Ayesha Azeem ’23
Parkinson’s Disease is a brain disorder that leads to shaking, stiffness, and difficulty with walking and balance. The symptoms gradually begin and get progressively worse over time. Although neuroscientists understand the role of neuron and dopamine loss in Parkison’s Disease, little is known about how dopaminergic modulation affects brain regions that are involved in the control of voluntary movement. In the primary motor cortex, which exerts control over movement execution through its central location in the motor circuit, M1 pyramidal neurons receive inputs from other cortices and the thalamus and make connections to descending motor tracts. However, the influence of dopamine on M1 excitability remains poorly understood.
Stony Brook University researchers in the Department of Neurobiology and Behavior and the Renaissance School of Medicine used an experimental model to examine the effect of acute and chronic loss of dopamine signaling on the input/output function of M1 pyramidal neurons. The researchers used patch-clamping recordings in acute brain slices of mice of both sexes using guidelines approved by the National Institutes of Health. Three methods were used to reduce dopamine signaling in order to see how motor cortex dysfunction arose: pharmacology to block motor cortex receptors, injected toxins to induce basal ganglia pathology to kill dopaminergic neurons, and the same toxins to eliminate dopamine neuron axons in the motor cortex.
Patients with Parkinson’s Disease show abnormal activity in the motor cortex, which may be due to basal ganglia pathology or the loss of direct dopaminergic innervation of the cortex. The study found that a loss of midbrain dopaminergic centers affects the ability of the M1 neurons to convert inputs into the appropriate outputs for movement. Dopaminergic signaling is crucial for voluntary movement, and reduced dopamine in the motor circuit leads to impairment of motor functions. The researchers also found that the changes in excitability because of midbrain dopamine loss rely on the synaptic drive, which may suggest that chronic dopamine loss can alter fast synaptic transmission into or within the primary motor cortex. The researchers note that future studies can focus on how the excitatory drive of M1 can be reduced through altered synaptic activity. Much is still yet to be learned about the primary motor cortex and its potential to act as an additional site of intervention to treat the symptoms of patients with Parkinson’s Disease.
 O. K. Swanson, R. Semaan, A. Maffei, Reduced dopamine signaling impacts pyramidal neuron excitability in mouse motor cortex. eNeuro 8, 1-41 (2021). doi:10.1523/ENEURO.0548-19.2021.