DYE-COUPLING BETWEEN PYRAMIDAL NEURONS IN DEVELOPING RAT PREFRONTAL AND FRONTAL-CORTEX IS REDUCED BY PROTEIN-KINASE-A ACTIVATION AND DOPAMINE

During early postnatal development, lamina II/III pyramidal cells in r at neocortex are extensively coupled via gap junctions. The factors re gulating gap junction permeability, as well as the mechanisms underlyi ng the developmental uncoupling process are not understood. To investi gate the influence of protein kinase A-mediated phosphorylation on dye coupling in the developing neocortex, pyramidal cells in slices of ra t frontal and prefrontal cortex were injected intracellularly with the tracer neurobiotin. Control injections revealed clusters of about 30 dye-coupled neurons, Preincubation with forskolin or direct activation of protein kinase A with Sp-cAMPS reduced the number of coupled cells by about 70%. A significant reduction in dye coupling was also observ ed following incubation with dopamine. Application of receptor selecti ve agonists and antagonists revealed that the uncoupling was mediated by both dopamine D1 and D2 receptors. The protein kinase A inhibitor R p-cAMPS reduced the effect of dopamine, suggesting that the neurotrans mitter regulates gap junction permeability via protein kinase A activa tion. In the presence of either forskolin, Sp-cAMPS, or dopamine, neur ons displayed a significantly higher input resistance compared to cont rol conditions. During the second postnatal week, transient applicatio n of forskolin to single neurons reversibly increased input resistance . At later developmental stages when coupling incidence had declined, this action of forskolin was no longer observed. Our data demonstrate a dependence of gap junction permeability on protein kinase A activity and on dopamine receptor activation in developing rat neocortical neu rons. These mechanisms may modulate junctional permeability during the period of circuit formation.