A dopamine- and protein kinase A-dependent mechanism for network adaptation in retinal ganglion cells

Vertebrates can detect light intensity changes in vastly different photic e nvironments, in part, because postreceptoral neurons undergo "network adapt ation." Previous data implicated dopaminergic, cAMP-dependent inhibition of retinal ganglion cells in this process yet left unclear how this occurs an d whether this occurs in darkness versus light. To test for light- and dopa mine-dependent changes in ganglion cell cAMP levels in situ, we immunostain ed dark- and light-adapted retinas with anti-cAMP antisera in the presence and absence of various dopamine receptor ligands. To test for direct effect s of dopamine receptor ligands and membrane-permeable protein kinase ligand s on ganglion cell excitability, we recorded spikes from isolated ganglion cells in perforated-patch whole-cell mode before and during application of these agents by microperfusion. Our immunostainings show that light, endoge nous dopamine, and exogenous dopamine elevate ganglion cell cAMP levels in situ by activating D1-type dopamine receptors. Our spike recordings show th at D1-type agonists and 8-bromo cAMP reduce spike frequency and curtail sus tained spike firing and that these effects entail protein kinase A activati on. These effects resemble those of background light on ganglion cell respo nses to light flashes. Network adaptation could thus be produced, to some e xtent, by dopaminergic modulation of ganglion cell spike generation, a mech anism distinct from modulation of transmitter release onto ganglion cells o r of transmitter-gated currents in ganglion cells. Combining these observat ions with results obtained in studies of photoreceptor, bipolar, and horizo ntal cells indicates that all three layers of neurons in the retina are equ ipped with mechanisms for adaptation to ambient light intensity.