The brain is comprised of billions of neurones which are interconnected in a complex network. The method of communication of this system is electrical in its basis. When this communication begins to break down, the result is the clinical effects seen in various neurological diseases. Using vital information gathered directly from our genetics, cell biology and biochemistry teams on the normal function and localization of PD related genes and the proteins they code for, and effect of mutations in these proteins, we can design appropriate in-depth assays to identify the consequence on neuronal communication in the brain.
In order to characterize the function of neural circuits in our PD mice, we prepare living sections of brain in thin slices. We conduct electrophysiological recordings to examine excitability and communication between brain cells in their normal setting and compare these to neurones in appropriate PD models. We can record many different parameters ranging from the measurement of the activity of groups of neurons in whole areas to assess global changes, to single neuronal recordings in order to gather knowledge about individual synapses. In addition, we employ a range of other techniques including electrochemical detection of neurotransmitter transmission, measurements of calcium signaling and dye imaging of electrical activity on a global scale. This allows us an even more in-depth look at the dysfunction leading to neurodegeneration.
These observations allow us to characterize the differences between healthy and diseased brains and design and test appropriate pharmacological agents in order to effectively reverse any changes we observe and restore normal communication. This information can then go on to be used by other teams (behavior, imaging) to further evaluate their usefulness as a therapeutic.
The subtle changes observed in our group will often far precede clinical manifestation of the disorder. Therefore, the team aims to identify these early changes and reverse them thus providing an effective preventative pre-clinical therapeutic target.