Professor Eric Barnard

University position

Professor

Departments

Department of Pharmacology

Email

eb247@cam.ac.uk

Home page

http://www.phar.cam.ac.uk/ri/barn... (personal home page)

Research Theme

Cellular and Molecular Neuroscience

The Cambridge Neuroscience Community

Interests

We earlier cloned the first GABA-A receptor subunits, the basis of the CNS major inhibitory pathways.We found these vary by their use of different GABA-A subtypes , by combinations drawn from 19 subunits.We have recently analysed their 19 genes in the human genome.

We are studying P2Y receptors for extracellular ATP, based upon our cloning (1993) of the P2Y1 receptor, the first of 9 subtypes.We are identifying cortex and hippocampus neurons on which certain P2Y receptors exist, and .their couplings to specific K and Ca channels ..Recently we showed that ATP is also an inducer of gene transcriptions in neurons, acting via P2Y receptors to regulate synaptic expression of genes for some effectors of ACh and glutamate neurotransmission.

We also find that P2Y receptors form dimers and are characterizing these. We are using modified fluorescence-resonance-energy-transfer confocal analysis to locate and measure such P2Y dimers in living neurons in cultures and in vivo .

A.Top row: A subset of hippocampal pyramidal neurons [shown by the neurogranin marker] co-stain for P2Y1 receptors [3 such cells in this field: all cells are shown by nuclear marker]. Middle row: Another such field, showing that P2Y1 receptors are not in the associated glial cells [GFAP marker] .Lower row: Such cells which express the P2Y1 receptor contain its sub-membranous scaffolding protein NHERF-2, which tethers it in membrane microdomains. Our own anti-P2Y1 antibody was validated by loss of all of its staining in P2Y1 knock-out mouse hippocampus. [J.Simon and E.A.Barnard,2007]. B. Similar cells, when tested first in patch-clamp recording of the M-type K+ current , show a concentration-dependent inhibition by the P2Y1 agonist ADP-βS. Responding cells were then shown to be P2Y1-positive pyramidal neurons as in panel A. [Filippov et al., J. Neurosci.,2006].
Click image to view full-size

Research Focus

Keywords

P2Y receptors

GABA-A receptors

hippocampus

FRET

channel coupling

Clinical conditions

Anxiety disorders

Cognitive impairment

Depressive disorders

Learning disabilities

Panic disorder

Equipment

Calcium imaging

Cell culture

Confocal microscopy

Electrophysiological recording techniques

Fluorescence microscopy

Fluorescence resonance energy transfer

Immunohistochemistry

Collaborators

Cambridge

Clemens Kaminski

Jennifer Nichols

United Kingdom

David Brown Web: http://www.ucl.ac.uk/Pharmac...

Richard Evans Web: http://www.le.ac.uk/cpp/

Sasha Filippov Web: http://www.ucl.ac.uk/Pharmac...

Darek Gorecki Web: http://www.port.ac.uk/departm...

International

Roy Choi Web: http://www.ust.hk/~roychoi

Satya Kunapuli Web: http://spk @temple.edu

Karl Tsim Web: http://www.ust.hk/~botsim

Yung Wong Web: http://www.ust.hk/bich/fa...

Key publications

Filippov AK, Simon J, Barnard EA, Brown DA (2010), “The scaffold protein NHERF2 determines the coupling of P2Y1 nucleotide and mGluR5 glutamate receptor to different ion channels in neurons.” J Neurosci 30(33):11068-72 Details

Siow NL, Choi RC, Xie HQ, Kong LW, Chu GK, Chan GK, Simon J, Barnard EA, Tsim KW. (2010), “ATP induces synaptic gene expressions in cortical neurons: transduction and transcription control via P2Y1 receptors.” Mol Pharmacol. Sep 16. [ Epub ahead of print ].

Choi RCY,Simon J, Tsim KWK, Barnard EA (2008), “Constitutive and agonist-induced dimerizations of the P2Y1 receptor: relationship to internalization and scaffolding. ” J Biol Chem 283,11050-11063 PDF

Filippov AK, Choi RCY, Simon J, Barnard EA, Brown DA (2006), “Activation of P2Y1 nucleotide receptors induces inhibition of the M-Type K+ current in rat hippocampal pyramidal neurons” J Neurosci 26:9340-9348

Simon J, Wakimoto H, Fujita N, Lalande M, Barnard EA (2004), “Analysis of the full set of GABA-A and Glycine receptor genes in the human genome” J Biol Chem 279:41422-41435 Details

Simon J, Filippov AK, Göransson S, Wong YH, Frelin C, Michel AD, Brown DA, Barnard EA (2002), “Characterization and channel coupling of the P2Y12 nucleotide receptor of brain capillary endothelial cells” J Biol Chem 277:31390-31400

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