POSTSYNAPTIC MODULATION OF SYNAPTIC EFFICACY AT MIXED SYNAPSES ON THEMAUTHNER CELL

Extracellular application of dopamine in the synaptic bed of the later al dendrite of the goldfish Mauthner (M-) cell enhances both the elect rical and chemical components of the mixed excitatory postsynaptic pot ential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda e t. al., 1992). We describe here results of experiments designed to det ermine the locus of action of dopamine and the underlying cellular mec hanisms. This amine acts independently on the two modes of transmissio n, since (1) the percentage increases in the two were not correlated, (2) the time courses of their modifications were independent, and (3) the observed increases in synaptic responses cannot be attributed to a generalized effect on M-cell input conductance, which was increased b y dopamine, a change that would rather be expected to shunt the synapt ic potentials. Also, dopamine does not produce presynaptic spike broad ening and does not modify paired-pulse facilitation, two indications t hat it acts postsynaptically. The alterations in the mixed EPSP are pr esumably due to activation of a postsynaptic cAMP-dependent phosphoryl ation pathway. Specifically, they did not occur if the cAMP-dependent protein kinase inhibitor PKI5-24 was injected intradendritically prior to dopamine application, and they could, on the other hand, be mimick ed by injections of the catalytic subunit of the cAMP-dependent protei n kinase, PKA(CAT). In contrast, neither manipulation altered the M-ce ll input conductance directly or affected the dopamine-induced increas e in conductance, suggesting this effect of dopamine is cAMP independe nt. However, all the dopamine actions were reproduced by intradendriti c injections of GTP-gamma-S, and by dopamine D-1 receptor activation ( Pereda et. al., 1992), indicating a divergence of the intracellular re gulatory pathways, with the possible involvement of multiple G protein s and second messenger systems. These findings provide strong evidence that dopamine modulates the two components of these mixed excitatory synapses by separate postsynaptic mechanisms, probably involving cAMP- dependent phosphorylations of both glutamate receptors and of the M-ce ll side of gap junction channels. Thus, electrotonic synapses may well have distinct pre- and postsynaptic regulatory sites.