Abnormal Climbing Fiber-Purkinje Cell Synapses

By: Sheng-Han Kuo, MD

Dr. Sheng-Han Kuo’s research team at Columbia University in New York has discovered new features in the cerebellum (pictured right) that may be caused by essential tremor, thanks to an IETF grant issued in 2014. While examining postmortem brain tissue from both essential tremor patients and otherwise healthy subjects, Dr. Kuo made a striking discovery: the degree of abnormal neuronal connections in the brain of ET patients is closely related to the tremor severity in essential tremor patients. A neuron processes and transmits information through electrical and chemical signals. It is possible these abnormal connections found in ET might be linked to tremor generation.

In a follow-up study with a larger number of brains, Dr. Kuo’s group found the link between the abnormal neuronal connections and tremor remained strong, supporting the group’s previous findings. His group found other characteristics of ET such as voice tremor also played an important role in this pathological feature. These studies have been published in the journal Brain and Neurology, respectively.

In addition, his group found a type of the supporting cell, called astrocytes, might be responsible for the damage seen in the brain of those with long-standing tremor activity. This might also explain why some people’s tremor gets worse over time. His group found astrocytes in essential tremor patients are less able to do their job of clearing away the excess chemical signals used when neurons transmit information. When the levels of chemicals get too high, they can actually be toxic to the brain, causing damage. In the face of long-standing tremor, there could be excessive neurotransmission, thus excessive damage.

Dr. Kuo’s research is very important and has several therapeutic implications. Based on his work, potential therapies could be developed that would target abnormal neuronal connections to treat tremor directly. Or we may even see the development of therapies that increase the capacity of astrocytes to clear away the unwanted neurotransmitters and stop the brain from being damaged, thus ending tremor progression.

Highlighed above, the cerebellum (Latin for “little brain”) is a region of the brain that plays an important role in motor control. The cerebellum does not initiate movement, but it contributes to the coordination, precision, and timing of movement. It receives information from the sensory systems of the spinal cord and from other parts of the brain, to create motor activity. Cerebellar damage produces disorders in fine movement, equilibrium, posture, and motor learning.