The remarkably long-lasting fragments of memory

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

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

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

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).

Slug Lab 2018 – Summer Edition

Summer is here, so the Slug Lab is running full speed.

We’re lucky to be joined once again by a really talented and dedicated team of students.  Here’s most of us at a pizza party to inaugurate a summer of research.  

From far left we have

  • Kayla Hall, joining us from Amherst for the summer
  • Ushma Patel, who has graduated but will stay in the lab for the start of the summer (and then on to study biomedical illustration at UIC)
  • Athira Jacob, lab alum now studying for her MCAT
  • Derek Steck, lab alum who this summer will be in the UCLA summer research program this summer
  • Steven Farrell, who has graduated but is also sticking with the lab for part of the summer while prepping for the MCAT
  • Dr C-J and myself (end of the table)
  • Tanya Rosiles, new lab member
  • Everett Krause, new lab member
  • Leticia Perez, lab alum sticking around for part of the summer before heading to UofI for veterinary medicine
  • Melissa Nguyen, new lab member and post-bac student

And not yet in the photo but planning on joining when she returns from Ireland: Shannon Wilcox

I hope I don’t jinx anything when I say that we’re off to a great start, with a very successful round of behavioral experiments and RNA isolations.  Looking forward to another great slug lab summer.

 

Slug Lab Triumph! First place in the cSFN undergraduate poster competition for Leticia Perez and Ushma Patel

So pleased and proud to announce that Leticia Perez and Ushma Patel have won first place in the Chicago Society for Neuroscience undergraduate poster competition.   Congrats Leticia and Ushma on a great presentation on the work you’ve been doing in the slug lab on the transcriptional correlates of forgetting and savings memory.

Leticia and Ushma are following up their spectacular win with exciting post-graduation plans.  Leticia is enrolling at the University of Illinois School of Vetrinary Medicine (and had her choice of programs!).  Ushma is enrolling at UIC’s prestigious medical illustration MA program (and also had her choice of programs!).  Congrats to both on all the hard work they put into collecting data, analyzing results, and presenting their exciting research.

Want to know more about the research Leticia and Ushma presented?  See their paper in Learning and Memory here: (Perez, Patel, Rivota, Calin-Jageman, & Calin-Jageman, 2017)

Not to brag, but this is the 3rd time a DU student has placed in this competition in the past 10 years (Kristine Bonnic had a 3rd place win and Tim Lazicki had a first place win).  That means DU neuroscience students have earned 1/3 of all the awards given out for undergraduate research by the Chicago Society for Neuroscience–an organization that includes Northwestern, Loyola, University of Chicago, DePaul, Midwestern, Roosevelt, North Central, and more…. relative to our student body we’re punching way above our weight!

Perez, L., Patel, U., Rivota, M., Calin-Jageman, I., & Calin-Jageman, R. (2017). Savings memory is accompanied by transcriptional changes that persist beyond the decay of recall. Learning & Memory (Cold Spring Harbor, N.Y.), 25(1), 45–48. [PubMed]

Memories fade..but something remains

Most long-term memories are ‘forgotten’–meaning that it becomes harder and harder to recall the memory.  Psychologists have long known, though, that forgetting is complex, and that fragments of a memory can remain.  For example, even after a memory seems forgotten it can be easier to re-learn the same material, something called ‘savings memory’.  That suggests that there is at least some fragment of a memory that persists in the brain even after it seems forgotten…but what?

Today our lab has published a paper shedding a bit of light on this long-standing mystery (Perez, Patel, Rivota, Calin-Jageman, & Calin-Jageman, 2017).  We tracked a sensitization memory in our beloved sea slugs.  As expected, memories faded–within a week animals had no recall of the prior sensitization.  Even more exciting, we found similar fragments of memory at the molecular level–there was a small set of genes very strongly regulated by the original training even though recall had fully decayed.

Why?  Do these persistent transcriptional changes help keep a remnant of the memory going?  Or are they actually doing the work of fully erasing the memory?  Or do they serve some other function entirely (or no function at all)?  These are some of the exciting questions we now get to investigate.  But for now, we have these fascinating foothold into exploring what, exactly, forgetting is all about in the brain.

As usual, we are enormously proud of the undergraduate students who helped make this research possible: Leticia Perez, Ushma Patel, and Marissa Rivota. Ushma, who wants to do science illustration, is making an incredible piece of artwork representing these findings.  A draft is shown above.  She submitted it for the cover of the journal, but sadly they journal selected a different image (boo!).  Still, a very exciting and proud day for the slug lab!

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.046250117

An unforgettable experience talking about forgetting

Wow! Our lab just returned from the 2017 Society for Neuroscience meeting.  It was the typical maelstrom of neuroscience–with more than 20,000 neuroscientists bustling about trying to share the latest and greatest about their research.

This turned out to be an especially great year for the Slug Lab.  Leticia Perez, who has been working in our lab for the past two summers, submitted an abstract to present the work she and others in the lab have been doing on forgetting.  We’ve been really excited about the results of this project.  It turns out the SFN organizers were excited, too–they selected Leticia’s abstract for a 10 minute talk during a mini-symposium on the mechanisms of learning and memory.

Leticia absolutely crushed it–she gave a concise, clear, and exciting presentation on what happens in the Aplysia nervous system as a long-term memory is forgotten.  She handled the questions wonderfully, and was soundly congratulated by many researchers in the learning and memory community.  Of the 20,000+ in attendance, I’m willing to be she was the only undergraduate to give a talk at this year’s meeting.  It was *such* an accomplishment.

In case that wasn’t enough, Leticia also brought along a poster presenting the research.  She gave the poster at the pre-meeting on molecular and cellular neuroscience and at the undergraduate poster session.  Yes, that means she gave 3 presentations last weekend!  Wow!  And, again, all went wonderfully.

Part of the reason Leticia was able to attend the meeting to earn all this acclaim is that she was awarded an Excel scholarship through Dominican University–this paid her registration, hotel, and airfare to make it affordable to attend the meeting.  She still had to work like crazy to collect the data, refine the presentation, and clear her class schedule to attend.  Lab alumnnus Marissa Rivota also attended–so her and Leticia also got to see the capital and the White house.

We’re so proud of Leticia, and of the many other students who have worked so hard in the lab for the past summers to make this forgetting project such a success.  There will be a paper on it coming out very soon in Learning and Memory.  It’s tremendous work to do good science–we’re so happy to have wonderful students who want to get involved and excel.

Below are photos of Leticia giving her talk, giving her poster, and celebrating with me, Irina, and Marissa.  Congrats, Leticia!