Rapid dopaminergic and GABAergic modulation of calcium and voltage transients in dendrites of prefrontal cortex pyramidal neurons
Wen-Liang Zhou
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Search for more papers by this authorSrdjan D. Antic
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Search for more papers by this authorWen-Liang Zhou
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Search for more papers by this authorSrdjan D. Antic
Department of Neuroscience, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030, USA
Search for more papers by this authorKey points
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Dopamine-releasing axons make direct synaptic contacts with the dendrites of cortical pyramidal neurons. It is not known if and how dendritic physiology changes upon dopamine release at these synapses.
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We attempted to mimic synaptically released dopamine by ejecting dopamine from a micropipette. Action potential-induced voltage transients and corresponding calcium influx were both measured in thin dendritic branches using voltage-sensitive and calcium-sensitive dyes, before and after local application of dopamine or GABA.
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GABA blocked calcium influx in dendrites by blocking AP backpropagation. Dopamine, on the other hand, reduced dendritic calcium influx only at the site of dopamine release. APs successfully propagated through the dopamine application site.
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Dopamine blocked dendritic voltage-gated calcium channels in the presence of protein kinase blockers, suggesting a membrane delimited mechanism.
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Spatially restricted dopamine-mediated suppression of dendritic calcium is expected to occur during phasic dopaminergic signalling, when midbrain dopaminergic neurons respond to a salient event.
Abstract The physiological responses of dendrites to dopaminergic inputs are poorly understood and controversial. We applied dopamine on one dendritic branch while simultaneously monitoring action potentials (APs) from multiple dendrites using either calcium-sensitive dye, voltage-sensitive dye or both. Dopaminergic suppression of dendritic calcium transients was rapid (<0.5 s) and restricted to the site of dopamine application. Voltage waveforms of backpropagating APs were minimally altered in the same dendrites where dopamine was confirmed to cause large suppression of calcium signals, as determined by dual voltage and calcium imaging. The dopamine effects on dendritic calcium transients were fully mimicked by D1 agonists, partially reduced by D1 antagonist and completely insensitive to protein kinase blockade; consistent with a membrane delimited mechanism. This dopamine effect was unaltered in the presence of L-, R- and T-type calcium channel blockers. The somatic excitability (i.e. AP firing) was not affected by strong dopaminergic stimulation of dendrites. Dopamine and GABA were then sequentially applied on the same dendrite. In contrast to dopamine, the pulses of GABA prohibited AP backpropagation distally from the application site, even in neurons with natural Cl− concentration (patch pipette removed). Thus, the neocortex employs at least two distinct mechanisms (dopamine and GABA) for rapid modulation of dendritic calcium influx. The spatio-temporal pattern of dendritic calcium suppression described in this paper is expected to occur during phasic dopaminergic signalling, when midbrain dopaminergic neurons generate a transient (0.5 s) burst of APs in response to a salient event.
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