Podcasts

Podcast – Neuronal Activity

Hosted by Dr Mike Daniels

Reading Time: 29 minutes

In this podcast Dr Mike Daniels, Postdoctoral Research Fellow in the UK Dementia Research Institute at The University of Edinburgh guests hosts a discussion with three researchers who know a great deal about Neurons – they discuss their research, lab life and mice challenges, the amyloid hypothesis, and the reproducibility.

The healthy human brain contains tens of billions of neurons—specialized cells that process and transmit information via electrical and chemical signals. They send messages between different parts of the brain, and from the brain to the muscles and organs of the body. Alzheimer’s disease disrupts this communication among neurons, resulting in loss of function and cell death.

This weeks guests are:

Dr Soraya Meftah, Postdoctoral Research Fellow in the UK Dementia Research Institute at The University of Edinburgh. Sorya explores the Neurophysiology of dementia (synaptic, neuronal, network dysfunction).

Tabitha Broadbelt, PhD Student at The University of Edinburgh. Tabitha works in the field of Behavioural Neuroscience, Learning and Memory. Specifically looking at mechanisms of learning modulation in a mouse model of amyloid pathology.

Jack Bray, PhD Student at University of Aberdeen. Jack is investigating EEG and behavioural abnormalities in preclinical mouse models of dementia (he also knows how to drive a ferry).


Click here to read a full transcript of this podcast in English

Voice Over:

Welcome to the NIHR Dementia Researcher podcast, brought to you by dementiaresearcher.nihr.ac.uk., in association with Alzheimer’s Research UK and Alzheimer’s Society. Supporting early career dementia researchers across the world.

Dr Mike Daniels:

Thank you for tuning into the Dementia Research podcast, where we discuss careers, science, and research. This week we’re going to explore neural activity and some of the great research being undertaken by our three guests. I’m Dr. Mike Daniels, and I’m delighted to be guest hosting today’s show. I’m a postdoctoral research fellow working for Dr. Barry McColl in the UK Dementia Research Institute at the University of Edinburgh. My research focuses on the role played by microglial cells and the immune system in the progression and pathogenesis of dementias such as Alzheimer’s disease. But that’s enough about me, it’s time to meet our guests. So, I am delighted to welcome Jack Bray from the University of Aberdeen, Tabitha Broadbelt, and Soraya Meftah, both from the University of Edinburgh. Hi, everyone.

Dr Soraya Meftah:

Hello.

Tabitha Broadbelt:

Hello.

Jack Bray:

Hello.

Dr Mike Daniels:

Thanks for joining us today. And let’s get started with some introductions, because we’ve already heard enough about me. Tabitha, can I start by asking you to introduce yourself?

Tabitha Broadbelt:

Hi, I’m Tabitha. I’m a third year PhD student in [Szu-Han 00:01:21] Wang’s group at the University of Edinburgh. My research has been on understanding and learning in memory impairments in a mouse model of analog pathology.

Dr Mike Daniels:

Great. Beautifully succinct. Jack, can you go next?

Jack Bray:

Yeah, sure. My name’s Jack Bray. I’m also a third year PhD student at the University of Aberdeen. I work at University of Aberdeen group studying EEG and behavioral abnormalities in different transgenic mouse models of dementia.

Dr Mike Daniels:

Great. And Soraya, can you tell us about yourself?

Dr Soraya Meftah:

I don’t know if I got the memo about being succinct. I had a little essay planned in my head. So, I’m Soraya Meftah, I’m a postdoctoral research fellow here at the UK Dementia Research Institute at the University of Edinburgh. I’m working with [Jian Gan 00:02:08] on the neurophysiology of dementias. But in my essay, I was thinking that basically I’ve been working in dementia research for nine years. So, I started out my career as a neuropathologist at Eli Lilly, which is a pharmaceutical company, which really kind of inspired me to work in dementia research. So, I then followed that on with a PhD at the university of Exeter Bristol, which brought about my love for neuroactivity. So doing kind of the neurophysiology of dementias at those universities. And so, then I’ve moved on to doing my postdoc here, doing very similar things, but in different models.

Dr Mike Daniels:

Ah, fascinating. So, I did not realize that that you worked at Eli Lilly and kind of come from the pharmaceutical route. That’s really interesting. We’re going to keep you on Soraya, because you’ve drawn the short straw. And unfortunately for you, we’re without asking about your specific research just yet. For those listeners who don’t work in neuroscience, and I’m going to say arguably me, because as a neuro immunologist, I tell all neuroscientists that I’m in an immunologist and therefore I don’t possibly know anything about neuroscience. I’m going to ask you to introduce us very broadly to the concept of neural activity.

Dr Soraya Meftah:

I was thinking about this earlier and actually I started Googling to see what the internet says, what I think it should be, and I’ve landed somewhere in the middle. So, for me, neuroactivity starts with the fact that neurons are electrically excitable cells. So, you can kind of treat neurons as electrical circuits in certain situations. So, within the brain, neurons communicate via, well using electricity. So, this can either be at the synaptic levels. So, via specialized connections between neurons, you can see small changes in electrical activity, or you can move up to the neuronal level where you see kind of larger changes, which we talk about as action potentials. Or at a kind of more zoomed out view, you can also look at groups of neurons firing action potentials, which then gives you these neuronal oscillations that people talk about. So, when we talk about neuroactivity, it’s all about the electricity of the brain and different people can look at various different resolutions. So, for example, I look at synaptic and neuronal activity. You can typically only look at that using more invasive techniques, whereas you can look at the general neuronal oscillations more kind of global activity using things like EEG, which is less invasive.

Dr Mike Daniels:

I don’t know if anyone’s got anything to add on that. The one thing I was going to ask in slight addition to that, we’re here with the Dementia Researcher podcast, and so I suppose we’re probably going to come onto this with all of your specific pieces of research, but what happens to neural activity in dementia?

Dr Soraya Meftah:

I can start on that one. Neural activity, depending on what kind of dementia model you are looking at, does very different things. So, for example, if you’re looking in models of amyloidopathy, so that’s one of the earlier pathologies we see in Alzheimer’s disease, you tend to see a hyperactivity. So, neurons are firing more action potentials, or you see these oscillations change in kind of frequency. I’m trying not to use too many complicated terms, but they get faster or slower with the way that this electrical communication is kind of occurring. So that’s for amyloidopathy. For kind of other pathologies, you can see silencing. There’s some very nice work from some of the other UK Dementia Research Institute labs that have shown that actually you get like a reduction in neuronal activity in models of telepathy, at least to my knowledge. So, you get a wide array of different brain regions doing different things. So, some will go up, some will go down. Yeah, so it’s quite a broad question.

Dr Mike Daniels:

That’s okay. Needs a lot of people to research it. And while we talking then of people’s research and what happens in [inaudible 00:06:22] in dementia, why don’t we learn a little bit about each of your specific research interests? So maybe we can start with Jack. Can you tell us about your research?

Jack Bray:

I typically work a mouse model called the RTG 4510, which is a mouse model of tauopathy. So, it has an increase in tau proteins build up in the brain over time. And this kind of model’s frontotemporal lobe dementia. So, I do is I look on a kind of global scale. Soraya mentioned looking at the EEG in these mice. One thing we’re trying to do is to kind of spot any kind of early biomarkers of the disease in these mice. So, comparing them to mice that don’t have this buildup of tau, and trying to see if there’s anything that happened specifically early in the disease, which we could then translate into the human population to try and spot the symptoms earlier than any kind of memory deficits that you may see in dementia.

Jack Bray:

My work was funded through the EQIPD Project, which stands for European Quality in Preclinical Data. And so, the aim of it is an innovative medicines initiative, which was aimed at trying to understand how we can improve the robustness and reliability of results in preclinical neuroscience. And so, as part of that project, many different sites all tried to run the same experiment in their own way. And then also we tried to harmonize the factors and ran it again to see whether we could improve the reproducibility of EEG findings across sites.

Dr Mike Daniels:

Yeah. And I guess kind of two interesting things in that is I find that the kind of biomarker field and dementia really interesting, because a lot of it is obviously about things like blood biomarkers for early detection, early diagnosis. I find it really interesting. I’ve never really considered the concept of early neural activity, essentially, changes as more of a, a kind of early detection tool. That sounds really interesting. What we’ll do is we’ll move around and just get a kind of snapshot of everyone’s research. And then maybe we can talk a little bit more broadly about maybe some of the themes that are coming out of this. So, let’s move on then to Tabitha. So, can you tell us a bit about your research?

Tabitha Broadbelt:

Yeah. I picked up on two things from Jack’s research that I think we’re kind of similar in that we’re looking at. So, I’m looking at a broader view of neural activity because I’m focusing more on the outcome, their behavior, do they remember how they learned? And also trying to look at sort of earlier markers. So, I’ve been looking into different mechanisms that modulate the learning experience, not just focusing on naive animals learning a single task, but also looking at how wider learning experience can affect their memory. So, introducing novelty, or also how a prior experience already in a task can then affect later learning. And so, to do that, I run a lot of behavioral tasks and then I pair that with pharmacological agents to look at the underlying systems. And then I follow up checking the level of amyloid pathology in the mouse model that I work with, which is the APP NLGF [inaudible 00:10:11] mice.

Dr Mike Daniels:

Another mouse model of neurodegenerative disease dementia. But this time one driven by amyloid rather than tau then, which is interesting. Let’s move on maybe, and then we can bring back, there’s a couple of things I think would be really interesting to pick up on with the two of you. And let’s finally then move to Soraya and ask you tell a little bit about your research.

Dr Soraya Meftah:

So, I think actually whilst Jack and Tabitha were talking, so for my PhD work, I was working with the same model that Jack was working with, so the TG4510 model of tau, the looking at how synaptic and neuronal dysfunction occurs at various different time points. So, I think kind of similar work, but using different techniques. So now during my post-doctoral work, I’m carrying on using a technique that I learned during my PhD, which is using NVivo whole cell patch clamp electrophysiology. And so, this basically involves recording from a single neuron within the living animal’s brain whilst it’s still alive. So, it’s a very difficult technique, very low throughput, and provides a lot of very powerful and information that we can use to try and understand synaptic dysfunction in the kind of intact system along with neuronal dysfunction as well. And I’m doing that currently in the APP P S1 mouse model of amyloidopathy. So that’s also where I was laughing because between the two, I’ve kind of done the tauopathy and now I’m doing amyloidopathy. But we’ll probably move on some other models as well in the near future.

Dr Mike Daniels:

So, we’ve got people using three different mouse models, but Soraya spanning both of the mouse kind of themes that the other two work, and also, we’ve got from the single cell neuroactivity recording, up to the whole brain, the EEG. And then finally to Tabitha with kind of what the effect of that different neuroactivity on the behavior is. So, it’s some pretty slick curating of panelists, I would say, on this Dementia Researcher podcast. Speaking of what we’ve been talking about, I guess a little bit briefly in terms of animals, and this is something that obviously might be a little bit biased because all three of you do a lot of your research on mice. And also, I personally do a lot of my research on mice. But I suppose there are definitely upsides and downsides to neural activity in dementia in mice.

Dr Mike Daniels:

So can anyone come in on how similar the changes, no matter what mouse model you use, how similar the changes in neural activity in dementia are between the … Or maybe Tabitha probably better the behavior potentially. So, each of your individual expertise, how similar they are in the mouse model versus in humans, or if it’s not known, which bits of it aren’t known. And tell you what, I’ll go around you and apologies in advance everyone because I actually didn’t prepare any of the panelists at this question. I’ve come up with this entirely in advance. So, I’ve given them a very little chance here. But Jack, how much do we see change in your mouse model versus what we know changes in humans that live with dementia?

Jack Bray:

Well, one of the main symptoms, I guess of neuroactivity in human patients would be termed a kind of classical slowing of the EEG. So essentially all of the activity shifts into kind of lower frequencies. As mentioned before, with certain models, you do see times they’re slowing, or sometimes even with some of the APP models, you do see a kind of a shift to the higher frequency, so a faster newer activity, I guess. And this is, I guess, one of the big issues with kind of preclinical translational research, is that we are working with models of the disease and not obviously the disease itself. So personally, in the TG4510 models, we do see a kind of a slowing of the EEG, which is quite nice, quite translatable. But again, it’s only kind of modeling the tau pathology. And as we know, typically we kind of get amyloid and tau pathology both in the buildup in the human population.

Dr Mike Daniels:

Yeah, and obviously you’re only modeling essentially the genetic, even if you were modeling a human disease, you’re modeling the kind of 1% genetic size.

Jack Bray:

Yeah, the familial side of things.

Dr Mike Daniels:

Which again, is a caveat that we all take on board when we do this kind of research. So that’s really interesting. So, let’s go around in the same order that we went in before. And then come up to Tabitha, if you’ve got any kind of insight into the sort of behavioral changes, maybe the early changes that you were kind of alluding to earlier, you see in the mice, and whether that relates to what we see in humans.

Tabitha Broadbelt:

I’ll touch upon something that Jack mentioned before, which is the difficulty in translating from the models that we have into the humans. And I think for behavior, there is a particular point where a lot of the research that is done with Alzheimer’s patients, you can ask some questions, they check a lot of their episodic memory. Do you know what year it is, where you are? And unfortunately, it’s a lot harder to ask a mouse to answer that. So, translatability, you have to get a little bit more creative and try and see if they remember where they’ve placed certain objects or where they’ve seen it before, and if they remember being in this environment before. So, to answer Jack, I’m also sort of only amyloid, so I’m only guessing that pre-clinical aspect. And I think what we see with a lot of the amyloid models is it takes a while and quite strong pathology to start then seeing the same kind of behavioral memory impairments that you would then translate to patients with Alzheimer’s, so that loss of being able to remember what you’ve seen before.

Dr Mike Daniels:

And is that like as a specific example of the sort of things that you do, you have mice, and you asked them to remember where they put something?

Tabitha Broadbelt:

Yes. So, one of the tasks that I did, which is very fun, its full name is the appetite of delayed matching to place task. I always called it the Cheerio task because that is what the mice have to search for is a small piece of Cheerio that’s hidden in a sand well, which is within a large arena. And then every day we give them a new location where to find this Cheerio reward, which is sort of similar to the kind of everyday spatial memory tasks that an Alzheimer’s patient might need to do. Where have I put my keys today, where is the Cheerio hidden today? And then we make it a little bit harder for them and give them some decoy wells to check if they’re properly remembered or if they’re just digging everywhere.

Dr Mike Daniels:

And so, then to kind of finally round us off then in terms of asking about how everyone’s individual research on maybe amyloid or mouse models of dementia relates to what we see in humans in the context of neural activity, Soraya, what do you see in your mouse models and how does that relate, and how much do we know about it?

Dr Soraya Meftah:

So, I think I’m going to start with a little anecdote that I forgot to say at the start. So, when we can think of neural activity, you can kind of imagine a football stadium. So, if you were standing outside the football stadium with a microphone, that would roughly be similar to what EEG is and the supporters are going to be our neurons. So, if you wanted to listen to what each individual person is saying, you wouldn’t have a chance of hearing it. Whereas you could probably hear when a goal was scored or some other kind of large-scale events. So, we can look at EEG in patients and you get a rough idea of some of the larger events or the kind of when a person’s thinking, their oscillations look like this. But in humans, we really can’t look at the underlying individual single cell activity, and even more so the synaptic activity, because it’s such a kind of fine resolution.

Dr Soraya Meftah:

Well, you can look at neuronal activity, but it’s only in epilepsy patients, for example, where it’s a super invasive procedure, and it’s not going to be anywhere close to being used in dementia. So, I guess at my level, I see various different changes in kind of synaptic transmission neuronal activity in general. I could talk about various different [inaudible 00:19:33], but I won’t. But we don’t really know how that would relate to the human condition exactly because we can’t measure it in human patients. So, we can kind of infer that perhaps this hyperactivity or this slowing then leads to these EEG changes that Jack’s seeing and that we see in the patients. And that’s of the link that I’m starting to work on is what is the actual individual neuronal synaptic correlates that then perhaps underpin these changes in the kind of oscillations EEG activity that we can measure. So, my stuff’s all inferred, but very difficult to measure in humans.

Dr Mike Daniels:

Yeah, that’s really, I love that. That analogy is great. I’m going to have to borrow that if I ever talk about bulk versus single cell RNA sequencing. It’s a kind of similar concept, I guess, of like, I love that. Yeah, when a goal is scored, like that’s when everything’s in sync and everyone gets louder and then you see it. But I guess if you had your equal home and away fans and a goal was scored on one end, then half of them would get quieter, and the other half would get louder. And the actual signal might not change. Maybe you wouldn’t even know, depends how rubbish the fans are. Don’t [inaudible 00:20:47] castle up here at hearts, I’ll tell you that. I don’t know if we’re allowed to-

Dr Soraya Meftah:

I was going to say, that’s a Scotland reference, but-

Dr Mike Daniels:

Particular, very, very local references, Edinburgh references. That’s brilliant. So, we’ve talked then about the way that each of our individual pieces of research link to changes in neural activity in both mice and versus humans. And I wanted to know kind of go back a little bit and pick up on something that Jack mentioned as part of his research. And that’s the kind of reproducibility side of it. And I think that’s really interesting and super important. And I wasn’t aware of kind of quite how much there is in terms of getting this sort of stuff off the ground, because on the face of it, you maybe don’t get any exciting new results if all you do is say, “Hey, we see the same thing and guess what? We see it in five different places in five different countries.”

Dr Mike Daniels:

But how important is that? Like is it worth looking at if you don’t see it in five different places in of different countries? So, I don’t know. Jack, I don’t know what your experience has been with this kind of cross site reproducibility aspect of it. Like have you been able to get things more reproducible and what’s your overall view on reproducibility in your field? Is it improving? Is it in a relatively good state? What’s your thoughts?

Jack Bray:

Yeah. I mean, obviously reproducibility is kind of a massive topic for science. If something isn’t reproducible, then there’s a serious doubt cast upon whether it’s an actual statistically significant finding or that kind of thing. So, my kind of project stemmed from a couple years ago, there was lots of publications about the lack of reproducibility in science in general. And I think there was up to kind of 75% of researchers had failed to reproduce a scientific finding. And that’s not really specific to neuroscience, preclinical neuroscience, it’s kind of across the board. So, it’s obviously something we really need to kind of take on board that we should be kind of able to reproduce things, specifically with our kind of EEG side of the reproducibility debate. We actually found that in general, the robustness and reproducibility of EEG findings was quite good.

Jack Bray:

The main factors involved, I guess, is that there’s no kind of standard EEG recording device. There are no standard electrodes, there’s no standard analysis tools. Everything is kind of idiosyncratic to each lap. That’s, we think, is where the majority of the irreducibility comes from. But yeah, certainly one of the biggest factors we found to improve reproducibility within science or preclinical neuroscience is mainly on the reporting side. Obviously it’s very hard to reproduce a study if you’re missing some key factors of that study and even still kind of reading papers that people will not report even something as big as like the sex of the animal you used, or the time of day of the experiment, or recording device used, or even like the color of the maze used. These things all do have an effect on the outcome of the results.

Jack Bray:

And so, it’s really down to the researchers to publish all the pertinent information so that someone else could reproduce it if possible. One of the issues is that the publication bias. Essentially what that means is that it’s very hard to publish a negative or a null result. You kind of need a statistically significant finding in other to get published. So, this, as you were mentioning, it’s very hard to, to even publish reproducibility studies because it’s not going to be like … Yeah, except in journals because it’s not interesting enough. And that I think is one of the big issues and the strives the kind of reproducibility debate

Dr Mike Daniels:

Yeah. And I suppose we hope that things like having performers when you submit your paper, like you have to give all your methods in the detail and you would hope, I suppose, that when things go to publication, the reviewers say you haven’t given enough detail on your methods. We could do plenty of podcasts on issues of publication, I’m sure. But I don’t know whether, because obviously reproducibility is by no means something that’s confined to EEG research and mouse models. And like you were kind of alluding to with things that can obviously be particularly sensitive to that sort of thing is things like behavior and things like your color of your maze and the time of day and things like that, very, very sensitive readouts. I don’t know if tab Tabitha, if you’ve got any experience with what you think reproducibility in behavior is like. Are there any tips for anybody that’s doing a lot of behavior research, seeing as that’s your expertise in making sure you can do robust and reproducible studies?

Tabitha Broadbelt:

Yeah, I do have a tip, which is that if they haven’t put the information in their paper, then go ask them. Or if you see someone doing a similar task to you at a conference they’re posted, do go and ask them how they run it because there will always be so many different variables that they won’t talk about or they won’t have thought that other labs would do differently. And that’s definitely, I think is one of the challenges in doing behavioral work because each mouse is individual, so you always get a fair amount variability within your experiments. And then it’s just a case of trying to optimize the experimental procedures for even tiny details such as how you hold the mice, how you handle the mice, that’s often not put in the papers. And yeah, I think that’s definitely a struggle in trying to reproduce behavior experiments, is that we’re maybe not quite getting to the level of detail that we need to share with other researchers to help them reproduce our results.

Dr Mike Daniels:

Is there anything that Soraya can add to that?

Dr Soraya Meftah:

I just wanted to add a little anecdote because the other day, Tabitha and I were talking about, I think behavioral reproducibility or something like that, and she was saying that one of her colleagues would hum the same song because she started humming that song the first time, she did that experiment. But I think it’s the same with electrophysiology experiments as well, and other ones, we’re all very superstitious. So, for me, I only wear certain necklaces by my rig and there are certain kind of quirks that maybe doesn’t affect anything, but maybe it does. Maybe the song that you sing when you get in gives you a different mood when you’re going into the room, which therefore means you handle the mice better, or I approach my cell with more care or something. So, there’s a lot of other little things that I think could affect reproducibility. But I thought whilst we’re on that topic, I should add that in.

Dr Mike Daniels:

You should maybe stick to evidence-based reproducibility. I always thought we, and I’m now going to go slightly off topic, but we can come back on. It’s not really off topic, its reproducibility based, but it wasn’t what I was going to say before. But if something is so sensitive that you have to do it in a very precise way, in a very precise time, for example, you have to use the same equipment to read out. If you change your piece of equipment and you no longer see that effect, is the effect important enough for us to be studying? This is always my question with this, because my students will say, “Ah, go do this exactly the same way.”

Dr Mike Daniels:

And I like to think that we should be researching things that are so stonking and robust, that it doesn’t matter how you do it. Like you will still see that effect. And I know that this caveats a time of day, especially if you’re working on something circadian, and could totally not see an effect at different times of day. But I always think there is an aspect of like, if you only see it when you fix every, every other tiny, independent variable, is it that important? I don’t know if anyone’s got any comments on that. Yeah, Tabitha.

Tabitha Broadbelt:

Yeah. I was going to comment purely from the mind point of view, is that obviously they don’t have a lot of novelty that happens in their lives, that you have to be careful that you don’t know what you’re doing and how that might be being perceived by them. But yeah, I do agree. There is a certain robustness.

Dr Mike Daniels:

That’s a really good point, [crosstalk 00:30:18] because I suppose what I might say in that monologue is like, oh, I’m wearing the same perfume every day if you have to do such a minor thing as that. But to a mouse, the same perfume every day is probably the equivalent of somebody dumping a bin truck in your bedroom every morning. And you would probably have a very different day if somebody dumped a bin your bedroom every morning. So that’s a really good point. That put me in my place.

Dr Soraya Meftah:

I was also going to add, I did see something recently where different experimenters were doing single cell electrophysiology recordings and the different experimenters, I think had statistically significant different results. But the result overall was the same if that makes sense. So perhaps it was slightly lower or slightly higher, but actually the two experimenters were different from each other. And they were using the same equipment and the same lab, et cetera, et cetera. But different people do things differently so it’s kind of hard to narrow down those little changes.

Dr Mike Daniels:

Okay we’ll go back to the thing that I was going to talk about just before I went off topic slightly. And we were starting to talk about advice and tips for people. And being that a lot of the listeners on this podcast will be early career researchers that might be kind of undergraduate or masters or maybe early PhD stage. And we’re, on this podcast, really lucky to have three people that are either coming towards an end of a PhD or even have finished it. So, I was hoping to get from you, some kind of top tips. And they can be specifically about your research about the kind of things that you do, for example, when Tabitha was talking about the behavior. Or actually just anything to someone starting a PhD, maybe in dementia research, and probably I say maybe specifically in doing this sort of thing. But as I said, anything general will also be extremely useful. So, we’ll go around in the order we have been going in and we went in before. So, we’ll start with you, Jack.

Jack Bray:

My main kind of tip would be no one knows everything. Sometimes I feel a bit silly asking for help or for advice on something. It may show that I don’t know it, so maybe I should just do the research and find out for myself. But I think one of the biggest things I’ve learned is that asking for help is more valuable than kind of just trying to figure out on your own. Yeah, definitely asking for help, seeking advice from people who have been there before or who are doing a similar thing is definitely super valuable, I would say

Dr Mike Daniels:

And Tabitha.

Tabitha Broadbelt:

Yeah. So, it was similar thing. Don’t be afraid to go up to people and talk about what you are doing or about what they’re doing. I found that most people, whether they’re PIs or the admin staff are always really happy to help where they can or direct you to where they think you’ll be able to get more help and advice. A lot of postdocs, love the postdocs. They’re the best. But yeah, generally people are really friendly. I still struggle to go up and ask people, but I’ve generally always had really helpful advice or just a different way of viewing things from somebody that I wouldn’t have expected. But they just come out with a question and it kind of changes your whole perspective on something that you were stuck on.

Dr Mike Daniels:

Nice. Thank you. And then I guess we’ll go on to Soraya, who has completed her PhD and is now doing a postdoc, so might have even more, in fact is one of the postdocs that Tabitha loves so much. So, she might have even more information for us and tips and advice.

Dr Soraya Meftah:

I would completely agree with both Tabitha and Jack. If you ask someone quickly, well, if you ask someone when you have a problem, sometimes they’ve already had that problem and you get it solved quickly. But I was thinking of trying to give a bit of advice that was slightly off the normal. And so, what I would say is when you go to seminars, conferences, et cetera, is to ask a question even if it means absolutely nothing to you. I like to ask questions a lot, but it took me a long time to build up to the point where I felt confident doing so. So, it could be in a lab meeting or in a ridiculously small local seminar.

Dr Soraya Meftah:

If you ask one question, I guarantee at least five other people will be thinking that same question, because if it wasn’t clear to you, then the speaker didn’t make it clear enough. And it’s on them, it’s not on you, basically. And I tend to find that that keeps me more engaged and I’m thinking about my question, and then I ask it, and actually I tend to get some very interesting responses. So that would be my one tip.

Dr Mike Daniels:

I guess that’s such a confidence thing, isn’t it? I don’t know when, me being kind of four odd years post PhD, I’m probably still not at the level where I can just go straight in and say, “Well, you haven’t made it clear enough to me and so I want to ask that question, professor.”

Dr Soraya Meftah:

I wouldn’t start it like that.

Dr Mike Daniels:

I didn’t mean literally say that as kind of the reason I’m asking the question. That would be really bad. Okay, we’re kind of coming to the end of, I think what I was hoping to talk about. And I’ve ended up, I’ve just realized, going a little bit off the topic of neural activity. So, for a last point, I want everyone to come back to that. And I’ll ask you all again, I guess we can go around unless anyone is happy to jump in on this, for what the hot topic and the kind of real current, maybe the hot topic now, or maybe what people are working on right now, what the biggest question is, specifically in your kind of aspect of your field. So, for instance, Jack kind of doing the EEG research.

Dr Mike Daniels:

What the thing that most people are really keen to learn? What’s the hot topic, and what are people desperately trying to work out? What’s the most important thing they’re trying to find? And again, I’ll have to apologize because I’ve not prepared our panelists for this question, so they’re all going to have to come up with it off the top with their heads. So, if anyone wants to fly in on it, if not, we’re going to have to put Jack on the spot.

Jack Bray:

Yeah. I guess the biggest thing for EEG research at the minute is, we’ve kind of been at it for a while, but it’s kind of understanding how this buildup of toxic protein does actually affect the underlying neural activity. A big thing, obviously at the moment, there’s a lot of talk now about how the amyloid hypothesis, as it were, is kind of dying. There was a paper published recently, the death of the amyloid hypothesis. So, I guess maybe that’s kind of the biggest thing currently. It’s kind of like working out why the amyloid hypothesis has failed, and how maybe the tau pathology would be a better model.

Dr Mike Daniels:

Well done on such being put on the spot. Fortunately, Tabitha and Soraya have had a few extra seconds now to take some notes, thanks to Jack taking the hit for them. And Tabitha, what’s the kind of big hot topic for you just now?

Tabitha Broadbelt:

Well, I think that there’s two. I think that there’s some really interesting research being done of people trying to adapt memory studies that work for both mice and humans so you can compare those. And I think that’s going to be really, really interesting moving forward, looking at our models and Alzheimer’s patients in these tasks. And then I think kind of coming maybe back a bit more to the neural activity, still trying to understand what’s happening to these memories in the cells. Are they being lost or are they just losing the signal and the connections? And I think that’s going to be a really key question for the Alzheimer’s community.

Dr Mike Daniels:

Thank you. And then finally, the person with the most experience, and who we gave the most amount of time to come up with the answer to this question. So, this had better be good, Soraya.

Dr Soraya Meftah:

I was distracted by Jack saying about death to the amyloid hypothesis, when me and Tabitha are both working in amyloid models.

Jack Bray:

Sorry.

Dr Soraya Meftah:

So, I think actually my one kind of thing that I think is a hot topic, or what’s really a big question in the field, is this idea of kind of compensation from neuronal activity. So, within dementia, we know that there’s, well within neurodegenerative diseases, we see this massive neuronal loss. But actually, quite a lot of these changes occur before we see any changes in behavior. And so, there’s this idea that this kind of plasticity within networks or kind of homeostatic compensation, some kind of way that the neuronal signals are still being preserved, but we are losing connections, neurons, et cetera. And so, trying to understand what physiological changes are going on that allows people to carry on going as they have been whilst they have all these massive changes in the brain, I think would be super important to identify as something going forward for a biomarker treatment, et cetera.

Dr Mike Daniels:

That’s fantastic. And yeah, thank you very much, everyone. So, it’s now time to end today’s show. And I’d like to get my massive thanks to guests Jack, Soraya, and Tabitha. We’ve spoken today on neural activity in dementia research. We’ve heard from researchers working throughout the spectrum of neural activity from single cells through to kind of broad-spectrum EEG recordings, and then into the output of all that in terms of behavior. We’ve spoken about how mouse models may be used to investigate human disease. And we’ve spoken about how reproducibility in those mouse models is so important for dementia research and what we’re doing. And we’ve had some great tips from our expert dementia guest researchers. And we’ve also had a little bit on the spot very briefly at the end about the real hot topics in their specific fields and what they hope for in the future.

Dr Mike Daniels:

And so, if there aren’t any final points to make from any of our panelists, I’ll finish up. And we have profiles of all of today’s panelists on the website, including details of their Twitter accounts, if they have them, so please take a look. There you’ll find loads of other content, support blogs, listings, articles for dementia researchers, just like you and I personally can really, really vouch for this website. Includes also some really interesting details on funding, which is fantastically put together. And finally, please remember to like and subscribe in whichever app you are listening in. So, thank you very much for listening, and goodbye

Voice Over:

Brought to you by dementiaresearcher.nihr.ac.uk in association with Alzheimer’s Research UK and Alzheimer’s Society. Supporting early career dementia researchers across the world.

END


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