Associate Professor Yitzhak Schiller
Neurodegenerative diseases such as Parkinson’s (PD) Alzheimer’s (AD) diseases are among the greatest challenges facing modern medicine. In recent years, neurostimulation has emerged as a new treatment modality for neurodegenerative diseases. Deep brain stimulation of the basal ganglia and sub thalamic nuclei is routinely used in advanced PD patients. Moreover, cortical stimulation has recently been shown to enhance memory in humans, and as such can potentially serve to treat AD patients.
The long-term goal of this project is to develop novel neurostimulators for treatment of neurodegenerative diseases. We will concentrate on two main subjects related to neurostimulation in neurodegenerative diseases, first using closed loop stimulation paradigms, and second, implementing the optogenetic stimulation method.
- Closed-loop neurostimulation: The presently available neurostimulation paradigms use open-loop stimulation in which the stimulation protocol is predetermined and does not change according to the patient’s clinical or brain activity state. We plan to investigate closed-loop stimulation paradigms in which the electrical activity in the cortex and/or extra pyramidal structures will be recorded and the stimulation protocol will be modified according to the recorded activity state.
- Optogenetic stimulation: A new and revolutionary stimulation method has been developed recently: optogenetic stimulation. With this method, light-gated channels and ion pumps can be switched on and off using the appropriate light pulses. Optogenetic stimulation has several fundamental advantages over conventional electrical stimulation, including the ability to activate or suppress neurons, to control the duration of stimulation and apply prolonged DC like stimuli, and most importantly to target specific neuronal subpopulations.
In the proposed research, we plan to implement optogenetic stimulation paradigms for the treatment of animal models of both PD and AD. More specifically, we will attempt to ameliorate motor and cognitive symptoms in transgenic mice models of AD and PD using various activating (Channel rhodopsin-mediated) and suppressing (Helorhodopsin-mediated) optogenetic stimuli. In addition, we will specifically target different neuronal subpopulations (such as cholinergic interneurons in the putamen and globus palladium, inhibitory GABAergic interneurons in the cortex and basal ganglia, glutaminergic pyramidal neurons in the thalamus, cortex and sub thalamic nuclei and Dopamenargic neurons in the substantia nigra) with our optogenetic stimulation.