AsianScientist (Oct. 21, 2015) – A group of scientists from Kitasato University and Niigata University has revealed that a lack of dopamine transmission through D1 receptors disturbs information flow through the ‘direct pathway’ in the basal ganglia, resulting in difficulty in initiating voluntary movements. This study was published in the journal Cerebral Cortex.
Dopamine deficiency in the basal ganglia—a collection of neurons deep in the brain—causes severe motor dysfunctions, such as slowness of movements (or bradykinesia), as observed in Parkinson’s disease. Dopamine binds D1 and D2 receptors that are expressed in the nerve cells of the striatum—a part of the basal ganglia—and exerts different effects on the nerve cells. However, how dopamine controls through these receptors the information flow in the basal ganglia and voluntary movements is still not clear.
The research team have successfully developed a novel transgenic mouse model in which dopamine D1 receptors can be reversibly reduced by a pharmacological agent, doxycycline, and found that the mice showed decreased movements when D1 receptors were reduced.
Using electrophysiological techniques in awake mice, the research team examined the electrical activity of the nerve cells in the entopeduncular nucleus (EPN), which is the output station of the basal ganglia. Normally, the electrical stimulation of the motor cortex—which resembles the electrical activity during voluntary movements—causes a triphasic response consisting of early excitation, inhibition and late excitation in the nerve cells of the EPN. The inhibition is mediated by the direct pathway and acts to initiate movements.
When D1 receptors were reduced in the transgenic mice by doxycycline, the triphasic response was changed, and the inhibition was largely decreased. These results suggest that dopamine transmission mediated by D1 receptors is essential for information flow through the direct pathway to appropriately initiate movements.
Moreover, the research team also revealed that spontaneous activity of nerve cells in the ENP did not change when D1 receptors were reduced, which is opposite of the prevalent view that a lack of D1 receptor-mediated dopamine transmission increases spontaneous nerve cell activity in the EPN. The results suggest that transient activity changes through the direct pathway—and not spontaneous activity changes—are responsible for slowness of movements in Parkinson’s disease.
“We have shown that lack of dopamine transmission via D1 receptors disrupts information flow through the ‘direct pathway’ and results in slowness of movements in Parkinson’s disease,” said study corresponding author Professor Atsushi Nambu.
“This finding provides us important clues to develop new therapies to the disease, such as on-demand activation of D1 receptors to facilitate the information flow through the ‘direct pathway’.”
The article can be found at: Chiken et al. (2015) Dopamine D1 Receptor-Mediated Transmission Maintains Information Flow Through the Cortico-Striato-Entopeduncular Direct Pathway to Release Movements.
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Source: National Institute of Natural Sciences; Photo: Shutterstock.
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