Dax Hoffman, PhD, Head, Unit on Molecular Neurophysiology and Biophysics
Ed Beck, PhD, Postdoctoral Fellow
Jinny Kim, PhD, Postdoctoral Fellow
Arrash Yazdani, BS, Biologist
Anna-Christina Bevelaqua, BS, Postbaccalaureate Fellow

A nonuniform density of subthreshold, rapidly inactivating potassium channels regulates signal propagation in the dendrites of CA1 pyramidal neurons of the hippocampus. This nonuniform distribution (with higher expression in the dendrites than in the soma) means that the electrical properties of the dendrites differ markedly from those of the soma. Incoming synaptic signals are shaped by the activity of these channels, and action potentials, once initiated in the axon, progressively decrease in amplitude as they propagate back into the dendrites. By combining patch-clamp recording in brain slices of the hippocampus with molecular biology techniques, we investigate the electrophysiological properties and molecular nature of the voltage-gated channels expressed in CA1 dendrites, how their expression is regulated, and their role in synaptic integration and plasticity.

Creation and characterization of a Kv4.2 transgenic mouse

Hoffman, Kim

We are currently characterizing a transgenic mouse expressing a dominant-negative pore mutation in the voltage-gated potassium channel subunit Kv4.2. The mouse expresses the mutant channel along with GFP under control of a tetracycline transactivator (tTA)- responsive promoter. A new line of tTA-expressing mice that limit tTA activity to the CA1 and dentate gyrus regions of the hippocampus controls expression spatially. Expression can also be controlled temporally by administration of doxycycline.

Kv4.2 trafcking in CA1 pyramidal neuron dendrites

Kim, Hoffman

Although the molecular identity of the nonuniform density of subthreshold, rapidly inactivating potassium channels found in hippocampal CA1 pyramidal neuron dendrites is not known for certain, antibody and in situ data implicate Kv4.2. Using GFP-fused Kv4.2 constructs, we are studying Kv4.2 trafficking to the dendrites.

Role of voltage-gated potassium channels in synaptic plasticity

Beck, Kim, Hoffman

Potassium channels have been shown to regulate the back-propagation of action potentials (BPAps) into CA1 dendrites. Although the functional role of BPAps is unclear at this time, it has recently been suggested that they may provide the depolarization necessary to unblock NMDA receptors, allowing for the induction of synaptic plasticity. We are currently investigating the effect of potassium channel mutations on BPAps and in the induction of LTP in organotypic slice cultures from wild-type and transgenic mice.

Hoffman DA, Sprengel R, Sakmann B. Molecular dissection of hippocampal theta-burst pairing potentiation:

Proc Natl Acad Sci USA 2002;99:7740-7745.

Watanabe S, Hoffman DA, Migliore M, Johnston D. Dendritic K+ channels contribute to spike-timing

dependent long-term potentiation in hippocampal pyramidal neurons. Proc Natl Acad Sci USA 2002;99:8366-8371.

For further information, contact hoffmand@mail.nih.gov