Undergraduate Course

Department of Chemistry University of Oxford
Research Topic and Supervisor willing to supervise Chemistry Part II students.

MChem Pt II Project Description

Title: Electrochemical analysis of synaptic dopamine release in the brain

Supervisor: Professor S.J. Cragg
University Lecturer, Dept. Physiology, Anatomy & Genetics; Tutor, Christ Church
E-mail: stephanie.cragg@dpag.ox.ac.uk.
Tel: 282513
Department: Physiology, Anatomy & Genetics, Sherrington Building

Outline
Neuron-to-neuron communication in the brain occurs by the release and detection of chemical neurotransmitters. The catecholamine neurotransmitter dopamine in the brain region called the striatum is critical to how we select our actions, and to disorders such as Parkinson’s disease and addictions. However, our knowledge of the mechanisms that govern dopamine function is far from complete. New data suggest that mechanisms on axons have powerful roles in determining dopamine transmission (e.g. Threlfell et al 2012), and we need to understand such mechanisms if we are to understand dopamine function fully.

Electrochemical analytical techniques such as voltammetry, can be used in the brain to monitor neurotransmitters, notably the monoamines dopamine, noradrenaline and serotonin (Troyer et al., 2002; Phillips and Wightman, 2003). By using a microelectrode, voltammetry can detect neurotransmitter release on a timescale that parallels physiological functions (Robinson et al., 2008; Rice and Cragg, 2004). This project will use fast-scan cyclic voltammetry at carbon-fibre microelectrodes in conjunction with new technologies such as optogenetics, to monitor and explore the neurochemical mechanisms that govern the release of dopamine (e.g. Rice and Cragg 2004; Threlfell and Cragg 2006). In overview, the project will involve exploring the control of dopamine release by specific neurochemical receptors or drugs. These studies will be done in regions of the brain in which dysfunction is associated with drug addiction and Parkinson’s disease. Thus, this project should not only shed light on fundamental mechanisms of neurochemical signalling by the brain, but may also offer insights into disease.

Background references

  1. Phillips PEM, Wightman RM (2003) Critical guidelines for validation of the selectivity of in vivo chemical microsensors. Trends Anal Chem 22:509-514.
  2. Rice ME, Cragg SJ (2004) Nicotine amplifies reward-related dopamine signals in striatum. Nat Neurosci 7:583-584.
  3. Robinson DL, Hermans A, Seipel AT, Wightman RM (2008) Monitoring Rapid Chemical Communication in the Brain. Chemical Reviews 108:2554-2584.
  4. Threlfell S, Lalic T, Platt NJ, Jennings KA, Deisseroth K, Cragg SJ (2012) Striatal Dopamine Release Is Triggered by Synchronized Activity in Cholinergic Interneurons. Neuron 75:58-64.
  5. Troyer KP, Heien ML, Venton BJ, Wightman RM (2002) Neurochemistry and electroanalytical probes. Curr Opin Chem Biol 6:696-703.