Diverse roles of intracellular cAMP in early synaptic modifications in the rat visual cortex.

1. The effects of increasing intracellular cAMP concentration were studied using photolysis of caged-cAMP in layer II/III neurons recorded intracellularly in visual cortex slices. The recorded neurons exhibited either after-hyperpolarization (AHP) or after-depolarization (ADP) in response to depolarizing current injection. Depending on which afterpotential appeared, the effects of photolysis differed. 2. In ADP-generating neurons, photolysis of caged-cAMP induced long-lasting depression of postsynaptic potentials (PSPs) evoked by grey matter (GM) stimulation, without altering the size of the ADP. In AHP-generating neurons, photolysis induced long-lasting potentiation of GM-evoked PSPs, with the size of the AHP reduced in the same time course. White matter (WM)-evoked PSPs showed no change. 3. Extracellular application of bromo-cAMP depressed both GM- and WM-evoked PSPs in ADP- and AHP-generating neurons. This depression may be due to presynaptic effects of cAMP, since photolysis-evoked postsynaptic increase in cAMP concentration never induced depression of PSPs in AHP-generating neurons. This depression was reversible but continued until bromo-cAMP was washed out, while ADP and AHP in the postsynaptic neurons were depressed only temporarily and returned to the pre-application level even in the continued presence of bromo-cAMP. 4. Bromo-cAMP was applied following photolysis of caged-cAMP. In the neurons in which the photolysis potentiated GM-evoked PSPs this potentiation was cancelled out by bromo-cAMP (depotentiation). In the other neurons, PSPs were depressed only reversibly. 5. Thus, a postsynaptic increase in cAMP concentration exerts more diverse effects on synaptic plasticity than thus far reported, depending on the difference in neuronal intrinsic excitability and probably on how much, or the way in which, cAMP concentration is increased.