Sluglab 2019 – It will be an unforgettable summer

- rcalinjageman

It’s summer and the slug lab is rocking. We have 8 students working in the lab (!), and a number of really exciting projects.

Here’s the lab photo to start the summer.

From left to right: Kiara Rana, Dr. C-J, Dr.Bob, Tania Rosiles, George Garcia, Annette Garcia, Hannah Gordon, Lorena Juarez, Monica Duron, and Melissa Nguyen

We knew this spring that we had recruited a special group of students in to the lab. So far the work this summer has confirmed our hunch–we’ve already completed two rounds of behavioral testing, students are making progress learning qPCR, and yesterday we had a great start to learning electrophysiology. I’m sure we’ll have our ups and downs, but it seems like we’re poised for a fun and productive summer.

Projects we’ll be working on include: 1) investigating if savings memories are re-formed or re-covered, 2) investigating the role of the peptide transmitter FMRF-amide in forgetting, 3) exploring the role of methylation in memory maintenance, and 4) some exciting pilot testing with a paradigm for sensitization in fruit fly larva, in collaboration with Scott Kreher in biology.

Our work this summer continues to be supported by the NIH (our current R15 expired at the end of May, but looks like it will be renewed starting July 1). Huzzah.

In addition, Dominican has received a generous donation from Joe Moskal to start the Moskal scholars program. Joe is a professor of biomedical engineering at Northwestern, a biotech entrepreneur, a Dominican trustee, and an all-around amazing guy. He generously helped Irina and me develop pilot data for our first grant and provided a sparkling letter of support… so it is no exaggeration to say he has already helped make the slug lab what it is today.

This year, Joe took the next step in his efforts to develop and broaden the biotech pipeline by funding the Moskal scholars program. Over the next five years this program will fund students interested in careers in the life and health sciences to spend a summer engaged in intensive research. The goal is for students to have the space, mentoring, and encouragement to develop their skills and passions in the science, and to launch them forward to great things.

Our first two Moskal scholars are Annette Garcia and Tania Rosiles. Tania will be spending her second summer in the slug lab–she’s already gained tremendous lab skills and helped co-author our recent paper on the long-term transcriptional response to sensitization ​(Patel et al., 2018)​. Annette is new to the lab, but was a star in Dr. C-J’s neurobiology class and has already been making big strides in the lab.

The inaugural Moskal Scholars: Annette Garcia and Tania Rosiles

Neither Irina nor I would be where we are today if we hadn’t been fortunate enough to have amazing summer experiences. For Irina it was a summer working at Loyola Medical School. For me, it was a summer at Carnegie Mellon. In both cases it was generous funding from sponsors that enabled us to forgo our usual summer jobs and spend 3 months in intense and life-altering contemplation and study. We are so excited and proud to pay that forward each summer with a new batch of slug lab recruits, and we’re extremely grateful to Joe Moskal for his generosity and support.

One of our annual summer traditions is having DU photographer Ryan Pagelow come to the lab for a group photo and some science B-roll. As always, he does an amazing job. Here’s this year’s album:

 
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  1. Patel, U., Perez, L., Farrell, S., Steck, D., Jacob, A., Rosiles, T., … Calin-Jageman, I. E. (2018). Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica. Neurobiology of Learning and Memory, 474–485. doi: 10.1016/j.nlm.2018.09.007

Updated word search and mirror-tracing tasks for Qualtrics

- rcalinjageman

I finally had some spare time to document and post the mirror tracing and word-search tasks I developed for some replication work my students and I completed ​(Cusack, Vezenkova, Gottschalk, & Calin-Jageman, 2015)​.

Each task is (I think) pretty nifty, and I’ve had lots of emails about them over the past couple of years. I’ve finally posted both code bases to github along with working demos in Qualtrics and some rudimentary instructions. The code itself is not pretty–I was learning javascript and wrote most it during a conference I was attending in Amsterdam. Still, it works, and I’m sure it could come in handy.

The mirror-tracing task is just like it sounds–participants trace an image with their mouse or track pad but the mouse movements are mirrored, making it hard to stay in the line. You can vary task difficulty by changing line thickness. There is an expected weak negative correlation with age. The script can even posts the traced images back to your server, which is cool for making figures showing how groups differ with representative data.

The word-search task is also like it sounds. You can use pre-defined grids, or the script can generate a grid for you. I’ve used it to try priming for power (control vs. power-related words hidden in the grid) and to look at frustration (by having a grid that *doesn’t* have all the target letters…mean, I know).

  1. Cusack, M., Vezenkova, N., Gottschalk, C., & Calin-Jageman, R. J. (2015). Direct and Conceptual Replications of Burgmer & Englich (2012): Power May Have Little to No Effect on Motor Performance. PLOS ONE, e0140806. doi: 10.1371/journal.pone.0140806

Kids, Neurons, and Robots

- rcalinjageman

At the end of February I (Dr. Bob) visited a local elementary school as part of the Oak Park Educational Foundation’s Science Alliance Program.

I was matched up with Sue Tressalt’s Third Grade Class at Irving Elementary. For an activity, I brought along the neuroscience program’s collection of Finch Robots, a set of laptops, and the Cartoon Network simulator I have been developing (Calin-Jageman, 2017, 2018). I introduced kids to the basic rules of neural communication, and they explored Cartoon Network, learning how to make brains to get the Finch Robots to do what they wanted (e.g. avoid light, sing when touched, etc.). It was a great class, and a ton of fun.

I’m proud of Cartoon Network, and the fact that it can make exploring brain circuitry fun. It’s simple enough that the kids were able to dive right in (with some help), yet complex enough that really interesting behaviors and dynamics can be modelled.

As a kid, my most formative experience in science was learning logo, the programming language developed by Seymour Papert and colleagues at MIT. Logo was fun to use, and it made me need/want key programming concepts. I clearly remember sitting in the classroom writing a program to draw my name and being frustrated at having to re-write the commands to make a B at the end of my name when I had already typed them out for the B at the beginning of my name. The teacher came by and introduced me to functions, and I remember being so happy about the idea of a “to b” function, and I immediately grasped that I could write functions for every letter once and then be able to have the turtle type anything I wanted in no time at all.

Years later I read Mindstorms and it remains, to my mind, one of the most important books on pedagogy, teaching, and technology. Papert applied Piaget’s model of children as scientists (he had trained with Piaget). He believed that if you can make a microworld that is fun to explore, children will naturally need, discover, and understand deep concepts embedded in that world. That’s what I was experiencing back in 2nd grade–I desperately needed functions, and so the idea of them stuck with me in a way that they never would in an artificial “hello world” type of programming exercise. Having been a “logo kid” it was amazing to read Mindstorms and recognize Papert’s intentionality behind the experiences I had learning Logo.

Anyways, bringing Cartoon Network to an elementary school for a day gave me a great feeling of carrying on a tiny piece of Papert’s legacy. The insights kids develop in just an hour of playing with neural networks are amazing–the idea of a recurrent loop made immediate sense to them, and that also sets up the idea that both excitation and inhibition are important. And, like in Logo, the kids were excited to explore–to know that their experience was not dependent on getting the ‘right’ answer but on trying, observing, and trying again.

The day was fun and even better I received a whole stack of thank-you cards this week. Reading through them has kept a smile on my face all week. Here’s a sample.

This kid has some great ideas for the future of AI

“I never knew neurons were a thing at all”–the joy of discovery
“Your job seems awesome and you are the best at it”—please put this kid on my next grant review panel.
  1. Calin-Jageman, R. (2017). Cartoon Network: A tool for open-ended exploration of neural circuits. Journal of Undergraduate Neuroscience Education : JUNE : A Publication of FUN, Faculty for Undergraduate Neuroscience, 16(1), A41–A45. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/29371840
  2. Calin-Jageman, R. (2018). Cartoon Network Update: New Features for Exploring of Neural Circuits. Journal of Undergraduate Neuroscience Education : JUNE : A Publication of FUN, Faculty for Undergraduate Neuroscience, 16(3), A195–A196. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/30254530

SlugLab Alum Derek Stek heading to medical school with a full ride scholarship

- rcalinjageman

Graduates of the sluglab have been moving on to amazing careers. So we were excited to get the news that lab alumni and neuroscience major Derek Stek has just been offered a full scholarship to attend medical school at the School of Medicine and Public Health at the University of Wisconsin. Woo hoo!

The slug lab in summer of 2018. Derek is the tall guy on the left-side of the table; this was just before he shipped out to UCLA.

Derek spent the summer of 2017 working in the lab, and also did summer research programs at the University of Colorado (2016) and UCLA (2018). In the sluglab, Derek learned how to do extract RNA (which does *not* start by vortexing the DNA-ase) and conduct qPCR. He helped track the expression of several transcripts regulated after learning, and was a co-author on the lab’s most recent paper (Patel et al., 2018).

Derek was also a star outside of the classroom, playing a big part on the DU varsity basketball team. This year, as he finishes at DU, Derek has been working with children with autism and learning behavioral therapy.

Congrats, Derek!

  1. Patel, U., Perez, L., Farrell, S., Steck, D., Jacob, A., Rosiles, T., … Calin-Jageman, I. E. (2018). Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica. Neurobiology of Learning and Memory, 474–485. doi:10.1016/j.nlm.2018.09.007

The remarkably long-lasting fragments of memory

- rcalinjageman

It was a whirlwind 2018. Irina and I are just now catching our breath and finding some time to update the lab website.

One awesome piece of news we forgot to publicize is that our latest paper came out in the August issue of Neurobiology of Learning and Memory (Patel et al., 2018).   This paper continues our work of tracking the molecular fragments of a memory as it is forgotten.  Specifically, we tracked 11 genes we suspected of being regulated *after* forgetting (Perez, Patel, Rivota, Calin-Jageman, & Calin-Jageman, 2017).  Things didn’t work out quite as well as we had expected: of our 11 candidate genes 4 didn’t show much regulation, meaning that our previous results with these genes were probably over-estimating their importance (curse you, sampling error!).  On the other hand, we replicated the results with the other genes and found that some of them are actually regulated for up to 2 weeks after the memory is induced, long after it seems forgotten.

Here are two key figures.  The first is the memory curve for sensitization in our Aplysia -it shows that after memory induction there is strong sensitization recall that decays within a week back to baseline.  Even though the memory seems gone, giving a reminder 2 weeks after learning rekindles a weak re-expression of the memory. That’s a classic “savings” effect.  

The next figure traces the time-course of memory-induced gene expression (levels of mRNA) for 6 specific genes, measured in the pleural ganglia that contains neurons known to be important for storing sensitization memory.  You can see that each of these transcripts is up- or down-regulated within 24 hours of learning, and that in each case this regulation lasts at least a week and sometimes out to 2 weeks.  So, just as the behavioral level of the memory fades but isn’t really completely gone, the some of the transcriptional events that accompany learning also seem to persist for quite some time. 

Why would this occur?  Perhaps these transcripts are part of savings…maybe they set the stage for re-expressing the memory?  Or maybe they are actually part of forgetting, working to remove the memory?  Or maybe both?  For example, one of the transcripts is encodes an inhibitory transmitter named FMRFamide.  It is really up-regulated by learning, which would normally work against the expression of sensitization memory.  So perhaps this helps suppress the memory (forgetting), but in a way that can be easily overcome with sufficient excitation (savings)… that’s an exciting maybe, and it’s the thing we’ll be working this summer to test.

As usual, we’re so proud that this paper was made possible through exceptional hard work from some outstanding DU student researchers: Ushma Patel, Leticia Perez, Steven Farrell, Derek Steck, Athira Jacob, Tania Rosiles, and Melissa Nguyen.  Go slug squad!

Patel, U., Perez, L., Farrell, S., Steck, D., Jacob, A., Rosiles, T., … Calin-Jageman, I. E. (2018). Transcriptional changes before and after forgetting of a long-term sensitization memory in Aplysia californica. Neurobiology of Learning and Memory, 155, 474–485. doi:10.1016/j.nlm.2018.09.007
Perez, L., Patel, U., Rivota, M., Calin-Jageman, I. E., & Calin-Jageman, R. J. (2017). Savings memory is accompanied by transcriptional changes that persist beyond the decay of recall. Learning & Memory, 25(1), 45–48. doi:10.1101/lm.046250.117

New preprint on the very long-lasting transcriptional response to learning

- rcalinjageman

The sluglab has a new preprint out, currently under review at the Neurobiology of Learning and Memory.  We shows that both transcription and savings can persist for as long as 2 weeks after the induction of long-term sensitization, way beyond the decay of recall.  Interestingly, all the long-lasting transcriptional changes start within 1 day of training.  Lots of student co-authors on this one; it was a *lot* of work.  Looking forward to the reviews.

When you forget

- rcalinjageman

Quanta Magazine recently ran a feature article on the nature of forgetting.  The piece covers several new lines of research on forgetting, including the work we’ve been doing with Aplysia.  It’s a great piece, and it’s amazing to see strong public interest in our work.

To Remember, the Brain Must Actively Forget by Dalmeet Singh, Quanta Magazine

Of course, accolades like this would not be possible if it were not for our amazing students.  Here’s the lab enjoying our end-of-summer party.

 

DU Connections and a New Slug Home

- rcalinjageman

The slug lab is kicking off summer research with a brand new aquarium and mixing station for housing Aplysia.  It’s a great upgrade and an even better story that involves some strong DU connections.

The slug lab has been running for 10 years now (gasp!) and our aquariums were showing signs of wear.  Like the wooden stand on one of the tanks starting to collapse.  Pretty strong sign.  (fortunately a student was in the room as the tank started to tip; she called for help, we drained the tank, and disaster was averted).  By fall of 2017 we were down to just 1 tank and worried about how we’d get back to 2 in time for our blitz of summer research.

DU Connection Number 1: In late fall 2017 we were thrilled to receive a McNichols grant from a Dominican Alumni.  This grant was specifically targeted at funding science education at Dominican. We had some meetings and identified several great projects that could be helped by this generous gift–work to improve our greenhouse, a new measurement instrument for the PChem lab, and… a new tank for the slug lab.  Hooray, and a big thanks to the McNichols family.

DU Connection Number 2: We knew we wanted to upgrade beyond a hobbyist tank.. but there were so many options and it was difficult to determine the best path forward.   Enter DU connection #2, Romney Cirillo and his company Something Fishy.  Romney was a business major at Dominican.  When he graduated he wasn’t entirely sure what to do.  But he remembered Al Rosenbloom’s advice to find something he was passionate about and to find a way to make it a life’s work.  Combining that advice with a great entrepreneurship class he had completed, Romney decided to start a business related to his life-long interest in raising exotic fish.  He recruited a great friend as a business partner.  Something Fishy was quickly born as a full-service aquarium design and maintenance company.   Since its founding, Something Fishy has thrived by providing great service and incredible craftsmanship.  Things were going well, so Romney started giving back to DU–installing a gorgeous salt-water tank in Parmer hall.  That’s how I met Romney and got to know Something Fishy.  So, naturally, when it came time for a new tank, Romney was the first person to call.  Thank goodness for these strong DU connections.

The amazing tank.  Romney and Mike visited the slug lab, walked us through options and designed a customized setup exactly suited for our needs:

  • a bigger tank with a better filter system
  • lower to the ground with a huge lid to make experimental access easier (our students say thank you!)
  • incredibly tough and corrosion resistant tank stand (no more collapses from wooden stands)
  • better insulation to make our chillers work less hard
  • and an incredible mixing station for making salt water, complete with a DI line and an auto-shutoff (no more leaks down into the classroom below).

We just finished our first round of experiments with animals housed in the new tank… wow!  Even on the day of shipment the tank water stayed at crystal clear.  Good water -> healthy animals -> a good platform for good science.

Not only is the tank *way* better than what we had, it looks amazing–the install is clean and sharp; it really looks space age.  Best of all, the cost was not astronomical.

So – thanks to two great DU alum we have a great new home for our animals.

Romney (right) showing me the features of the tank on install day.

Here are some photos, but they don’t really do the tank justice for how cool and clean it all looks.

First fillup. Water has just had salt added.

Smiles even on tank cleaning day! The new tank setup is soooo sharp. (Melissa, Ushma, and Leticia… there are slugs in the tank, but all are hiding in the back).