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| John Isaac , Ph.D., Senior Investigator |
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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.
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Staff:
- Michael Ashby, Ph.D., Postdoctoral Fellow ashbym@ninds.nih.gov
- Stephanie Braud, B.Sc., Graduate Student brauds@ninds.nih.gov
- Ramesh Chittajallu, Ph.D., Senior Research Fellow chittajallur@ninds.nih.gov
- Seungsoo Chung, M.D., Ph.D., Postdoctoral Fellow chungs3@ninds.nih.gov
- Jean-Sebastien Jouhanneau, Ph.D., Postdoctoral Fellow jouhannj@ninds.nih.gov
- Jose Matta, Ph.D., Postdoctoral Fellow mattaja@ninds.nih.gov
- Jong-Cheol Rah, Ph.D., Postdoctoral Fellow rahj@ninds.nih.gov
- John Sherwood, Ph.D., Postdoctoral Fellow sherwoodj@ninds.nih.gov
- Akira Terashima, M.D., Ph.D., Senior Research Fellow terashima@ninds.nih.gov
- Sherry Zhang, B.Sc., Technician zhangr22@mail.nih.gov
Research Interests:
Research in my laboratory centers around investigating the properties and synaptic mechanisms that lead to plasticity of the mammalian brain during development. These development processes are critical in ensuring appropriate wiring of neural circuits that underlie normal brain function. We use rodent brain as a model system, focusing on two regions that display remarkable plasticity, hippocampus and barrel cortex.
Hippocampal Synaptic Plasticity: The hippocampus is critical in many forms of learning /memory and long lasting modifications at hippocampal synapses are an important mechanism underlying such processes. We are investigating long-term alterations in synaptic strength at CA1 synapses. In particular, we study the molecular mechanisms by which AMPA and NMDA receptor subunits are regulated during long-term potentiation (LTP) and long-term depression(LTD), using a combination of electrophysiology, pharmacology, viral vectors and transgenic animals.
Developmental Plasticity in the Barrel Cortex: The barrel cortex in rodents is part of the somatosensory system and contains the primary representation of the facial whiskers. This system provides an excellent opportunity to understand how neuronal circuits represent information in the brain and the role of sensory experience in driving maturation of circuit function. We are interested in how changes in connectivity and synaptic function in excitatory and inhibitory circuits produces a functional network. We use electrophysiological techniques in brain slices with 2-photon imaging of neuronal structure, intracellular calcium and glutamate uncaging to map neural connectivity and synaptic function. In complementary anatomical studies, high resolution light microscopy of neurons expressing fluorescent markers is used to map barrel cortex connectivity (array tomography). Transgenic mice expressing GFP or CRE in certain neocortical layers are routinely employed to target interneurons (see image) or genetically manipulate neurons in barrel cortex. Finally, a major direction for the lab over the next few years is the development of in vivo imaging techniques and electrophysiological recordings from the barrel cortex.
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Selected Recent 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 57, 872-82.
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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