Dendritic mechanisms controlling the threshold and timing requirement of synaptic plasticity

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(+) channels and Ca(2+) -activated K(+) channels are involved in the induction process of Hebbian-type 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(+) currents in Kv4.2(-/-) 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(-/-) 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(2+) -activated K(+) channels also exerted a sliding effect on synaptic plasticity. Blocking these channels in Kv4.2(-/-) mice resulted in an even larger potentiation while by contrast, the depression threshold was shifted further. In conclusion, dendritic A-type and Ca(2+) -activated K(+) channels dually regulate the timing-dependence and thresholds of synaptic plasticity in an additive way.