What lies at the intersection of math and medicine? Why many things, of course. Certainly more than could possibly fit into a blog post! But today, I am going to talk about the connection between brain function and numbers.
My name is Natalia Díaz and I am a student of Mathematical Engineering at the University of Santiago de Chile. Ever since I can remember, I have been tantalized by mathematics and medicine (especially brain function). The opportunity to mix both subjects finally arose when I entered college. That is how Neuroscience popped into my life!
To get my degree, I must complete my internship and my thesis. That’s how I started working with my mentors Dr. Patricio Rojas (University of Santiago) and Dr. Patricio Orio (University of Valparaíso). We are investigating, through numerical simulations, the effect of the electrical synapse topology between inhibitory neurons.
For this, we use a neural mathematical model of a mixed network of inhibitory and excitatory neurons of the cerebral cortex, and we study different types of topology (“all with all” or lattice style) of connection between inhibitory neurons characterizing the patterns obtained.
For example, the figure below shows a significant difference in network synchronization using different topologies. In the first yellowy-whitish graph, there is no gap junction (electrical synapse). The second shows a gap junction with a lattice topology, and in the last one we apply a gap junction with an all-to-all topology. To plot this, we use different values for the mean synaptic strength between excitatory neurons (mGsynE) and for the mean synaptic strength between inhibitory neurons (mGsynI). Lots of abbreviations, I know. But I promise they are fun!
Backyard Brains is now in its second year of interns from the University of Santiago de Chile (affectionately called Usach). Last year we had a project recording the ganglia of snails – and this we will continue our voyage in the world of invertebrates with an old favorite and a new favorite. Cockroaches and Clams.
The ElectrocardioCLAM Hi, my name is Eduardo Isla, and I am in my final year as a student of biochemistry working at both USACH and UChile (Universidad de Chile). I am completing my undergraduate thesis right now as well as working for two months at the Backyard Brains Chile office. My thesis is in a quite different area (virology) working on epitranscriptomics of HIV-2. In my spare time I like to play MMORPG games as well as explore outdoor photography.
A lot of high school students like Backyard Brains’ Neuropharmacology experiment, as you can indirectly study synaptic activity in crickets, but it is time for an upgrade. First, a little bit about neurotransmitters Did you know that neurotransmitters were discovered working on frog hearts? Everything began in 1921, when an Austrian scientist named Otto Loewi discovered the first neurotransmitter. In his experiment, he used two frog hearts. Heart 1 was still connected to the vagus nerve, and Heart 1 was placed in a chamber that was filled with Ringers solution. This chamber was connected to a second chamber that contained Heart 2. So, fluid from chamber 1 could flow into chamber 2. Electrical stimulation of the vagus nerve (which was attached to Heart 1) caused Heart 1 to slow down its heart rate. Loewi observed that after a delay, Heart 2 also slowed down. From this experiment, Loewi hypothesized that electrical stimulation of the vagus nerve released a chemical into the fluid of chamber 1 that flowed into chamber 2. He called this chemical “Vagusstoff”. We now know this chemical as the neurotransmitter called acetylcholine. It is also interesting to know English scientist Henry Hallet Dale had previously isolated acetylcholine. So, they both shared the Nobel Prize in Physiology or Medicine in 1936. For the Backyard Brains neuropharmacology upgrade I will use some Clams, yes Clams. We eat them, but they are animals too, and believe or not they have a heart. So, I’m trying to adapt Loewi’s experiments into much simpler animals, easier to access/buy and less traumatic to work on. These experiments consist of using the Backyard Brains Heart and Brain SpikerBox to make recordings of electrocardiograms on clam hearts and the effects of different compounds. For this, first of all I need to record an electrocardiogram of the heart of clams. Afterwards, I will then treat them with various compounds to attempt to alter the heart rate. I also need to ensure that the record that we actually obtain is EKG and not movement of the electrodes. In these first few days I am trying to optimize the preparation, opening the clam while keeping the cardiovascular system intact.
The Quantified RoboRoach
Hi, my name is Claudio Moreno, and I am also in my final year working at USach in the lab of Neuroscience. I am doing my thesis in ion channel physiology, studying TRPM8 channels. TRP channels are the body’s temperature transducers, and TRPM8 is responsible for the feeling of coldness. In Chile we get cranky when the temperature gets below 40 degrees Fahrenheit (I know, nothing like Michigan), and we can thank our TRPM8 channels for that.
When not studying TRPM8 channels I enjoy going playing video games and guitar. I’ve being playing guitar for 13 years and it has been one of the best things I have done to get my mind distracted during moments of high stress. I also like to travel to different cities and countries. I have travelled to many cities here on Chile (my country), and it’s really beautiful, so if you have an opportunity to come here, trust me, you won’t regret it.
The RoboRoach is one of Backyard Brains’ original inventions where you can control cockroach locomotion by electrically stimulating the antenna, but, strangely, Backyard Brains has never systematically measured the adaptation rate. Until now. To do this experiment we are doing a bunch of RoboRoach surgeries, so we can have a high enough sample size to compare sensory adaptation rate.
Once a RoboRoach is recovered from the surgery, we can start to see if we can control our RoboRoach and measure turning responses with time! And for that we built a lego tower, which has a floating ball the cockroach walks on, along with an optical mouse to read the floating ball’s movements. When the antenna neurons are activated with electrical stimuli, they will send this electrical information (called spikes) to the cockroach brain, stimulating the neural-motor reactions. The cockroach will change direction, and we can measure this change.
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This contraption allows us to measure precisely the turning of the cockroach in response to stimulation of the antenna, so we can see how it adapts over time. Now it is time to collect the data and finally say with some degree of certainty the adaptation rates across cockroaches. Like all kinds of animals with a central neural system, you can expect that neurons can adapt to a stimulus (which Backyard Brains has anecdotally observed many times in the RoboRoach). Now it is time to quantify! I am starting to get skilled at the surgery, and below you can see my first successful antenna nerve recording!
At least, that’s the idea. We’re sure the technology will catch up if we give it enough prodding and throw an intern or two its way. And hey if not? There’s still lasers, sounds like a win/win to me. Wait we don’t get lasers either? This is really going downhill fast. Apparently the higher ups don’t think beams of focused high energy photons wantonly sprayed at the brains of schoolchildren is good science.
I don’t see why anyone would have a problem with this
Ok you know what, how about beams of somewhat lower energy photons, and brains of something whose parents won’t send us more angry letters after little Johnny tattletale has another run in with the burn ward. How about LEDs and a bug? Well then.
Coming soon to a backyard near you.
And it is. Technically. So long as the mind you want to control is our tough lil buddy Drosophila Melanogaster AKA the fruit fly. And so long as the nefarious deeds you want your insatiable army of insect minions to thoughtlessly carry out is…sticking out their tongue. THEN YES. We’ve got mind control.
It’s called optogenetics, and it’s pretty crazy stuff, really. Long story short, we can stick a gene into the fruit flies that makes certain neurons, say, the sweet taste receptor Gr5a, sensitive to certain wavelengths of light-in this case, red light, because it is capable of passing through their exoskeleton into the neurons beneath. That way, if you set the little guys in front of an LED and blast away, they think the Kool Aid man just suplexed their face. And what is a fruit fly’s reaction to opening the floodgates of sugary heaven? They stick out their tongue.
It turns out you can rig up an LED with a microcontroller so that when two wires from the circuit come in contact with the fly, it completes the circuit, treating the fly as a resistor, and activates the LED. This lets us time contact with the fly to when the fly receives light (and therefore sweet-tasting) stimulation.
It might sound trivial, but there’s actually a lot to getting a response like this without any invasive action other than light stimulation. Optogenetics really opens a lot of possibilites up for experimentation that just weren’t feasible before. It took the world of neuroscience by storm just a few years ago and is on the short list for the Nobel Prize, and we‘ve got a crack team of top scientists working to bring this technology to your own backyard.
Ok, slight exaggeration again, maybe, they’re actually interns working on it. Well, an intern. But we’ve stuck him in our basement with a steady supply of mountain dew and cheetos, and if that’s not science, I don’t know what is.
I’ve just been told that in fact its not actually science. According to them, “good science” involves some sort of method, and numbers, and repeatable experimentation. Apparently blood, sweat and cheeto dust just aren’t enough for some people. We’ll have the intern fill you in on the details.