Nicotinic receptor mediated neurotransmission in the central nervous system

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The transmission of information between neurons in the brain is governed by the release of chemicals called “neurotransmitters” which bind to ion channels located on the surface of neurons. Cholinergic neurons are a class of neurons that produce and release the neurotransmitter acetylcholine. Cholinergic neurotransmission mediated by neuronal nicotinic acetylcholine receptors plays a fundamental role in enhancing cognitive function, sensory perception and motor responses. We do not yet have a clear understanding how precisely these receptors in different regions of the brain function in mediating communication between neurons. This research program will examine in detail how nicotinic receptors function in the brain using a combination of electrophysiology and a powerful new technology called optogenetics that uses blue light to activate specific neurons in the brain of mice, which were genetically engineered to express exogenous blue light gated ion channels called channelrhodopsin. We will record in the substantia nigra, a brain region important for voluntary movement, and examine in detail the plasticity of ACh release and postsynaptic nicotinic responses. We will also record from the hippocampus, a brain region important for memory, and ascertain the function of nicotinic receptors in modulating the activity of action potential propagation along axons and also whether presynaptic nicotinic receptors can facilitate glutamate release. Since nicotinic receptors are calcium permeable, nicotinic receptors fused to a genetically encoded calcium indicator (GCaMP) would allow us to monitor nicotinic receptor activity by imaging instead of performing electrophysiology. This novel technology would greatly enhance the field. Our lab has already made some nicotinic receptor-GCaMP constructs and will image their activity in neurons in brain tissue. This research will allow us to better understand the basic fundamental role of nicotinic receptors in communication between neurons in the brain and give insight how nicotinic receptor activity can control or modify certain behaviours such as movement or memory. The graduate students will acquire top-notch technical skills and mentoring necessary for the training of the next generation of scientists and professors in Canada.