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Dissecting acetylcholine/glutamate co-transmission in the striatum: importance of individual neurotransmitter in addiction and movement disorders

Principal Investigator:
  • Salah El Mestikawy, Douglas Mental Health University Institute
Team Members:
  • Vania Prado, University of Western Ontario
  • Marco Prado, University of Western Ontario
  • FRSQ
  • McGill University/Douglas Hospital Research Institute
  • University of Western Ontario

Project Overview

Parkinson’s disease and addiction have tremendous human and economical costs for our society. The secret to understand these pathologies lies in unravelling the functioning of a specific brain region named striatum. The striatum regulates several behavioural outputs that are affected in Parkinson’s disease and addiction, including motor control, learning of habits and skills, motivational and reward related learning. To communicate with each other, brain cells (or neurons) use a combination of electrical and secreted chemical signals, called neurotransmitters. Amongst these brain neurotransmitters, dopamine, acetylcholine and glutamate are key players in the striatum. Dysfunction of brain communication in the striatum underlies the above mentioned pathologies. For instance, Parkinson’s disease is largely due to the progressive disappearance of dopamine from the striatum. Dopamine is also critical for reward prediction as well as addiction by drugs such as cocaine, morphine, nicotine amphetamine and, alcohol. In addition, acetylcholine-secreting neurons (also known as TANS) regulate many of the pathological alterations in these two diseases. Dr. El Mestikawy and his team have recently made the astonishing discovery that acetylcholine-secreting neurons can also release the neurotransmitter glutamate. This suggests that these neurons can communicate with other cells in the striatum using two different chemical codes. They have also uncovered evidence that these bilingual neurons may use acetylcholine to regulate habit formation and motivation, whereas glutamate regulates drug addiction. Hence, by using these two separate “languages” TANS can provide distinct forms of information to other neurons in the striatum. The final goal of our proposal is to decode how TANS, by sending these two chemical codes, regulate the striatum in health and diseased states. Understanding this “neuronal bilingualism” will lead to the refinement of medications for the treatment of striatum-related diseases.