstract

ABSTRACT:Active conductances located and operating on neuronal dendrites are expected to regulate synaptic integration and plasticity. We investigate how Kv4.2-mediated A-type K 1 channels and Ca 21 -activated K 1 channels are involved in the induction process of Hebbiantype plasticity that requires correlated pre-and postsynaptic activities. In CA1 pyramidal neurons, robust long-term potentiation (LTP) induced by a theta burst pairing protocol usually occurred within a narrow window during which incoming synaptic potentials coincided with postsynaptic depolarization. Elimination of dendritic A-type K 1 currents in Kv4.2 2/2 mice, however, resulted in an expanded time window, making the induction of synaptic potentiation less dependent on the temporal relation of pre-and postsynaptic activity. For the other type of synaptic plasticity, long-term depression, the threshold was significantly increased in Kv4.2 2/2 mice. This shift in depression threshold was restored to normal when the appropriate amount of internal free calcium was chelated during induction. In concert with A-type channels, Ca 21 -activated K 1 channels also exerted a sliding effect on synaptic plasticity. Blocking these channels in Kv4.2 2/2 mice resulted in an even larger potentiation while by contrast, the depression threshold was shifted further. In conclusion, dendritic A-type and Ca 21 -activated K 1 channels dually regulate the timing-dependence and thresholds of synaptic plasticity in an additive way. V V C 2010 Wiley-Liss, Inc.

Kv4 potassium channels modulate hippocampal EPSP-spike potentiation and spatial memory in rats

“…Conversely, when the expression of a Kv4.2 subunit is decreased in a dominant-negative model, the opposite effects are observed ( Jung et al 2008). Furthermore, the elimination of dendritic A-type K + currents in Kv4.2 knockdown mice enhances b-AP amplitude, increases neuronal excitability, and facilitates LTP induction in hippocampal neurons (Kim et al 2005(Kim et al , 2007Chen et al 2006;Andrásfalvy et al 2008;Zhao et al 2011). Shen et al (2008) have shown that enhancing excitatory input by glutamate in cortical neurons increases Kv4-channel-mediated K + current and, as a consequence, negatively regulated neuronal excitability.…”

“…Among the A-type potassium channels, the Kv4 channels adjust dendritic function by limiting spike-timing-dependent plasticity. This mode of action requires the co-occurrence of an EPSP and a b-AP Johnston 1997, 2005;Birnbaum et al 2004;Zhao et al 2011).…”

Spatial learning deficits in mice lacking A‐type K+ channel subunits

“…b-APs serve as a physiological form of membrane depolarization that controls NMDA receptor activity, thus they participate in NMDA receptor-dependent synaptic plasticity. As a result of I A elimination in Kv4.2 knockout (KO) mice, CA1 neurons exhibit an expanded time window for signal integration at synapses located in distal dendrites, making the induction of synaptic potentiation less dependent on the temporal relation between pre-and postsynaptic activity (Zhao et al, 2010). Furthermore, the plasticity threshold in CA1 neurons of Kv4.2 KO is shifted in a direction that favors synaptic potentiation (long-term potentiation (LTP)) and disfavors synaptic depression (Chen et al, 2006;Zhao et al, 2010).…”

“…As a result of I A elimination in Kv4.2 knockout (KO) mice, CA1 neurons exhibit an expanded time window for signal integration at synapses located in distal dendrites, making the induction of synaptic potentiation less dependent on the temporal relation between pre-and postsynaptic activity (Zhao et al, 2010). Furthermore, the plasticity threshold in CA1 neurons of Kv4.2 KO is shifted in a direction that favors synaptic potentiation (long-term potentiation (LTP)) and disfavors synaptic depression (Chen et al, 2006;Zhao et al, 2010). Given the high expression level of Kv4.2 in the hippocampus (Serodio and Rudy, 1988), and the well-established role of synaptic plasticity in learning and memory, we suspected that KO mice might show behavioral changes in hippocampal-dependent task acquisition and retention.…”

Deletion of novel protein TMEM35 alters stress-related functions and impairs long-term memory in mice

“…Hippocampal slices were prepared following previously described protocols (78). P65 mice were deeply anesthetized with an overdose of ketamine/xylazine and perfused with icecold buffer, consisting of (in mM): 119 NaCl, 2.5 KCl, 1.3 MgSO4, 1.0 NaH2PO4, 26.2 NaHCO3, 2.5 CaCl2, and 10.0 dextrose.…”