Electrophysiological characterization of abnormalities in neurotransmission in mouse models of infantile, late infantile and juvenile Batten diseases

Batten disease is a neurodegenerative disorder, neurons selectively die in different brain regions including the cortex, hippocampus, thalamus and cerebellum. However, it is still unknow why neurons are generally vulnerable in the disease, and why certain neuronal populations are selectively more vulnerable. To study the functional properties of different neuronal populations in different brain regions electrophysiology is the best approach. There are different techniques to measure the electrical activity of neurons. These include recording action potentials or transmembrane potentials with extracellular or intracellular glass electrodes, and measuring the activity of a few ion channels or recording currents flowing through the whole cell by patch clamp. Using a microelectrode array, individual action potentials and extracellular field potentials can be measured. The extracellular field potential is the extracellular signal recorded from a population of neurons that are close to a microelectrode. Microelectrode arrays (60 electrodes are standard) enable simultaneous extracellular recordings in neuronal cell cultures and brain slices from multiple sites in real time, increasing spatial resolution and thereby providing a robust measure of network activity. Using acutely isolated brain slices and a microelectrode array system from Multichannel Systems (Reutlingen, Germany) we will characterize abnormalities in neurotransmission in mouse models of Batten disease. The goal of this project is to better understand the pathomechanism of the disease forms and to identify new therapeutic targets.