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| Dax Hoffman, Ph.D., Investigator |
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Dr. Hoffman received his B.S. in Genetics from the University of Minnesota in 1994 and his Ph.D. from Baylor College of Medicine 1999, where he studied dendritic K+ channels with Dr. Dan Johnston. During a postdoctoral fellowship with Bert Sakmann at the Max Planck Institute for Medical Research in Heidelberg Germany, he investigated synaptic plasticity and Ca2+
signaling in transgenic and gene-targeted mice. Dr. Hoffman became head of the Molecular Neurophysiology and Biophysics Unit, NICHD in 2002. His laboratory explores dendritic signal processing in CA1 pyramidal neurons of the hippocampus.
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Staff:
- Ms. Begum Choudhury, M.S., Biologist choudhuryb@mail.nih.gov
- Dr. Eu-Teum Hahm, Ph.D., Visiting Fellow hahmeute@mail.nih.gov
- Dr. Sung-Cherl Jung, Ph.D., Postdoctoral Fellow jungs@mail.nih.gov
- Dr. Lin Lin, Ph.D., Research Fellow linl@mail.nih.gov
- Mr. Wei Sun, B.Sc., Graduate Student sunwei@mail.nih.gov
Research Interests:
The dendrites of CA1 pyramidal neurons receive and process tens of thousands of excitatory and inhibitory inputs in ways that are not well understood. The presence of voltage-gated channels (active dendrites) suggests that computations are performed in dendrites, subsequent to synaptic input. Although much current and past research on synaptic plasticity in CA1 pyramidal neurons has focused on glutamate receptor regulation, relatively little is known about how voltage-gated channels influence synaptic integration. Combining patch clamp recording with imaging and molecular biology techniques, our research plan is to investigate the electrophysiological properties and molecular nature of the voltage-gated channels expressed in hippocampal dendrites. Our long-term goal is to investigate how these channels are regulated, what role they play in learning and memory and how their malfunction contributes to diseases of the hippocampus such as Alzheimer's disease and epilepsy.
To date we have focused our efforts on a particular somatodendritic voltage-gated potassium channel subunit, Kv4.2. Kv4.2 is highly expressed in CA1 dendrites and is the molecular identity of the subthreshold, rapidly inactivating (A-type) potassium current that has been shown to influence CA1 dendritic signal propagation. The large density of dendritic Kv4.2 channels acts to shape incoming synaptic signals and limit action potential backpropagation into dendrites. To assess the role of Kv4.2 channels in regulating CA1 firing properties, synaptic integration and synaptic plasticity, we have developed the means to alter functional Kv4.2 expression in cultured hippocampal neurons, in organotypic hippocampal slice cultures, and in mice. Using these tools, we have found that dendritic Kv4.2 surface expression is regulated in an activity-dependent manner, providing a new means by which Kv4.2 channels may influence synaptic function. We have also begun to characterize the mechanisms of activity dependent Kv4.2 trafficking, Kv4.2's affect on synaptic plasticity and the role of Kv4.2 auxiliary subunits in these processes.
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Selected Recent Publications:
Kim, J. and Hoffman, DA (2008) Potassium channels: Newly found players in synaptic plasticity, The Neuroscientist 14 (3), 276-286.
Full Text/Abstract
Rebecca S. Hammond, Lin Lin, Michael S. Sidorov, Andrew M. Wikenheiser, and Dax A. Hoffman (2008) Protein Kinase A Mediates Activity-Dependent Kv4.2 , The Journal of Neuroscience 28(30), 7513-7519.
Full Text/Abstract
Jinhyun Kim, Marcela Nadal, Ann M. Clemens, Matthew Baron, Sung-Cherl Jung, Yoshio Misumi, Bernardo Rudy and Dax A. Hoffman (2008) The Kv4 accessory protein DPPX is a critical regulator of membrane excitability in hippocampal CA1 pyramidal neurons, The Journal of Neurophysiology 100(4), 1835-1847.
Full Text/Abstract
Jung S-C, Kim J, and Hoffman, DA (2008) Rapid, bidirectional remodeling of synaptic NMDA receptor subunit composition by A-type K+ channel activity in hippocampal CA1 pyramidal neurons, Neuron 60(4), 657-71.
Full Text/Abstract
Kim J, Jung SC, Clemens AM, Petralia RS, Hoffman DA. (2007) Regulation of Dendritic Excitability by Activity-Dependent Trafficking of the A-Type K+ Channel subunit Kv4.2., Neuron 54(6), 933-47.
Full Text/Abstract
All Selected Publications
Contact Information:
Dr. Dax Hoffman
Molecular Neurophysiology and Biophysics Unit, NICHD, NIH
Porter Neuroscience Research Center
Building 35, Room 3C-905
35 Convent Drive, MSC 4995
Bethesda, MD 20892-4995
Telephone: (301) 402-6772 (office),
(301) 402-6772 (laboratory),
(301) 402-4777 (fax)
Email: hoffmand@mail.nih.gov
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