Enhancement of synaptic transmission by cyclic AMP modulation of presynaptic I-h channels

Presynaptic activation of adenylyl cyclase and subsequent generation of cAM P represent an important mechanism in the modulation of synaptic transmissi on. In many cases, short- to medium-term modulation of synaptic strength by cAMP is due to activation of protein kinase A and subsequent covalent modi fication of presynaptic ion channels or synaptic proteins. Here we show tha t presynaptic cAMP generation via serotonin receptor activation directly mo dulated hyperpolarization-activated cation channels (I-h channels) in axons . This modulation of I-h produced an increase in synaptic strength that cou ld not be explained solely by depolarization of the presynaptic membrane. T hese studies identify a mechanism by which cAMP and I-h regulate synaptic p lasticity.