CHEMICAL CHARACTERISATION OF SYNAPTOGENESIS
Lead Research Organisation:
Imperial College London
Department Name: Bioengineering
Abstract
Understanding the process of communication between neurones in the brain is important problem in both basic physiology and the understanding of disease. The role that neurotransmitters play during the formation of synapses is currently unknown. I intend with the use of a new type of diamond electrode (with Prof G. Swain, Michigan State University) and novel signal processing techniques (with Prof. M. Wightman, University of North Carolina) to understand the roles played by multiple co-released neurotransmitters during neuronal regeneration and synaptogenesis in culture (with Prof. N. Syed, University of Calgary). pH changes will also be measured as an indicator of vesicular release from neurones and will be used to validate the response of the diamond electrodeLong-term recordings (days) and intracellular from regenerating neurones in the intact CNS will be attempted for the first time, with Dr M. Yeoman (University of Brighton) and at Imperial CollegeThe transfer of technology between the institutions involved will help advance the means of analytical measurement in this important area and have broader technological application and consolidate my skills at the interface of analytical science, neurophysiology and engineering. The total cost of the project is 43,000.
Organisations
Publications
Bian X
(2007)
High mucosal serotonin availability in neonatal guinea pig ileum is associated with low serotonin transporter expression.
in Gastroenterology
Bitziou E
(2010)
Spatial changes in acid secretion from isolated stomach tissue using a pH-histamine sensing microarray.
in The Analyst
Bitziou E
(2008)
Simultaneous detection of pH changes and histamine release from oxyntic glands in isolated stomach.
in Analytical chemistry
Chau RM
(2009)
Determination of serotonin, melatonin and metabolites in gastrointestinal tissue using high-performance liquid chromatography with electrochemical detection.
in Biomedical chromatography : BMC
Diss L
(2016)
Acute paraquat exposure impairs colonic motility by selectively attenuating nitrergic signalling in the mouse.
in Autonomic neuroscience : basic & clinical
Leow P
(2015)
A study of the in-column detection performance for chromatography separation
in Microfluidics and Nanofluidics
Lwin A
(2010)
High performance liquid chromatography method for the detection of released purinergic and biogenic amine signaling molecules from in vitro ileum tissue
in Journal of Separation Science
MacEachern SJ
(2011)
Nitric oxide regulation of colonic epithelial ion transport: a novel role for enteric glia in the myenteric plexus.
in The Journal of physiology
Marcelli G
(2010)
Understanding changes in uptake and release of serotonin from gastrointestinal tissue using a novel electroanalytical approach.
in The Analyst
Morris R
(2016)
Electrochemical fecal pellet sensor for simultaneous real-time ex vivo detection of colonic serotonin signalling and motility.
in Scientific reports
| Description | Synaptogenesis (formation of a communication between two neurons) is mediated by low molecular weight signalling molecules including all the known transmitter types, serotonin, dopamine, nitric oxide etc. Understanding spatial and temporal variation in the release of these molecules is central to understanding neuronal regeneration and development. Isolated individual neurons from the pond snail, Lymnaea stagnalis, were used to study the role of transmitter release during synapse formation. We have developed smaller boron-doped diamond (BDD) microelectrodes and a miniature pH electrode for long-term measurements of neurotransmitters and fabricated a gold microelectrode array device to conduct multiple recordings of transmitter release. We have made advancements in utilising novel signal processing tools to conduct long term measurements of multiple transmitters. Whilst these tool for the remit of the fellowship were developed for measurements of during synaptogenesis, I have been able to utilise these methods to two core niche areas: i) detection of transmitters from the gastrointestinal (GI) tract and ii) investigation of transmitter uptake from lymphocytes and synaptosomes. Key results from all the biological studies investigated are described. |
| Exploitation Route | Understanding the role of neurotransmitters in the central nervous system and the periphery is an important challenge that will have a benefit to society, as alteration in such signalling molecules have been implicated with disease and ageing. The development of the reliable methods and devices will begin this process and have shown the ability to be utilised to investigate a host of biological problems. The impact of these new methods has been highlighted by the Royal Society of Chemistry and by web-based journals. Understanding the influence of neurotransmitter signalling during the process of synaptogenesis is an important problem in neurophysiology. The preliminary results of this fellowship will be important to fundamental neurological and biomedical problems in understanding neuronal communication and neuronal networks. Other core areas developed on monitoring and understanding neurotransmitter signalling within the gastrointestinal tract and understanding transmitter uptake from blood cells and platelets have shown to make an impact to the society. The measurements from the gastrointestinal tract will provide a functional basis to understand the function and activity of the bowel and how this alters during disease. These results are important to the fields of neuroscience, gastroenterology and clinical healthcare. The development of smaller diamond sensors and pH electrodes with new analytical methodology will provide to be useful for applications in biomedicine, environmental science and process technology. The transfer of technology from all the various institutes has been beneficial to all the groups visited. Each group benefited from skills obtained in other groups. |
| Sectors | Pharmaceuticals and Medical Biotechnology |