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My research focuses on mechanisms of complex information processing by networks of neurons. Specifically, I am interested in mechanisms which collect primary sensory information and extract relevant features used in perception, processing and memory. Such mechanisms are particularly interesting during different behavioral states, including sleep/wake states. The primary brain structures I have chosen to study include the dorsal and ventral medulla, as they integrate autonomic information for cardio-vascular control; the hippocampus as it functions to develop spatial maps in rats, and mediates short term memory; the retina as a major preprocessing machine before visual information is passed on to the visual cortex; and the rat whisker barrel cortex as a primary sensory system that assists in navigation.
In each of the systems I mentioned, it is becoming clear that information can be encoded by the presence of synchronous, sub-threshold membrane potential oscillations that bind relevant information together through phase-coupled waveforms. The oscillatory waveforms are initiated by primary sensory input and organized in the tissue by topographic mapping of sensory space. Additionally, time and position correlated information can be encoded by phase shifts in these oscillations that depend on the delays between relevant stimuli. There is overwhelming evidence that these oscillations extend across space within neural tissue, much like standing waves in a pool of water. The propagation mechanism for these oscillations remains controversial, however there is good evidence for an extensive network of gap-junctions, since synaptic connections do not operate at the time scales observed.
The output of such systems can thus be represented by stochastic firing of cells that are positioned where colliding membrane potential oscillations sum above threshold levels. Imagine the brain as a hologram of electrical potentials, with many billions of small standing waves interacting in space and time. This theory of information processing within neural structures suggests that neural networks may really function to perform Fourier transforms of incoming information, resulting in secondary processing mechanisms that can perform complex operations in Fourier space. Such a theory also predicts that it may be possible to interpret complex information processing within neural systems using Fourier techniques.
The study of such neural mechanisms initially requires data acquisition capabilities with high temporal and spatial resolution. I have thus embarked on developing optical and electrical procedures which allow functional visualization of large neural populations in freely behaving animals, and show topographical organization of neural activity with up to 10 um spatial and 10 kHz temporal resolution. Imaging procedures allow determination of several physiological processes, including electrical potential, hemodynamics, protein, and cell membrane conformation changes. By exploiting the scattered light changes associated with neural activation, it is possible to image large areas of neural tissue with minimal and/or non-invasive procedures. In one branch of my research, I study the biophysical mechanisms involved in scattered light changes within nerves, and develop methods to optimize optical signals for practical use in isolated nerves, as well as within in-tact animal and human subjects. A significant part of my research efforts involve developing optical procedures for non-invasive neural recording within humans, as well as non-invasive imaging for diagnostic purposes.
I am currently pursuing the study of a number of systems that may process information as described above. Of particular interest is the whisker barrel cortex. Previous investigators describe simple activation of individual cortical columns (barrels) in response to whisker stimulation, however recent studies show complex interactions between barrels that encode whisker field stimulation with 400 Hz oscillatory waveforms. Another aim for the study of whisker barrels involves mechanisms for cortical reorganization of sensory fields that may depend on sleep/wake state. Dynamic imaging of the barrel field within rats during different behavioral states can answer many questions about how reorganization is modulated by sleep. Additionally, a recent study showed that harbor seals can track their prey by ultra-sensitive whisker detection of persistent aquatic vortices left by swimming objects. Modeling and emulating such a process may lead to advanced equipment for the study of hydrodynamics.
Another research interest involves the dynamic organization, development and function of spatial place cell maps within the hippocampus. Imaging procedures that I developed are well suited for recording from a large region of the hippocampus. Imaging procedures have a great advantage over fine-wire techniques that have limited spatial resolution and coverage. Imaging the spatial extent of hippocampal place cells may answer some important questions about how such place cells are organized and give us insights as to their function. Dynamic imaging of place cells within the hippocampus will also allow detailed analysis of their function across behavioral states since there is significant controversy about the role of sleep in the formation and maintenance of place cells. Imaging the hippocampus during the acquisition of other short term memories will lead to a better understanding of how such memories can be acquired.
Lastly, I am currently involved in an effort to image the function of the retina during visual processing as part of a large scale effort to develop retinal prosthesis. If a retinal prosthetic device could be developed, we need to know the correct stimulation parameters for an electrode array that could be implanted on the retinal surface for driving ganglion cells. The biophysics group at Los Alamos has developed extensive models of retinal processing, which require confirmation and fine-tuning through dynamic imaging of the in-tact retina.
In short, my research interests span a broad range of electrophysiology, biophysical processes involved in neural activation, low and high level processing of complex sensory information, and developing systems for making these measurements with high speed, multi-functional data acquisition. The neural systems I study include isolated nerve preparations from crustacean and vertebrate tissues; acute animal preparations including crayfish, lobster, frogs, rats, cats and goats; chronic animal preparations for behavioral state investigations; and non-invasive human studies. I believe such a diverse view of different tissues provides a well rounded approach to solving problems for the study of complex information processing in neural systems, and also provides a solid foundation for an exciting research program in the Neurosciences.