One Step Closer to My PhD

Yesterday I passed a milestone in my doctoral career: the first thesis committee meeting. Admittedly, this had me stressed, working hours even a doctoral student would prefer not to keep, and skipping out on a fair number of dinners, replaced by shoveling down some cold pasta over the sink in the half hour between leaving lab and hitting my mattress for the night. Though quite glad it's over, the experience wasn't all bad: in between cramming in tons of analysis on less-than-publication-worthy data and powering through review articles, I did learn a whole lot. While I don't want to overload you with the science nerd stuff, I'd like to share a bit of what I do that funds all the adventures and officially gets me the visa to live in Paris.

First off, something pretty: here are some images I've taken during experiments I ran this year.

This is an image taken using differential interference contrast. You're looking at a living slice of a mouse brain in the hippocampus. I've placed two pipettes on the brain slice: the one to the left will deliver an electric shock that will make one or more neurons fire. The one of the right is attached to the membrane of a neuron. It can record this neuron's activity. Hopefully, the neuron attached to this pipette will get a signal from one of the neurons that my first pipette will shock. If it all works, I end up with a recording of an individual neuron's response to another individual neuron's activity. (The scale bar is 20µm.)

Here is an image taken with a confocal microscope. You only see the neuron from which I want to record because my pipette is filled with a fluorescent dye. When I attach the pipette to the membrane of the neuron I want to record, this and only this neuron fills up with that dye, which lets me take an image of only the neuron from which I made a recording. (Scale bar is 20µm.)

This is another image taken with the confocal microscope. This time, I zoomed in on a few dendrites on the neuron. All those little growths you see coming out of the dendrites are called spines and they are where synapses-- connections between neurons-- are formed. (Scale bar is 5µm.)

Why do I care about these neurons? Well, it turns out that there's still a lot we don't know about how neurons communicate with each other.

The work I do is to study how an individual synapse, or a connection between two neurons, works. Inside every neuron, the signal that travels through the neuron is electric. However, neurons do not pass along electric signals from one neuron to another (most of the time). A neuronal signal gets converted from electrical to chemical when it gets passed along between neurons. There are a handful of different chemicals, called neurotransmitters, that neurons can use to send a signal. One of the most important neurotransmitters is called glutamate. I'm interested in synapses that use glutamate as their neurotransmitter. Specifically, I care about the receptors on the neuron which receives the signal, the postsynaptic neuron.

There are a few interesting things to know about these receptors:
1. There are a few kinds of glutamate receptors. My work focuses on one or two of the most important and most common, called AMPA and NMDA receptors.
2. It turns out that receptors are constantly moving around inside the synapse and even in and out of the synapse. Yes, our neurons form loads of connections--synapses-- that can last a lifetime (think of all the things you'll never forget-- your memories are stored in synapses, after all!), but even inside very stable synapses, the components of the synapse-- individual receptors-- are constantly fidgeting and are regularly replaced. In the world of people studying synapses, this was big news only a few years ago!
3. These receptors are incredibly important for your brain: if things start going wrong with these receptors, you've got a problem. Schizophrenia, alcohol and cocaine abuse, Huntington's Disease, Alzheimer's Disease, and cell death following a stroke are all linked to at least one of the two glutamate receptors I mentioned, AMPA and NMDA.

What am I trying to learn during my PhD? Well, it turns out that receptors can act differently if they are sitting at a synapse or if they're sitting somewhere else (nearby or far away) on a neuron's membrane. How? Why?? The answer is going to be way too complicated to be answered by one PhD project, but I'm hoping to contribute a little something to our understanding of just what is happening in and around the synapse.

In order to start tackling this question, I use some special chemicals which are light-sensitive and controlled by lasers. This lets me swap my neurobiologist hat for an optical engineer hat from time to time: I actually get to construct my own optical systems for controlling my chemicals. Here's my latest construction!

This is a little photo of the system of lasers, lenses, and mirrors that I've constructed. The purple line traces the path of one of my lasers, and the blue lines (with two parallel alternative paths) trace the two paths along which I can send my second laser depending on how I want to control the size of the beam of light.

Hope you made it through that! These scientific ideas and questions are pretty much my world these days, so it means a lot to take a moment to share my work. It's amazing just how personal studies become in a PhD compared to a bachelor's. You get a sense of ownership and an active role in your education during the PhD that just isn't possible during the bachelor's when you're stuck in classrooms trying to absorb all the material from all the courses required for the degree. As a PhD student I don't have to take classes anymore (even if I sometimes feel so over my head in research articles that I wish someone would just summarize them all in a course for me!). My days of written exams are over too. Preparing this presentation was my version of winter term finals season.

Having passed the PhD version of this semester's finals, I am so ready for Christmas break! Two more days of lab to go!