Dopamine-induced plasticity of the axonal initial segment
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2017-07-01
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en
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Dopamine is one of the principal neuromodulators in our brain, able to produce experience-dependent changes even at the earliest stages of sensory processing. Since this modulation must be fast, in order to face a rapidly-changeable environment, it does not rely on modifications of synaptic architecture of neurons, but rather on flexible and more rapid changes in ionic currents. Electrophysiological data have already revealed that dopamine modulation targets voltage-dependent Na+, K+, and Ca2+ currents, resulting in a change in neuronal excitability. However, the pathway responsible of this altered firing and the specific site of channels` expression changes are still unrevealed. Here we investigated the anatomical basis of dopamine`s modulatory action in the barrel cortex of mice, a region innervated by dopaminergic neurons and involved in processing the sensory inputs coming from the whiskers of the animal. The motor cortex and striatum, regions interacting with the barrel cortex and innervated by dopaminergic neurons as well, were investigated as well. We hypothesized that a change in ion channel distribution in the neurons could occur at the level of the axonal initial segment (AIS), a specialized compartment enriched with Na+ and K+ channels and therefore the site of action potentials initiation. The notion of the AIS as a highly plastic region is already consolidated, but whether this plasticity is involved also in dopamine modulatory action remains to be determined. Through immunohistochemistry, we first demonstrated that the AIS features significantly differ between the sub-regions investigated. Secondly, by administration of dopamine and dopamine D1/ D2 receptor on acute slices, we found significant differences between the control and the drugs conditions in multiple AIS features across all the regions investigated, with a matching pattern between barrel and correspondent motor layers. These findings suggest an involvement of AIS plasticity in dopaminergic short-term modulation, and thus in the experience-dependent changes fundamental for sensory processing.
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Faculteit der Sociale Wetenschappen