Cyclic GMP-dependent feedback inhibition of AMPA receptors is independent of PKG

In central neurons, the second messenger cGMP is believed to induce long-te rm changes in efficacy at glutamatergic synapses through activation of prot ein kinase C (PKC). Stimulating nitric oxide synthase, activating soluble g uanylyl cyclase or elevating concentrations of intracellular cGMP depressed excitatory synaptic transmission in CA1 hippocampal neurons. Unexpectedly, intracellular cGMP depressed responses of AMPA receptors and inhibited exc itatory postsynaptic currents in hippocampal neurons independently of phosp horylation. Our findings demonstrate that cGMP's modulation of excitatory t ransmission may involve a coupling of AMPA channel activity to levels of cG MP.