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Neural Probes for Acetylcholine

Studying acetylcholine (ACh) is important for unraveling the pathophysiology of neurodegenerative diseases (Alzheimer’s disease, Parkinson’s disease), and understudying the connection between the gut microbiome and brain health. The gut microbiota can influence the central nervous system through synthesis of ACh and other neuroactive molecules.

ACh appears in the brain and body of mammalians, and is released as a messenger by the nerve cells to communicate with other nerve cells, muscle cells, and gland cells. In the brain, ACh functions both as a neuromuscular transmitter and neuromodulator, and thus plays key roles in learning and memory, motivation, and muscle control. Alterations in ACh concentration in the cerebral cortex was correlated to dementia and Alzheimer’s disease, psychiatric disorders such as schizophrenia and major depressive disorder, as well as anxiety and depression.

Because of diverse functions of ACh in the brain, in the central nervous system, and in muscle movement, a large number of anesthetic drugs and therapeutics for Alzheimer’s disease and psychiatric disorders function by interacting with cholinergic receptors. Tools for selective sensing of ACh are crucial for better understanding the role this neurotransmitter in disease progression, as well as rational design and testing of therapeutics that interact with the cholinergic receptors. ACh sensing and imaging is an emerging field which is currently in its infancy. Over 90,000 published articles address ACh, but only 12 of these have described acetylcholine sensors, and none of them is selective and sensitive enough to work directly in biological samples with the sufficient temporal resolution to study dynamics of ACh in the brain. Our research group aims to address this gap.

 

We are utilizing the unique characteristics of ACh (its permanent positive charge) and developing a new highly selective electrochemical imaging technique based on potentiometric sensing; these sensors offer selectivity and fast response times for sensing of ions in complex matrices.

We are exploring applications of these tools in studying neurotransmission, the gut-brain connection, and effect of therapeutics (for neurodegenerative diseases) on neurotransmission.

 

Related papers

ACS Sensors, 2018, 3, 12, 2581–2589.