August 2019: Anacker Lab
Background:
What is the main focus of your lab?
The main focus of my lab is on how neural stem cells in the brain contribute to cognition and mood-related behaviors. A unique form of neuroplasticity is the ability of the adult brain to generate new neurons through the process of neurogenesis. In rodents and humans, this process takes place in the hippocampus, which is a brain region that has been implicated in learning and memory, as well as in emotional behavior and psychiatric disorders. New neurons that develop from stem cells in the dentate gyrus subregion of the hippocampus develop into mature cells that functionally integrate into the local neural circuitry. Our lab focuses on the question of how these new neurons control brain function and behavior by regulating neural circuits involved in emotions and congition. We have previously found that new young neurons can inhibit old cells in the dentate gyrus region of the hippocampus, and that this functional property of young neurons is involved in reducing anxiety and psychological stress responses in mice. Our goal is now to find new strategies to harness the potential of neural stem cells and new hippocampal neurons to treat, or prevent, psychiatric disorders as well as cognitive impairments.
How long have you had your lab? When did you join Columbia University?
My lab is brand new: We actually just started in January 2019. However, I myself have been at Columbia for a bit over 5 years already, because I did my postdoctoral work in René Hen’s lab from 2014 until 2019.
How big is your lab currently?
We currently have one postdoctoral fellow (Maryam Hasantash), two graduate students (Rushell Dixon, Neurobiology & Behavior Program; and Aaron Limoges, Biological Sciences Program), one research technician (Ryan Shores), one undergraduate student (Serena Wu), and a Fulbright graduate student from Portugal (Eduardo Campos), who will be joining our lab in October.
Where is your lab located?
We are in the Department of Psychiatry on the 6th floor of the Kolb building at 40 Haven Avenue.
Current affairs:
What are the most exciting projects/directions in the lab at this moment?
One of the most exciting projects in the lab is to use state-of-the-art in vivo Ca2+ imaging techniques in freely behaving mice to image the “online” activity of adult-born neurons in the brain during behavioral tests of learning & memory, and during stress-induced anxiety-like behavior. This is possible because we generated a new mouse line with which we can express an activity-dependent Ca2+ sensor specifically in neural stem cells and in the young neurons that develop from these stem cells. We then use head-mounted miniature microscopes that can be implanted into the brain of live mice to directly visualize the cellular activity of newborn neurons. This is an important tool for us to be able to address the question of how young neurons encode and store information about the environment, how young neurons are involved in learning & memory, and how their functional activity changes as a result of chronic psychological stress or during the course of aging. This allows us to gain unprecedented insight into the role of these cells for brain function and behavior that could not be addressed with previously available techniques.
What are the biggest accomplishments that your lab recently had?
OConsidering that we just started a few months ago, I think our biggest accomplishment is to bring together a fantastic team of highly motivated researchers who are passionate about using novel techniques to address the functional role of adult-born neurons for brain activity and behavior.
Technology:
What are the model systems that your lab is using?
We have a variety of transgenic mouse models in the lab with which we can regulate the number and the function of neural stem cells and adult born neurons in the brain. For example, we use a mouse line in which we can increase the number of adult-born neurons at any stage during development using a tamoxifen-inducible Cre-LoxP system to delete the pro-apoptotic gene, Bax, from neural stem cells (iBax mice). We also have a transgenic mouse line in which we can chronically silence the activity of adult-born neurons using inhibitory hM4Di DREADD receptors (NesCreERT2;hM4DiSTOP-floxed mice). Using these mice, we can investigate how changes in the firing activity of adult-born neurons contribute to brain function and behavior without changing the overall numbers of these cells. We also have a mouse line in which we can express the Ca2+ sensor, GCamp6f, specifically in neural stem cells and in the young neurons that develop from them (NesCreERT2;Ai95STOP-floxed mice). We can use these mice for in vivo Ca2+ imaging experiments in freely moving mice to measure when and how these cells are activated during learning, memory, and anxiety-related behavior. Finally, we have a mouse line in which we can express the serotonin 1A receptor (5HT1AR) specifically in the dentate gyrus to regulate neurogenesis and hippocampus activity. We are happy to share all these mouse lines with other labs.
What are the key techniques that your lab is using? Are you open to training scientists from other labs?
The key techniques we are using the lab are in vivo Ca2+ imaging with headmounted miniature microscopes in freely moving mice, optogenetic and chemogenetic techniques to manipulate the activity of specific cell types in the brain, viral- and dye tracing techniques to identify novel connections between specific cell types in different brain regions, viral-mediated knockdown or overexpression of genes, drug infusions into the brain using intracerebral cannulas, and x-ray irradiation to deplete the brain of neural stem cells. We use stereotactic surgery for all injections and implantations, and we use a variety of behavioral models to induce stress in mice either during adulthood (e.g., social defeat stress) or during early life (e.g., limited bedding model of early life stress). In addition, we use immunohistochemistry to quantify differences in the number of neural stem cells and adult-born neurons, and RNA sequencing in brain tissue samples to investigate gene expression changes in the brain following chronic stress and learning. We are very happy to train interested scientists from other labs in any of these techniques.
What facilities or equipment does your absolutely lab rely upon? Do you use CSCI cores?
We absolutely rely on stereotactic surgery equipment, miniature microscopes for in vivo Ca2+ imaging, and rodent behavioral testing facilities, which we all have available in our lab.
Training:
What's your best approach to mentoring trainees in the lab?
I think that every trainee comes to the lab with specific expertise and specific needs. I would say that understanding and addressing those individual requirements is important to provide appropriate, individualized mentoring.
What would be your career advice for students/postdocs?
Be creative, don’t be afraid of failure, ask for advice whenever you need it, enjoy the research you are doing, and always think of the bigger picture.
Lab management:
What was the most exciting part about starting your new lab?
The most exciting part is definitely assembling a team of people who are excited about the research and who work well together.
Which stem cell conferences does your lab attend?
New York Stem Cell Foundation
CSCI:
What was the main reason of you joining CSCI?
I think that one of the most important aspects of research is the ability to collaborate and to interact with scientists who are interested in similar scientific questions but who address these questions from a variety of different viewpoints and with a variety of complementary techniques. CSCI facilitates exactly that aspect of research by integrating different expertise in the stem cell field across various departments and research domains. There is a lot we can learn from each other by expanding our knowledge about how stem cell functions are regulated in different tissues, and by applying new technology to our individual research questions. I think that this integration of expertise has the potential to lead to true innovation in the stem cell field by opening up new avenues for collaboration and cross-disciplinary research.
What do you plan to bring to the CSCI community?
I’m hoping our lab will be able to contribute expertise and technology to investigate the functional role of neural stem cells to brain function and behavior.