 Hi everyone, my name is Emma Lefth, I'm a postdoctoral researcher at Obus University in the Department of Biomedicine, and I'm here today to talk to you about my research. In our laboratory, we are working on basic neuroscience research directly with human brain tissue samples. Researchers in biomedicine are constantly working to improve current treatments for disease and find new drug targets. However, most of this preclinical research is conducted in petri dishes or in rodent models. Is this the most effective way to test for new drug targets? Only a very small percentage of drugs from preclinical studies actually make it all the way through human clinical trials to get approved. In neuroscience, this can be a really large issue. I mean, is the rodent brain, the size of a peanut, a good model for the human brain? Let's talk about some of the similarities and differences between the mouse and human brain. Both brains have the same basic structures. We look at the cortex, this area here. We can see some differences. The cortex is known as a place for higher order thinking. It allows us to be logical and is one of the main things that sets us apart from other mammals. In the human brain, we have all these convolutions so that we can fit even more cortex in our heads. Whereas in the mouse, that area is flat. So human brains have a lot more cortex. But what if we look inside? Are they organized differently as well? If we look here at a sample of a piece of cortex and we stain for all the neurons, so all the principal cells of the brain, we can see that in both the mouse and human, they're organized into layers. So in the mouse, you can see this sparsely populated layer 1 and then a more dense band around layer 2. And then some slight differences throughout the other layers go deeper in towards the middle of the brain. In the human, we also have layers. We still have this sparsely populated layer 1, kind of a more dense layer 2. However, as you can see, there's a lot more cortex. And so we can actually subdivide some of these layers into layer 4a, b, and c, for example. And you can see here that in layer 4b, there's not so many of these cells, whereas we don't see the same effect in the mouse. But then we can go a step further and genetically characterize these neurons. So if we look at the genetic characterization, what we find is actually that a lot of cells are expressed similarly and in similar layers in the mouse and human. And that's also what we see here on this graph. All these black dots are cells that are expressed in both human and mouse brains. However, you can see that there's a large chunk of cells that are solely expressed in the mouse brain, and also a large chunk that are solely expressed in the human brain. So I mean, this has been a really basic and very brief overview. But the point is to illustrate that while there are definitely some conserved structures and the same basic organization, there are still some definite differences and different neuron types that are expressed between these two types of brains. And this can have a huge effect on drugs that are targeting specific types of neurons. So we are fortunate here at Olwes University to have a collaboration with the neurosurgery team at Olwes University Hospital, where we receive living brain tissue samples from generous donors. These donors are patients that are already undergoing a surgery to have a piece of their brain removed. So we receive a piece of cortex that would normally have just been thrown away. So first step of this process is I go to Olwes University Hospital, and I wait outside the operating room hallway, where a nurse will bring me that piece of tissue very quickly after it's been removed from the patient. So here I am just removing any excess blood and making sure that the tissue is the correct size for transport. And throughout this process, we keep that little tissue sample in artificial cerebral spinal fluid. So this is a fluid made up of ions that's meant to mimic the cerebral spinal fluid that your brain is floating in in your head anyway. And this is to keep all those neurons alive and healthy so that we can work with them throughout the day. Step two, we bring that sample to the laboratory. I'm usually a bit too busy focusing on the sample and what I'm doing to take my own pictures, but here's an example from a paper from a group in Germany who works in a similar way. And so this is an example of what the human brain tissue sample actually looks like. From there, we slice the brain very thin and store them in a specialized container similar to this one. Again, still submerged in artificial cerebral spinal fluid to keep these slices alive throughout the day. And so from here, you can do a number of different techniques in order to study these samples. However, in our lab, we use one called electrophysiology. So this is recording the electrical signal from individual neurons. So this is an example of some of those electrical signals. What we do is we take one of those thin brain slices and we put it under a microscope, such as the one seen here from our laboratory. And their artificial cerebral spinal fluid is flowing over it the entire time. And then I am able to go in with a recording electrode as seen here and actually record from individual neurons. So what I see on the screen is something that looks like this. And all these triangular shapes are actually neurons. And so I can go and record this electrical signal from those. And from there, I can apply different drugs and see, you know, how that might change the electrical signal. So the overall goal of this work is to create a better platform for drug testing, for treatments that directly affect the brain. We aim to receive these human brain samples directly from the hospital, complete our electrophysiological recordings like I described on the last slide, and then test different drugs while doing this. And from there, we hope to be able to make better recommendations on what drugs should move to the next stage of preclinical testing. For our current research, we are studying the effect of dopamine on human cortical neurons. So dopamine is a neurotransmitter that your brain already produces and is typically associated with reward and addiction. So it's been talked about a lot in the news of the addiction of social media, how likes increased opening in the brain. But we're looking at though is our hypothesis is that dopamine can strengthen neuron connections and therefore may be a possible drug target to improve recovery following brain injury. This is in order to help neurons rewire and strengthen their connections during the healing process. So this work will hopefully provide better translational research to improve the drug development process. And for this work, it involves a lot of people, in particular, the leader of our laboratory, Dr. Marco Caponia, the neurosurgery team at Opus University Hospital, our collaborators, and of course, our funding partners. Thank you so much for listening, guys.