Purkinje Neuron Optical Activation
My secondary research topic (although first chronologically) was on the optical activation of neurons. This project resulted in 3 first-author papers that I wrote, and did all the data-analysis on – the analysis of neuronal signals is very Data Analysis intensive!
Project Description:
New chemical compounds have been developed that allow one to use light to stimulate a neuron. By optically activating the neurons while simultaneously measuring the action potential output of the neuron using traditional patch-clamp techniques, an unprecedented amount of control is given over the input/output functions of a neuronal system.
We used a unique chemical compound that can selectively switch the firing of a neuron using a combination of two different activation wavelengths. We combined this with a spatio-temporal projection system developed in our lab to control the output of “wild-type” neurons in brain slices.
I worked almost exclusively on the cerebellum, which is where over 50% of the neurons in your brain reside. In particular, I focused my attention on the Purkinje Neuron, which looks like a giant tree: receiving 150,000-200,000 inputs, and only a single output. This cell is one of the largest in the brain, and lies at the heart of the cerebellar Control System.
My research involved combining basic neuroscience ideas with advanced analysis techniques developed by electrical engineers. Specifically, we found that the Purkinje neuron can be analyzed using signal processing (Fourier analysis) and circuit diagrams. The Purkinje neuron could be described as acting as both an AM/FM signal generator, as well as a Multivibrator (non-linear) circuit. Only by using advanced mathematical analysis will we ever have a chance of understanding even the simplest of functions in our brains.
Below is an image of a cerebellar brain slice (from a rat), and a dyed Purkinje neuron that was illuminated by a specific pattern using my custom-built system.
This is an image of a rat’s cerebellum, cut in a sagital slice using a vibratome. The Cerebellum is the “back part” of a brain, and consists of circuitry controlling motor control, among other things.
Below is an image of a Purkinje Neuron, injected with Alexa dye using a patch pipette, and illuminated with UV light using a spatially controlled optical system. The neuron’s firing signal was then measured using the patch clamp.
Below is an image of what the signal from a patch-clamped Purkinje neuron looked like when photo-modulated. The photo-switchable molecule (photo-switchable Kainate receptor agonist) was “switched” using “UV” and “cyan” light. This caused the neuron to start/stop firing.
