Epilepsy: Astrocytes and Their Role - Tom Jensen, UCL, London, UK
Hear about how epilepsy surgery provides tissue to research astrocytes! Neuroscientist Tom Jensen explains the differences between astrocytes and neurons, the challenges of using human brain tissue for research, and shares preliminary results from his studies on calcium signaling in astrocytes! Transcription and links to Tom, below! 👇🏻
Epilepsy Sparks Insights episodes are meant for informational purposes only, and not as clinical or medical advice.
Reported by Torie Robinson | Edited and produced by Carrot Cruncher Media.
Podcast
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This is a transcript and may be edited for clarity, grammar, conciseness, and readability.
00:00 Tom Jensen
“I've had this conversation with a lot of people about when people say that science is “not creative”. Generally, that's a misconception of what is being done to do science. It's almost… it’s very creative (the process of science). Designing an experiment which produces novel, kind of, insights is inherently a creative process.”
00:23 Torie Robinson
Fellow homo sapiens! My name is Torie Robinson, and wellcome to or welcome back to Epilepsy Sparks Insights. If you’re new and you haven’t done so already, please do like and comment on this episode subscribe to our channel - so to support our mission to decrease the discrimination face by and improve the quality of life of people affected by the epilepsies. And, of course (!) get everybody appreciating and getting excited about the amazing epilepsy research that is out there.
The brain tissue that is removed during surgery for epilepsy needn’t be for nothing! Today we hear all about how some of it (known as the cortex) is being used to figure out more about calcium signalling and communication; from neuroscientist and somebody with an epilepsy (!) Tom Jensen.
01:07 Tom Jensen
I'm a postdoctoral researcher working at UCL Institute of Neurology and I'm a basic neuroscientist. My research interest is on how calcium influences neuronal function. And I generally look at the level of, kind of, individual synapses. And recently we've been working on an NC3R-based funded project to study astrocytes in the brain and how astrocytes and neurons communicate with each other effectively. And we're doing this in human brain tissue from the epilepsy surgeries which are going on at National Hospital at Queen Square.
01:50 Torie Robinson
Fabulous. And just for people who aren't aware: what's the difference between an astrocyte and a “regular” (if there is such a thing!) neuron?
01:56 Tom Jensen
Yeah, so, astrocytes and neurons are a completely different kind of lineage of cells in the brain. So, neurons are the ones which do the main communication within the brain. So, the kind of rapid communication across wide scales, the things that enable your arm to move effectively.
02:12 Torie Robinson
Mm-hmm.
02:13 Tom Jensen
Astrocytes throughout the whole of the nervous system and even in the kind of enteric nervous system in your gut… have previously been thought to play a supportive role in the brain. So, they kind of work to supply nutrients and remove excessive amounts of things which would cause pathology. So, in epilepsy, they're very important for removing excitatory neurotransmitters such as glutamate from the extracellular space…
02:49 Torie Robinson
Ahh!
02:49 Tom Jensen
…to make sure that the brain cells don't get overexcited. And also, during seizures, there's a big buildup of ions called potassium ions and they make the cells even more depolarised. So, the astrocytes are really important in kind of buffering that and removing it from the brain effectively, enabling the brain to kind of terminate seizures.
03:12 Torie Robinson
So, you say this in a really lovely way. I'm just thinking, basically: astrocytes get rid of the skank, the rubbish in your brain. So, is that kind of fair?
03:19 Tom Jensen
Yeah, that's true. They also, provide a lot of energy to the neurons to allow them to work. But more importantly, I mean, in the last kind of 20 years, because techniques for measuring the function of cells have kind of evolved and we've been able to start studying other kind of processes, we've been able to actually understand now that astrocytes do a lot more than just supplying energy and removing rubbish. They're actually, an active kind of partner in communicating…
03:49 Torie Robinson
Oh!
03:50 Tom Jensen
… with neurons and between neurons. And since for the last 20 years, the concept has emerged of the tripartite synapse, where you have one cell communicating to another cell through the synapse, but then you also, have this astrocyte, which can modulate what's happening at the synapse effectively. So, the astrocytes are also, communicating themselves. They can release inhibitory or excitatory neurotransmitters; quite often this can be really important for a lot of processes in the brain, and probably including epilepsy.
04:24 Torie Robinson
So, how do you get hold of this brain tissue that you do? And because it's human brain tissue you use rather, rather than rodent, right?
04:32 Tom Jensen
Yeah, So, this is tissue, which is effectively removed - with consent, of course…
04:38 Torie Robinson
Of course!
04:38 Tom Jensen
…from the patients undergoing surgeries at the National Hospital in London. So, we use the excess tissue effectively. So, if a patient is having a temporal lobectomy to remove the sclerotic hippocampus, there's a portion of cortex which the surgeons need to remove to be able to access that area. So, for us, we're studying the cortical tissue from those regions, effectively. So, it's effectively the first bit which the surgeons can remove, not necessarily a bit which is the epileptogenic area.
The actual preparation which we make is effectively thin slice preparations which contain the circuitry - or enough of the circuitry - to be viable to use to study the physiology. But there's quite large amounts of it going to... in the Institute of Neurology, there's multiple groups working on different projects using this tissue now.
05:45 Torie Robinson
So, you can have a tissue that is taken from one surgery that is used in different labs.
05:49 Tom Jensen
Oh, for sure, yeah. And some labs might be using the hippocampus, like, I say we're using the cortex. And you can actually prepare tissue slices, which you can then culture! So, you can cut the brain slices and then keep them on a kind of membrane in an incubator. And they can last for 2 weeks, potentially. We haven't started that quite yet, but we're going that way now. So, you could then use this tissue to study the brain or to test kind of viral vectors for gene therapies and [there are] lots of purposes for it.
06:29 Torie Robinson
What are the challenges in your work? So, for instance, could it be getting enough tissue or…?
06:37 Tom Jensen
The surgeries aren't very regular…they can be quite regular. But the biggest problem is really when it comes to the sciences, effectively, we don't have a clear control - because each patient, if they're having surgery, they will be taking anti-epileptic drugs. Although we're taking tissue, which isn't necessarily pathological, it's quite possible that there could be some influence of the person's epilepsy on the structure of the tissue. Finding that kind of control and making sure everything's documented is very important for this kind of research because we need to know all the drugs, the age of the patients, and suchlike. So, that's one of the problems/drawbacks of using it. Whereas if…
07:20 Torie Robinson
It's not like you can get, you know, healthy tissue from somebody!
07:25 Tom Jensen
Well exactly, yeah!
07:25 Torie Robinson
Because they're not going to have surgery for you to access that tissue. They kind of need it for their regular life to live and be healthy.
07:33 Tom Jensen
In the tissue which we take, it has normal morphology. It looks like you would expect a normal cortical tissue to look like. You know, it's not obvious that there's not a focal cortical dysplasia or something, which obviously looks, which is pathological effectively. So, we would say it's non-pathological, but yeah, it’s difficult to know for certain that the drugs aren't having an effect on the tissue or something.
08:00 Torie Robinson
Well, how long have you been doing this, this specific work, and what are the results so, far?
08:04 Tom Jensen
I've been doing this kind of work on and off for quite a long time now. It's just we don't get tissue very, very regularly. So, I think it's coming up on kind of 10 years [that] I've occasionally been picking up a…
08:17 Torie Robinson
Oh!
08:17 Tom Jensen
… some tissue and then recording. But it's quite irregular. So, it's not part of the whole kind of research that I do. And yeah, so, we've been recording from these astrocytes and we've been recording their calcium activity. So, this is the way that astrocytes communicate effectively. So, unlike neurons, the neurons spike and you probably know that they have an electrical kind of communication.
08:43 Torie Robinson
Mm-hmm.
08:44 Tom Jensen
Astrocytes don't spike as such; they're completely electrically neutral. So, if you change their voltage, it doesn't suddenly cause a big influx of sodium ions and suchlike. They communicate by releasing calcium from their intracellular stores; so, they sense their environment and generally, when they're active, they release calcium from stores of calcium within the cell. And this goes throughout nature: all cells communicate using calcium in one way or another. It's like from conception to death: everything communicates through calcium.
09:23 Torie Robinson
Even in plants and stuff or like…
09:25 Tom Jensen
Oh, even in plants!
09:26 Torie Robinson
Yeah?!
09:27 Tom Jensen
It's that ancient. It's kind of almost every cell uses these fluctuations in calcium to encode information.
09:36 Torie Robinson
I'm gonna be looking at my garden in a different way now. It's very cool!
09:40 Tom Jensen
No, it's fascinating and we do this all through microscopy, fluorescence microscopy methods. So, what we do, effectively, is when we get these brain slices from the tissue, we use a method called patch clamp…
09:53 Torie Robinson
Oh…
09:53 Tom Jensen
…which is where you effectively get a piece of glass with a saline solution and an electrode in it to be able to record the electrical current. So, we basically, impale the cells with the glass electrode and we have a calcium-sensitive dye in the electrode that filters into the cell, and then we can study using fluorescence microscope the output of this calcium-sensitive dye. So, when there's a lot of calcium in the cell, the fluorescence increases, and we record that as a bright kind of spark on the microscope. And you can just simply watch these fluctuations in calcium through microscopy. It's quite beautiful actually. It’s actually one of the really nice things about working in this kind of field is that even at the end of the day, if your experiments have gone badly, you still have some kind of pretty picture…
10:45 Torie Robinson
Hehe.
10:45 Tom Jensen
…of a brain cell or something like that. There's a famous kind of scientist who developed a lot of these techniques (who made a lot of these fluorescent proteins) and he kind of said that one of his favourite things, his reasons for doing this was because of the colour. He loved colour.
11:04 Torie Robinson
I think most people, traditionally, don't necessarily associate neuroscience with art, right? Or things you can see visually that are beautiful.
11:11 Tom Jensen
Yeah! I mean, I've had this conversation with a lot of people about when people say that science is “not creative”. And I think that generally, that's a misconception of what is being done to do science! It's almost… it’s very creative (the process of science). Designing an experiment which produces novel, kind of, insights is inherently a creative process, I think.
11:41 Torie Robinson
So, Tom, what are the preliminary results? What are the results?
11:44 Tom Jensen
So, far… we're still not finished our work, but we're seeing some differences in the type of calcium signals which we see. It seems that they tend to last a bit longer than we were expecting from our previous work in rodent tissue. It's not a very big difference, but one of the interesting things is that the size of the responses seems to be… they seem to go over a wider area, but interestingly not a wider area in terms of the whole of the astrocyte…
12:15 Torie Robinson
Uh!
12:15 Tom Jensen
…because human astrocytes are much bigger than rodent astrocytes. Another really interesting thing is (it's been seen in some kind of old morphology work) that human astrocytes have these really long protrusions; there's two types which are a bit different to ones which we generally see in rodents. There's one at the top of the cortical layers and the real difference is that it projects a really long projection - right through all the different layers of the human cortex and that's not really seen in rodents, at least. Another one, deeper down in the cortical layers, which has these very, very fine processes, which look just like the axons of a neuron, which is very fascinating because it makes you wonder whether there's some sort of hybrid neuron astrocyte happening there, which is my kind of pet hypothesis which I’ve yet to prove!
13:13 Torie Robinson
Thank you so much to Tom - for sharing with us the cool research into astrocytes - using tissue removed during epilepsy surgery! If you’re a neuroscientist interested in aids to understand the temporal and spatial constraints of calcium imaging, check out the Interactive Calcium Dynamics Simulators which you can access - along with more information about Tom - on the website torierobinson.comwhere you can also, in addition, access the podcast, the video, and the transcription of this entire episode) all in one place. And if you haven’t already, don’t forget to like, comment, and subscribe to the channel, and share this episode with your friends/colleagues/family members/ your pet, universities, and schools - because this all supports our mission to decrease the discrimination faced by and improve the quality of life of those affected by the epilepsies… aaaaand get everyone appreciating the incredibly cool epilepsy research out there!
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Tom Jensen is a senior research fellow at UCL who’s research aims to understand how calcium-dependent signalling at small central synapses influences brain function in both health and disease. Tom uses a combination of electrophysiology and multiphoton imaging techniques to accomplish this and has a special interest in how activity dependent release of neuromodulators can control short-term synaptic plasticity and the development of epilepsy.
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