 In this video, I will describe the role of the cerebellum and basal nuclei in regulation of motor commands, describe how the midbrain influences the activity of the basal nuclei, and describe the pathophysiology of Parkinson's disease. The cerebellum is located just posterior to the pons, the middle region of the brain stem, and the functions of the cerebellum are important for unconscious coordination of motor commands, maintaining posture and balance. The cerebellum performs a type of learning that will store information from previous motor commands and will enable a corrective signal to be produced to fine-tune our future motor commands based on errors that we've made with previous motor commands. This is known as a feed-forward control mechanism that enables the correction of motor commands based on learning from past experiences. There are three functional regions of the cerebellum. The vestibulocerebellum receives sensory information from vestibular receptors of the inner ear that are monitoring movement of the head, and this information is important for coordinating balance and eye movements. The spinocerebellum receives sensory information from the spinal cord from proprioceptors like the raffinic corpuscles that are found in joint capsules, monitoring the position of the body, and this sensory information will be important for the cerebellum to send out involuntary commands to help maintain posture and in order to help coordinate complex movements of the body. And the cerebrocerebellum is connected to the cerebrum and receives the motor commands coming from primary motor cortex and then we'll use that input in order to generate the procedural memories and in order to develop a feed-forward control mechanism that can correct errors in our motor commands in order to fine-tune motor commands. Basal nuclei in the cerebrum contribute to motivation of motor control. They receive input from the cerebral cortex and then we'll send an input back to the cerebral cortex that will help to regulate the motivation for motor commands to come out of the cerebral cortex. Major basal nuclei that are important for regulating the motivation of motor commands include the striatum. The striatum consists of two nuclei, the caudate nucleus and the putamen. These regions receive input from the cortex and then send commands to another basal nucleus known as the globus pallidus. Globus pallidus will then regulate a pathway from the thalamus to the motor cortex providing the information that has been processed by the basal nuclei in order to regulate motivation at the level of the motor neurons in the cerebral cortex. So here we can see the network that controls motivation to initiate motor commands. The excitatory connections where glutamate is the neurotransmitter are shown in blue in the illustration whereas the inhibitory connections where the neurotransmitter is GABA are shown in red in this illustration. So the cerebral cortex motor neurons project excitatory connections into the striatum to stimulate neurons in the caudate and putamen. Then neurons in the striatum inhibit other neurons found in the globus pallidus. Then these neurons in the globus pallidus will inhibit other neurons in the thalamus and the neurons of the thalamus can stimulate the neurons of the cortex. So we can see the flowing through the stream on the left that I've just talked through is the direct pathway. The direct pathway involves the cortex stimulating the striatum. The striatum inhibiting the globus pallidus and then the globus pallidus inhibiting the thalamus. So by stimulating the inhibition of inhibition we are increasing the activity of the neurons from the thalamus that stimulate the cortex making it more likely that a motor command will be sent out from the motor cortex. On the right side we can see the pathway that's an indirect pathway through the basal nuclei where the striatum inhibits the globus pallidus and the globus pallidus that inhibits subthalamic nuclei that stimulate the globus pallidus to inhibit the thalamus. In this indirect pathway we have stimulation of inhibition of inhibition that stimulates another inhibition leading to overall a decrease activity of the neurons in the thalamus that would stimulate the cortex. Therefore increased activity of the indirect pathway makes it less likely that a motor command will be generated and sent out from motor cortex whereas increased activity of the direct pathway increases the likelihood of a motor command being sent out. There's a region of the midbrain called the substantia nigra paris compacta that produces the neurotransmitter dopamine and releases dopamine into the striatum. Dopamine has a modulatory effect in the striatum so the neurotransmitter dopamine will increase activity through the direct pathway and decrease the activity through the indirect pathway. Therefore dopamine will stimulate the direct pathway as a way of increasing the motivation to initiate motor commands. Parkinson's disease is a neurogenerative disease involving loss of the dopaminergic neurons of the substantia nigra. This leads to impaired motor control, common symptoms of Parkinson's disease include increased muscle tone and stiff rigid muscles, unwanted involuntary movements such as arresting tremor and a characteristic slow hunched shuffling walk. Studying the brains of patients that have died from Alzheimer's disease we have learned that there's a characteristic pathology in the brain known as Lewy bodies which are abnormal protein clumps found in the dopamine producing dopaminergic neurons of the substantia nigra. As the Lewy bodies accumulate in these dopaminergic neurons, dopaminergic neurons will die and this loss of dopamine input to the striatum is decreasing the activity of the direct pathway and increasing the activity of the indirect pathway which decreases the likelihood that a motor command will be initiated in the motor cortex. So it makes it more difficult to develop the motivation required to send out a motor command because the dopaminergic neurons have died. One of the treatments for Parkinson's disease is a medication known as L-dopa or levodopa. L-dopa is a chemical that is a precursor to dopamine so by providing the drug L-dopa a patient with Parkinson's disease is able to produce more dopamine even though the disease is killing the dopamine producing neurons in the brain. Taking this medication will increase the amount of dopamine that can be produced by the few dopaminergic neurons that remain in the midbrain. Another approach for the treatment of Parkinson's disease known as deep brain stimulation involves electrodes that are implanted into the basal nuclei in order to disrupt the indirect pathway helping to increase motivation to initiate motor commands.