Metabotropic glutamate receptors in brain function

ABZProjection-of-6-12-2006-plABMAX6-12-2006-cell-full-z-s
Dr Andrew Batchelor
Senior Research Fellow
Tel: +44 (0)20 7679 0479 (x 30479)
Email: a.batchelor@ucl.ac.uk
AB1

Dr Andrew Batchelor graduated in Psychology from the University of St. Andrews before completing his PhD in Physiology from the University of Liverpool in 1993. He then moved to industry and worked for the Wellcome Foundation in Beckenham before moving to UCL in 1996. A postdoctoral position in the Wolfson Institute was followed by a Royal Society University Research Fellowship in Physiology.

My research is focussed on understanding the contribution of metabotropic glutamate receptors to synaptic function, mainly using the cerebellar cortex as a model system. I primarily use single cell electrophysiological and ion imaging techniques in acute brain slices. There are several projects active in the lab at the moment.

Post-tetanic depression

ABptd

At the parallel fibre to Purkinje cell synapse brief bursts of presynaptic activity causes suppression of subsequent glutamate release for several seconds. This appears to occur by recruitment of the post-synaptic type-1 metabotropic glutamate (mGlu1) receptor which by an as yet unclear mechanism generates a retrograde messenger which diffuses back across the synapse to influence further transmitter release. We are interested in the second-messenger pathways involved and the possible roles that this system may play in synaptic computations.

ABdagl-pathway

Presynaptic autoreceptors

At the parallel fibre to Purkinje cell synapse there are high concentrations of mGlu4 receptors present on presynaptic terminals. When activated by exogenous agonist they lead to a substantial synaptic depression however, intriguingly, there is a lack of evidence that glutamate released from the terminal can achieve the same result.

Synaptic pharmacology of mGlu receptors

Most of the pharmacological evaluation of mGlu ligands is performed with the individual receptors expressed in cell lines. We have used synaptic stimulation of mGlu receptors in their native environment to test for specificity, selectivity and efficacy of some of these compounds.

mGlu1 receptors and cerebellar learning

In collaboration with Chris Yeo in Anatomy, UCL, we are testing the hypothesis that the cerebellar-dependent form of learning known as eye-blink conditioning is stored as a mGlu1 receptor dependent form of plasticity known as long-term depression (LTD).

Neurodegeneration and neuroprotection

In collaboration with John and Giti Garthwaite at the Wolfson Institute for Biomedical Research, UCL, I have been studying various aspects of white and grey matter degeneration and protection using electrophysiological techniques.

Cerebellar calcium signals

In collaboration with Chris Richards, Physiology, UCL, we have been characterising the calcium signals in cerebellar Purkinje neurones with dual electrophysiology and 2-photon imaging.

Click here to view all publications with PDFs or doi link

Selected publications:

  • Fukunaga I., Yeo C.H. and Batchelor A.M. (2007) Potent and specific action of the mGlu1 antagonists YM-298198 and JNJ16259685 on synaptic transmission in rat cerebellar slices. British Journal of Pharmacology 151: 870-876. link
  • Fukunaga I., Yeo C.H. and Batchelor A.M. (2007) The mGlu1 antagonist CPCCOEt enhances the climbing fibre response in Purkinje neurones independently of glutamate receptors. Neuropharmacology 52: 450-458. link
  • Garthwaite G., Batchelor A.M., Goodwin D.A., Hewson A.K., Leeming K., Ahmed Z., Cuzner M.L. and Garthwaite J. (2005) Pathological implications of iNOS expression in central white matter: an ex vivo study of optic nerves from rats with experimental allergic encephalomyelitis. European Journal of Neuroscience 21: 2127-2135. link
  • Garthwaite G., Goodwin D.A., Batchelor A.M., Leeming, K. and Garthwaite J. (2002) Nitric oxide toxicity in CNS white matter: an in vitro study using rat optic nerve. Neuroscience 109: 145-155. link
  • Neale S.A., Garthwaite J. and Batchelor A.M. (2001) Metabotropic glutamate receptor subtypes modulating neurotransmission at parallel fibre-Purkije cell synapses in rat cerebellum. Neuropharmacology 41: 42-49. link
  • Neale S.A., Garthwaite J. and Batchelor A.M. (2001) mGlu receptors mediate a post-tetanic depression at parallel fibre-Purkinje cell synapse in rat cerebellum. European Journal of Neuroscience 14: 1313-1319. link
  • Lancaster B. and Batchelor A.M. (2000) Novel action of BAPTA series chelators on intrinsic K+ currents in rat hippocampal neurones. Journal of Physiology 522: 189-197. link
  • Garthwaite G., Brown G., Batchelor A.M., Goodwin D.A. and Garthwaite J. (1999) Mechanisms of ischaemic damage to central white matter: a quantitative histological analysis using rat optic nerve. Neuroscience 94:1219-1230 link
  • Vetter P., Garthwaite J. and Batchelor A.M. (1999) Regulation of synaptic transmission in the mossy fibre-granule cell pathway of rat cerebellum by metabotropic glutamate receptors. Neuropharmacology 38: 805-815 link
  • Batchelor A.M., Knöpfel T., Gasparini F. and Garthwaite J. (1997) Pharmacological characterization of synaptic transmission through mGluRs in rat cerebellar slices. Neuropharmacology 36: 401-403 link
  • Batchelor A. M. and Garthwaite J. (1997) Frequency detection and temporally dispersed synaptic signal association through a metabotropic glutamate receptor pathway. Nature 385: 74-77 link
  • Batchelor A.M., Vranesic I., Del Principe F., Garthwaite J. and Knöpfel T. (1996) The synaptic potential mediated by metabotropic glutamate receptors is not associated with a substantial elevation of cytosolic calcium concentration in Purkinje cells. NeuroReport 7: 1949-1952
  • Madge D.J. and Batchelor A.M. (1996) The metabotropic glutamate receptors. Annual Reports in Medicinal Chemistry 31: 31-40.
  • Garthwaite J. and Batchelor A.M. (1996) A biplanar slice preparation for studying cerebellar synaptic transmission. Journal of Neuroscience Methods 64: 189-197