The laboratory is interested in how brain disease affects communication between brain cells. In our brains, cells transfer information at specialized structures called synapses. These convert electrical signals into chemical ones that diffuse to the receiving cell where they initiate new electrical signals. Changes in the efficiency of synaptic communication and the connectivity between brain cells are believed to play a vital role in the encoding and storage of information. The most widely studied form of synaptic plasticity thought to be important for learning is that of long-term potentiation (LTP; see ref 1). LTP is an activity-dependent and a lasting increase in the efficiency of transmission at brain synapses; an example is shown on the left. Post-mortern human brain Currently, we are investigating synaptic function in Huntington's disease - a genetic disorder that affects 1-3 people per 20,000 of population.The image shows two sections of human brain, one taken from a normal patient who died of natural causes and one from a patient who died of Huntington's disease. Notice how the Huntington's diseased brain has undergone massive neurodegeneration.
Currently, there is no cure for this devastating condition. Our studies and others show that synaptic plasticity and some aspects of cell function are abnormal in early-stage Huntington's disease (refs 2,3,4). These observations are significant as they occur long before the brain starts to degenerate. If we can identify the cause(s) of these changes we will be able to design new therapies to treat this disease. To this end we are using pharmacological tools to isolate the defective proteins and molecules that give rise to abnormal synaptic plasticity and cell function in Huntington's disease. Inclusions within nuclei of hippocampal neurones.
One possible clue to the pathogenic process involved in Huntington's disease is that, in common with other neurodegenerative diseases, there is an abnormal accumulation of aberrant proteins. In Huntington's disease, these proteins aggregate to form insoluble inclusions that often precipitate within the cell nucleus, disrupting the normal processes of the cell (figure shows inclusions within nuclei of hippocampal neurones; adapted from ref 2). We are examining the relationship between the formation of inclusions and the impairment of synaptic function. In addition, we are also investigating the action of drugs that prevent inclusion formation on synaptic plasticity and cell function.
