Dopamine Signaling

The principal mechanism for terminating dopamine signaling is reuptake by the presynaptic neuron via the dopamine transporter (DAT). Dopamine that is not taken up is metabolized by the enzymes monoamine oxidase (MAO) and catechol-O-methyl transferase... 

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Paul Greengard Physiology/Medicine Discovery of the dopamine signaling cascade... 

Thus, a GSH deficit has consequences consistent with the concept of functional disconnectivity, as hypofunction of NMDA-R and alteration of dopamine signaling have been observed. When imposed on animals during development, a GSH deficit induces also a structural disconnectivity, as revealed by the decrease in dendritic spines and parvalbumin-immunoreactivity of inhibitory intemeurons in the prefrontal cortex Finally, a transient GSH deficit during brain development causes deficits in visual recognition and olfactory integration. 

In this chapter, we undertake a review of the quantitative aspects of dopamine neurotransmission of relevance to the spatial and temporal specificity of the dopamine signal. The kinetics of dopamine release and clearance are considered in order to estimate the temporal and spatial concentration distribution of dopamine. The location of receptors and their sensitivity to dopamine are taken into account. We then consider the regulation of ion channels by the G proteins activated by dopamine, and how this might explain the effects of dopamine on the whole cell. Finally, we consider the regulation by dopamine of corticostriatal inputs to the spiny cells. 

A loosely time-locked discharge of the dopamine cell population in response to an unexpected reward would produce a phasic increase in dopamine concentration throughout the striatum. The active dopamine reuptake mechanism terminates this increase within tens of milliseconds, Thus, the phasic, reward-related dopamine signal is a... 

The postsynaptic transduction of the dopamine signal, whether steady-state, pulse increase, or the pulse decrease in concentration, depends on the relative predominance of Dl-like or D2-like dopamine receptors in the postsynaptic cell. The steady-state levels appear to be sufficient to activate both subtypes of receptor, as locally applied antagonists of either receptor subtype produce physiological effects. Two broad classes of postsynaptic effects can be identified immediate, short-term effects which reverse rapidly, and longer-term effects which persist after the removal of the dopamine signal. 

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