PhD, Biomedical Engineering, Johns Hopkins University, 1990
|Department of Biomedical Engineering
44 Cummington Street
Boston MA 02215
(617) 353-6766 (FAX)
Director of Neuronal Dynamics Lab.
Much of my work focuses on the electrophysiological and pharmacological properties of ion channels and how these properties shape neuronal firing properties and information transmission in the mammalian brain. Other work is performed at the systems level. Electrophysiological, immunocytochemical, molecular biological, dynamical systems, and computer modeling techniques are applied. Some specific projects are listed below.
Synchrony in Heterogeneous Neuronal Networks
With collaborators Nancy Kopell and Carson Chow of the Department of Mathematics, we have examined the limitations that mild heterogeneity places on synchronization in inhibitory neuronal networks. In homogeneous networks, synchrony is stable for a wide range of frequencies. In heterogeneous networks, synchrony is disrupted at both high and low frequencies, by two distinct mechanisms. At high firing frequencies, the synaptic signal is too slow to provide adequate phasic signalling. At low frequencies, faster cells tend to shut down their slower counterparts. These results have been shown both computationally and analytically.
Cellular Oscillations in the Medial Entorhinal Cortex
Neurons of the superficial medial entorhinal cortex (MEC), which deliver neocortical input to the hippocampus, exhibit subthreshold oscillations with slow dynamics. The oscillations are intrinsic to individual neurons: they are unperturbed by manipulat ions that block synaptic transmission. Along with colleagues Angel Alonso (Montreal Neurological Institute) and Alan Kay (University of Iowa), we have studied the mechanisms underlying these oscillations electrophysiologically and computationally. These intrinsic oscillations, driven by a persistent Na+ current and a slow outward current, may help generate the theta rhythm, a slow rhythm that plays an important role in spatial learning. The number of persistent Na+ channels underlying this phenomenon is relatively small ( < 10000 ); consequently, the random behavior of these channels may contribute noise to the cellular-level response. We have examined this possibility using coordinated experiments and physiologically based stochastic models. The probabilistic nature of the Na+ channels contributes to subthreshold oscillations and higher order interspike interval statistics seen in vitro. Channel noise may shape cellular responses in vivo as well: the stochastic system has enhanced sensitivity to small periodic stimuli. These results imply that the stochastic nature of small collections of molecules have important effects at the cellular and network levels.
Neuromodulatory Properties of Zinc
Zinc is found in large amounts in the neuropil of the mammalian hippocampal formation, localized in synaptic vesicles and released under strong stimulation. Synaptically released zinc potentially regulates neuronal input-output properties via modulation of any of a number of voltage- and ligand-gated ion channels. Among these potential targets are pharmacologically unique Na+ channels that we have identified and characterized in the entorhinal cortex, the principal input structure of the hippocampal formation and a structure known to contain synaptic zinc. In the lab, we are currently conducting studies to test the hypothesis that synaptic zinc and zinc-sensitive voltage-gated channels operate together to form a novel neuromodulatory system in the hippocampal formation. Among the specific aims of these studies are to look for spatial correlations between synaptic zinc and zinc-sensitive channels, to characterize the kinetics of zinc-induced block, and to attempt to demonstrate the effects of intrinsic (rather than extrinsically applied) zinc.
Probing the Anuran Retinal Network with Pseudorandom Stimuli
The retina of the frog (Rana pipiens) has been studied for many years, but most of the network-level studies have been qualitative in nature. With collaborator David Cameron of the Boston University Department of Physiology, we have begun examining responses of retinal ganglion cells to pseudorandom, spatiotemporally complex stimuli in an effort to gain knowledge about the retina's input-output organization and computational properties.
Further information is available at the CBD ongoing research pages.
J. White, N. Kopell, M. Banks and R. Pearce (2000) Fast and slow GABAA networks of interneurons provide substrate for mixed gamma-theta rhythm, PNAS 97: 8128-8133. Addendum containing numerical methods.
Banks M.I., White, J.A., and Pearce R.A. (2000) Interactions between distinct GABAA circuits in hippocampus. Neuron 25: 449-457.
White J.A., Rubinstein J.T., and Kay A.R. (2000) Channel noise in neurons. Trends in Neurosciences 23: 131-137.
Cameron D.A., Vafai, H., and White, J.A. (1999) Analysis of dendritic arbors of native and regenerated ganglion cells in the goldfish retina. Visual Neurosci. 16: 253-262.
Lowen, S.B., Liebovitch, L., and White J.A. (1999) Fractal ion-channel behavior generates fractal firing patterns in neuronal models. Physical Review E 59: 5970-5980.
Budde T. and White J.A. (1998) The voltage-dependent conductances of neocortical layer I neurons Eur. J. Neurosci. 10: 2309-2321.
Chow C.C., White J.A., Ritt J., and Kopell N. (1998) Frequency control in heterogeneous inhibitory networks. J. Computational Neurosci. 5: 407-420.
White, J.A., Chow, C.C., Ritt, J., Soto-Trevino, C., and Kopell, N. (1998) Synchronization and oscillatory dynamics in heterogeneous, mutually inhibited neurons. J. Computational Neurosci. 5: 5-16.
White, J.A., Klink, R., Alonso, A., and Kay, A.R. (1998) Noise from voltage- gated ion channels may influence neuronal dynamics in the entorhinal cortex. J. Neurophysiol. 80: 262-269.
Budde, T., Minta, A., White, J.A., and Kay, A.R. (1997) Imaging free zinc in synaptic terminals in live hippocampal slices. Neuroscience 79: 347-358.
Chow, C.C. and White, J.A. (1996) Spontaneous action potentials due to channel fluctuations. Biophysical J. 71: 3013-3021.
White, J.A., Budde, T., and Kay, A.R. (1995) A bifurcation analysis of neural subthreshold oscillations. Biophysical J. 69: 1203-1217.
White, J.A., Alonso, A., and Kay, A.R. (1993) A heart-like Na++
current in the medial entorhinal cortex. Neuron 11: