Detection of phasic dopamine by D1 and D2 striatalmedium Spiny Neurons

Nair, Arun G (2017) Detection of phasic dopamine by D1 and D2 striatalmedium Spiny Neurons. The Journal of Physiology. pp. 1-25.

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Abstract

The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels,and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy ismuch higher onD2 than onD1 receptors.However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a ‘tone-sensing’ mode, allowing them to detect transient dips in basal dopamine.Overall, our results show that D2 MSNs may sense much more complex patterns of dopamine than previously thought

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 29 Nov 2017 04:00
Last Modified: 29 Nov 2017 04:00
URI: http://eprints.manipal.edu/id/eprint/150095

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