Temporal synaptic tagging by Ih activation and actin:: Involvement in long-term facilitation and cAMP-induced synaptic enhancement

Presynaptic I-h channels become activated during a tetanus through membrane hyperpolarization resulting from Na+ accumulation and electrogenic Na+/K+ exchange. I-h activation is obligatory for inducing long-term facilitation (LTF), a long-lasting synaptic strengthening. cAMP-induced synaptic enhancement also requires I-h activation, and both processes are sensitive to actin depolymerization. Other mechanisms are responsible for expression of the responses. Once initiated, continued response to cAMP is I-h and actin independent. Moreover, LTF-induced activation of I-h renders subsequent cAMP enhancement insensitive to both I-h blockers and actin depolymerization. This actin-stabilized "temporal synaptic tagging" set by I-h activation is prolonged when I-h is activated concurrent with an elevation in presynaptic calcium concentration ([Ca2+](i)), permitting the further strengthening of synapses given appropriate additional stimuli.