Postsynaptic modulation of synaptic efficacy at mixed synapses on the Mauthner cell

Extracellular application of dopamine in the synaptic bed of the lateral dendrite of the goldfish Mauthner (M-) cell enhances both the electrical and chemical components of the mixed excitatory postsynaptic potential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda et. al., 1992). We describe here results of experiments designed to determine the locus of action of dopamine and the underlying cellular mechanisms. This amine acts independently on the two modes of transmission, 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 by dopamine, a change that would rather be expected to shunt the synaptic potentials. Also, dopamine does not produce presynaptic spike broadening and does not modify paired-pulse facilitation, two indications that it acts postsynaptically. The alterations in the mixed EPSP are presumably due to activation of a postsynaptic cAMP-dependent phosphorylation pathway. Specifically, they did not occur if the cAMP- dependent protein kinase inhibitor PKI_5-24 was injected intradendritically prior to dopamine application, and they could, on the other hand, be mimicked by injections of the catalytic subunit of the cAMP- dependent protein kinase, PKA(CAT). In contrast, neither manipulation altered the M-cell input conductance directly or affected the dopamine-induced increase in conductance, suggesting this effect of dopamine is cAMP independent. However, all the dopamine actions were reproduced by intradendritic injections of GTP-γ-S, and by dopamine D, receptor activation (Pereda et. al., 1992), indicating a divergence of the intracellular regulatory pathways, with the possible involvement of multiple G proteins 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-cell side of gap junction channels. Thus, electrotonic synapses may well have distinct pre- and postsynaptic regulatory sites.