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News:
- A new manuscript, describing a phenomenon by which neurons redistribute the strength of their connections
as the size of their network scales, is
now available.
Research Approach:
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General Philosophy:
My interest is understanding the brain as an organizational memory system, and determining how computers might be built analogously.
I'm curious how brain tissue can inherently sift and weave structure from applied information, and in particular how
endogenous, biophysical properties of single neurons seem to enable the discernment, capture, and retrieval of patterns across multiple synaptic inputs.
To me this is the essence of memory architecture and a natural level at which to approach network organizing principles. |
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Novel Tools for In Vitro Physiology:
Toward this end, I am developing a 'spatiotemporal stimulator' - a computer-controlled system
of many electrodes that is capable of stimulating multiple sites of cortical tissue (acute slice or dissociated cultures) in fine patterns,
while intracellularly recording changes in synaptic activity in single neurons.
The goal is to ask, 'Are neurons sensitive to specific patterns of stimulation?
Is their plasticity tuned to specific patterns of stimulation?
What are those patterns and what do they mean?' |
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Biophysical Analysis:
To isolate the loci of synaptic change, and relate them to molecular mechanisms, I spent my Ph.D. learning as much as possible about
the biophysical analysis of single synapses, and computational modeling of synaptic and cell-wide changes.
We thus attempt incremental experiments that identify a phenomenon and then attempt to reduce it to its biophysical components.
For example, a recent paper explored a scaling phenomenon by achieving transmission across pairs of neurons, isolating that
transmission to single vesicle release, and then measuring the attenuation of the single vesicle response
by the graded application of antagonists. |
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High-Resolution Imaging:
It is becoming increasingly clear that the perturbation and measurement of neuronal circuits
will eventually be augmented or even replaced by optical methods. I have done my work so far using
high-resolution confocal microscopy, and have tried to learn the fundamentals of optics and microscopy.
I next hope to use the current time period to learn more
about computer-controlled fast-timescale imaging, in order to
1) direct laser lines for targeted spatial excitation, and
2) enable rapid sampling from computer-defined regions of interest in order
to measure distributed functional dynamics. |
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Facilitating Circuit Manipulation with Biomaterial Devices:
In vitro systems can also be controlled physically in dramatic ways to open up interesting measurements, or to directly modulate
network architecture and connectivity. Some of my work has dealt with generating and testing biomaterial devices that facilitate
such perturbations and measurements. For example, a flexible and bio-degradable electrode array was engineered to enable
chronic implantation. Similarly, a micropatterning technique was developed to define with high resolution the layout and connectivity of brain circuits on a
computer-designed chip. Being able to build custom micro-environments and micro-interfaces will allow us to take full advantage
of the experimental flexibility that in vitro systems promise. |
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Custom Electronics and Software Systems:
Finally, no matter what we are using to stimulate and record brain tissue, modern neuroscience will require advanced computer
systems and corresponding electrical hardware to drive our experimental tools. If the tools are as cutting edge as we hope,
then the ability to instantiate custom systems for their control will be an advantage. The final piece that I have strived
to achieve is therefore how to leverage an interest in computer science and electrical engineering
to repurpose EECS methods common among professionals in other fields to the study of biological network activity. |
Feel Free to Look Around:
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