Basic Neurobiology of Huntington’s Disease
Part 4

What happens in the brain following the onset of HD?

What are the functions of the basal ganglia?

When you look at a picture of the human brain, you’ll see that it looks gray on the outside and white on the inside. The gray matter around the outside of the brain is called the cortex. Nerve cells that make up the cortex are called cortical neurons. The cortex is divided into different parts, one of them being the motor cortex. The motor cortex is responsible for the planning and execution of body movements. Scientists have found two pathways of neural connections between the motor cortex and the basal ganglia that control the coordination of such movements. As nerve cells in the striatum of basal ganglia die under the influence of HD, both of these pathways are eventually damaged.

The Direct Pathway

The diagram below (Figure D-5) shows the direct pathway through which nerve cells communicate in sending a message from the basal ganglia to the motor cortex. As explained in more detail in the figure caption, the effect of HD on this pathway is triggered by the death of cells in the striatum. The loss of striatum cells sets off a chain of events that results in the general under-stimulation of the motor cortex. This under-stimulation from the direct pathway appears to cause the slow speed of motor movement often seen in persons with Huntington’s disease.

The Indirect Pathway

Figure D-6 shows another way that Huntington’s disease affects the motor cortex—namely, by way of the so-called indirect pathway. Once again, the death of nerve cells in the striatum has a “ripple effect” through the rest of the pathway, resulting here in the over-stimulation of the motor cortex of the brain. This over-stimulation is believed to cause the irregular, jerky movements or chorea that have long been associated with HD. In fact, HD used to be called “Huntington’s chorea” because of these effects. However, the name was changed a few years ago because some forms of the disease, especially juvenile HD, are not associated with these irregular movements.

How can the direct and indirect pathways operate at the same time, and yet have opposing effects on the stimulation of the motor cortex? The answer seems to be that there are two different types of neurons in the striatum, one for each pathway. Although both types of neurons release the same main neurotransmitter—a chemical called GABA, which figures into some aspects of HD research today—their axons run to different dendrite targets. Research shows that the neurons of the indirect pathway are generally affected first, which explains why chorea is often seen during the start of adult forms of HD. As the disease progresses, both types of striatal neurons die off, disrupting both the indirect and direct pathways and producing an overall decrease in movement. In juvenile cases of HD, both kinds of striatal neurons degenerate from the start, which is why chorea is usually not associated with juvenile HD.

Last Modified: 9-13-02

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