Problem Statement. Extracellular recording of the electrical activity of one or more neurons has become the method of choice in experimental neuroscience. These types of recordings, performed with an electrode positioned near an individual neuron, have characterized much of what is known about brain function. In recent decades, this technology has progressed to the point where multiple electrodes, each equipped with multiple sensors and integrated within a single microdrive device, can be lowered independently into an area of interest within the brain. Despite these advances, the process of extracellular recording remains tedious and time consuming which limits the full potential of multi-electrode and multi-sensor technology. Constant human supervision is required to command the electrode movement, continuously monitor recorded signals, assess the quality of recording, and re-adjust the electrode position to compensate for tissue migrations. A major impediment to efficient management of extracellular recording electrodes is the lack of information about the relative position and migration trends of neurons with respect to recording electrodes. Another severe shortcoming of extracellular recording technology is that very little is known about the properties of neurons whose activities are being recorded. Since properties such as size, shape and type are often linked to neuronal function, failure to separate neurons according to these parameters leads to interpretative errors.
Research Plan. Motivated by the above limitations, this proposal seeks to use advanced mathematical and engineering techniques to develop a statistical framework to estimate neuron's position, size and dendritic tree morphology (shape), based on multi-sensor measurements of neuron's extracellular potentials. The proposed framework will then be tested, first computationally, using detailed computational neuron models, and then experimentally, using animal brain slices. Theoretical and experimental comparison of their ability to estimate neuron's position, size and dendritic tree morphology, will be performed for several commercial multi-sensor recording electrodes.
Intellectual Merit. The proposed framework will enable more efficient positioning and guidance of electrodes, estimation of neuron's migration trends, and experimental separation of neurons according to their size and shape. It should be emphasized that information on position, migration trends, size and type of recorded neurons, is generally unavailable in current extracellular recording practice. The study will also lead to the development of optimal design criteria for multi-sensor recording electrodes. In summary, by bringing together ideas from engineering, mathematics, and neuroscience, this interdisciplinary research plan will fundamentally transform the way extracellular recording experiments are conducted while addressing important problems arising at the neuron-electrode interface.
Educational Plan. The central goal of the investigator?s educational plan is to devise, implement and test a educational tools and measures, designed to address the concerns engineering education in the US faces today and will face in the future. Specifically, he will enhance the educational experience of biomedical engineering students to help them better prepare for the challenges imposed by the changing global context of engineering. He will also promote engineering education and the pursuit of engineering careers in minority K-12 students and contribute to the professional development and retention of their math and science teachers.
Broader Impacts. Successful realization of the proposed research plan will place scientists in an excellent position to tackle many open questions in neuroscience, and fundamentally advance scientific understanding of the animal brain. It may also profoundly influence the design and manufacturing of multi-sensor electrodes, ultimately leading to electrodes with superior recording capabilities. Elements of the requisite study will be integrated into the teaching and mentoring of interdisciplinary engineering students, while respecting their diverse learning needs and styles. The investigator?s educational plan will also broaden the participation of underrepresented groups such as women and minorities in engineering. In addition to promoting engineering education and the pursuit of engineering careers in K-12 students, the investigator will actively participate in the professional development of K-12 math and science teachers in high-need school districts. Finally, both undergraduate and graduate students will be involved in the proposed research and educational plans. Their findings will be disseminated broadly by a timely release of data, publications, web-based materials, and digital libraries, thereby contributing to the improvement of scientific literacy in the community at large.
