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Developmental Synaptic Plasticity Section
John Isaac , Ph.D., Senior Investigator
Dr. Isaac received his B.Sc. in biochemistry with pharmacology and his Ph.D. in neuroscience from Howard Wheal's laboratory, University of Southampton UK. During his postdoctoral training in Robert Malenka's laboratory at the University of California San Francisco, he studied the mechanisms of synaptic plasticity in the hippocampus and barrel cortex. He started his own laboratory at the University of Bristol where he became Full Professor in April of 2004. In September of 2004, he joined NINDS as an Investigator and established the Developmental Synaptic Plasticity Unit. In 2007 he was promoted to senior investigator. His group studies molecular and cellular mechanisms of developmental synaptic plasticity in the hippocampus and barrel cortex.
Staff:
- Michael Ashby, Ph.D., Postdoctoral Fellow ashbym@ninds.nih.gov
- Stephanie Braud, Graduate Student brauds@ninds.nih.gov
- Jean-Sebastien Jouhanneau, Graduate Student jouhannj@ninds.nih.gov
- Daniel Kelver, Predoctoral Fellow kelverd@ninds.nih.gov
- Daiju Morita, Ph.D., Postdoctoral Fellow moritada@ninds.nih.gov
- Jong-Cheol Rah, Ph.D., Postdoctoral Fellow rahj@ninds.nih.gov
- Akira Terashima, M.D., Ph.D., Postdoctoral Fellow terashima@ninds.nih.gov
Research Interests:
Research in my laboratory primarily focuses on investigating the properties and molecular mechanisms of developmental synaptic plasticity in mammalian cortical glutamatergic synapses. Our primary approach is to use electrophysiological recordings from neurons in brain slices. This is combined with techniques such as viral expression of genes of interest in slices, 2 photon calcium imaging and glutamate uncaging. The major areas of interest are summarised below:
Developmental plasticity in the barrel cortex: We are characterising the mechanisms by which neuronal activity leads to both long-term and short-term synaptic plasticity at developing thalamocortical synapses and the role of these mechanisms in experience-dependent plasticity. In particular we are interested in the roles of pre- and postsynaptic kainate receptors in these mechanisms. The aim is to understand how these developmentally regulated synaptic mechanisms produce functioning circuits in the barrel cortex.
Molecular mechanisms of AMPA and kainate receptor trafficking in the activity-dependent regulation of synaptic strength: We are investigating the roles of proteins that interact with AMPA receptor and kainate receptor subunits in the functional regulation of these receptors. We use acute blockade of specific interactions by introducing peptides into individual neurons, or chronic over expression of constructs of interest using Sindbis virus in acute cultured hippocampal slices. In related projects in collaboration with Katherine Roche (NINDS/NIH) we are investigating the molecular determinants of kainate and NMDAR receptor subunit trafficking using electrophysiology in heterologous cells expressing mutant or chimeric receptor subunits.
Selected Publications:
- Terashima, A., Pelkey, K.A., Rah, J., Suh, Y., Roche, K.W., Collingridge, G.L., McBain, C.J. and Isaac, J.T.R. (2008) An essential role for PICK1 in NMDA receptor-dependent bidirectional synaptic plasticity, Neuron .
- Daw, M.I., Ashby, M.C. and Isaac, J.T.R (2007) Coordinated recruitment of latent fast spiking interneurons into the layer IV barrel cortex circuit enables rapid development of thalamocortical feed forward inhibition, Nature Neurosci 10, 453-461.
- Daw, M.I., Scott, H.L. and Isaac, J.T.R (2007) Developmental synaptic plasticity at the thalamocortical input to barrel cortex: mechanisms and roles, Molecular and Cellular Neuroscience 34, 493-502.
- Isaac, J.T.R., Ashby, M. and McBain, C.J (2007) The role of the GluR2 subunit in AMPA receptor function and synaptic plasticity, Neuron 54, 859-871.
- Daw, M.I., Bannister, N.J. and Isaac, J.T.R. (2006) Rapid, activity-dependent plasticity of timing precision in neonatal barrel cortex, J.Neurosci. 26, 4178-4187.
- Plant, K., Pelkey, K.A., Bortolotto, Z.A., Morita, D., Terashima, A., McBain, C.J., Collingridge, G.L. and Isaac, J.T.R. (2006) Transient incorporation of GluR2-lacking AMPA receptors during hippocampal long-term potentiation, Nature Neurosci. 9, 602-604.
- Nasu-Nishimura, Y., Hurtado, D., Braud, S., Tang, T.T., Isaac, J.T.R. and Roche, K.W. (2006) Identification of an ER-retention motif in an intracellular loop of the kainate receptor subunit KA2, J. Neurosci 26, 7014-7021.
All Selected Publications
Contact Information:
Dr. John Isaac
Developmental Synaptic Plasticity Section, NINDS
Porter Neuroscience Research Center
Building 35, Room 3C-1002
35 Convent Drive, MSC 3701
Bethesda, MD 20892-3701
Telephone: 301-451-7221 office,
301-480-1798 fax
Email: isaacj@ninds.nih.gov
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