Neuroscience at HIH Home
NINDS Home NIMH Home NICHD Home NIDCD Home NEI Home NIDCR Home NIA Home NIAAA Home NIDA Home NHGRI Home NIEHS Home NCI Home
National Institutes of Health - Neuroscience at HIH Link to NIH
Link to About Us
Link to Faculty
Link to Areas of Research
Link to Seminars
Link to Interest Groups
Link to Post-doctoral Openings
Link to Home
 

Dax Hoffman, Ph.D., Investigator

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.
Photo of Dax Hoffman, Ph.D., Investigator

Staff:



Research Interests:
Activity-Dependent Trafficking of Kv4.2

Activity-Dependent Trafficking of Kv4.2

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.


Selected Recent Publications:
  • Bukalo O, Campanac E, Hoffman DA, Fields RD. (2013) Synaptic plasticity by antidromic firing during hippocampal network oscillations., Proc Natl Acad Sci U S A. 110(13), 5175-80. Full Text/Abstract

  • Lin L, Sun W, Throesch B, Kung F, Decoster JT, Berner CJ, Cheney RE, Rudy B and Hoffman DA (2013) DPP6 regulation of dendritic morphogenesis impacts hippocampal synaptic development, Nature Commun. 2013;4:2270. Full Text/Abstract

  • Campanac E, Hoffman DA. (2013) Repeated Cocaine Exposure Increases Fast-Spiking Interneuron Excitability in the Rat Medial Prefrontal Cortex., J Neurophysiol. 109(11), 2781-92. Full Text/Abstract

  • Kim E, Hoffman DA. (2012) Dynamic regulation of synaptic maturation state by voltage-gated A-type K+ channels in CA1 hippocampal pyramidal neurons., J Neurosci. 10;32(41), 14427-32. Full Text/Abstract

  • Nestor MW, Hoffman DA. (2012) Aberrant dendritic excitability: a common pathophysiology in CNS disorders affecting memory?, Mol Neurobiol. 45(3), 478-87. Full Text/Abstract

  • Murase S, Kim E, Lin L, Hoffman DA, McKay RD. (2012) Loss of signal transducer and activator of transcription 3 (STAT3) signaling during elevated activity causes vulnerability in hippocampal neurons., J Neurosci. 32(44), 15511-20. Full Text/Abstract

  • Kiselycznyk C, Hoffman DA, Holmes A. (2012) Effects of genetic deletion of the Kv4.2 voltage-gated potassium channel on murine anxiety-, fear- and stress-related behaviors., Biol Mood Anxiety Disord. 2(1):5. 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

top

Home   |   Email List   |   Search   |   Contact Us   |   Privacy Notice   |   Disclaimer   |   Accessibility
Comments or questions about the website?
Send email to neuroscience@nih.gov