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Journal of Neuroscience, Vol 15, 7386-7400, Copyright © 1995 by Society for Neuroscience
Dye coupling between pyramidal neurons in developing rat prefrontal and frontal cortex is reduced by protein kinase A activation and dopamine
B Rorig, G Klausa and B Sutor
Department of Physiology, University of Munich, Germany.
During early postnatal development, lamina II/III pyramidal cells in rat
neocortex are extensively coupled via gap junctions. The factors regulating
gap junction permeability, as well as the mechanisms underlying the
developmental uncoupling process are not understood. To investigate the
influence of protein kinase A-mediated phosphorylation on dye coupling in
the developing neocortex, pyramidal cells in slices of rat 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 observed following
incubation with dopamine. Application of receptor selective agonists and
antagonists revealed that the uncoupling was mediated by both dopamine D1
and D2 receptors. The protein kinase A inhibitor Rp-cAMPS reduced the
effect of dopamine, suggesting that the neurotransmitter regulates gap
junction permeability via protein kinase A activation. In the presence of
either forskolin, Sp-cAMPS, or dopamine, neurons displayed a significantly
higher input resistance compared to control conditions. During the second
postnatal week, transient application 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 neurons. These mechanisms may modulate junctional
permeability during the period of circuit formation.
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