Sooraj Shah ’24

For years, the correlation between loss of the hormone dopamine and the development of Parkinson’s Disease (PD) has been evident. Dopamine is a neurotransmitter that assists in the propagation of electrical signals in the brain, which facilitate everyday movements such as walking and writing. A reduction of dopamine levels in an individual with Parkinson’s disease may lead to shaking and poor coordination. However, the direct connection between dopamine activity and the specific regions controlling voluntary movement is yet to be uncovered. A research study directed by Arianna Maffei, a professor of neurobiology and behavior at Stony Brook University, focused on analyzing the response of primary motor cortex (M1) neurons to blockage of dopamine receptors in order to determine whether or not dopamine loss contributed to loss of voluntary movement in PD. 

In order to block dopamine receptors in the brain, a neurotoxic organic compound called 6-hydroxydopamine (6-OHDA) was injected into the M1 of mice. 6-OHDA selectively destroys dopaminergic neurons in the brain, reducing production of dopamine and allowing researchers to monitor M1 activity in the absence of dopamine. The brains were dissected two to three weeks after the procedure, and cross sections of M1 were removed. Voltage applied through the cross sections initiated action potentials, allowing for  observation of the excitatory response of the neurons. TH⁺ neurons, electrical messengers which relay messages for brain function, were counted by immunostaining the cross section, revealing cell loss in the VTA (ventral tegmental area)  of the midbrain.

The results showed that blockage of dopamine receptors in the brain leads to a reduction in M1 functionality. VTA secretes dopaminergic neurons to targets throughout the body, one of which is the primary cortex. The loss of cells in VTA would correlate to a loss of M1 function. This data was supported by measurement of rheobase, or membrane potential excitability of neurons, which was shown to be stimulated at lower rates after dopamine receptors were blocked, indicating reduced excitability of primary cortex neurons.

This study demonstrated that blockage of dopamine receptors has an effect on voluntary movement in the M1, an important first step in understanding the complexities of PD. As no known treatments of PD currently exist, Maffei believes that exploring new avenues of research surrounding the primary motor cortex may provide the best opportunity to find treatments for PD. 

Works Cited: 

[1]  O. Swanson, R. Semaan, & A. Maffei, Reduced dopamine signaling impacts pyramidal neuron excitability in mouse motor cortex. Eneuro, 8, 5 (2021). . https://doi.org/10.1523/eneuro.0548-19.2021 

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