The slug lab has a new paper out, again with student co-authors (Tania Rosiles and Melissa Nguyen, congrats!):

Rosiles, Tania, Melissa Nguyen, Robert J. Calin-Jageman, and Irina E. Calin-Jageman. “Transcriptional Changes Fade Prior to Long-Term Memory for Sensitization of the Aplysia Siphon-Withdrawal Reflex.” Eneuro, March 9, 2026, ENEURO.0477-25.2026. https://doi.org/10.1523/ENEURO.0477-25.2026.

It was a long road for this project… we started it in 2016! But with Covid and lots of other disruptions it took a long while to all the way to publication. Time for some well-aged champagne.

The wait has been worth it in part because this project is really interesting. We have previously shown that forming a new long-term sensitization produces remarkable changes in gene expression within 1 day of training, with clear up- and down-regulation of almost 1200 distinct transcripts (that’s nearly 5% of all the gene models in the Aplysia genome). In this project, we tracked these genes to 5 days after training, a time point where the memory is partly, but not fully forgotten. To our surprise, we found that only 4 of the transcripts regulated 1 day after training were still regulated 5 days after training: 99% were no longer significantly regulated. This wasn’t due to low power: we used N = 16 paired samples and we were even able to show that 99% of transcripts showed a statistically-significant decline in regulation from day 1 to day 5. This wasn’t just about forgetting — we found the same result even when isolating to the 8 samples from animals that had shown the least forgetting. No, our results show that some aspect of the initial transcriptional response to learning is greatly modified/attenuated over time, even while the memory remains expressed! This could mean the locus of storage changes (gene expression changes continue, but in different neurons than at first), that it is refined (only a few neurons sustain the gene expression changes), or perhaps that it is offset (whatever changes that occur in memory-storing neurons are then offset by non-storing neurons to keep overall transcription as it was before)… all exciting possibilities to explore!

This paper marks the 12th paper from the SlugLab.. a nice dozen of papers since our first successful project in 2012. That’s pretty incredible for our student-powered lab! For anyone wanting the boxed set, here’s our current complete bibliography:

Bonnick, Kristine, Karla Bayas, Dmitry Belchenko, et al. “Transcriptional Changes Following Long-Term Sensitization Training and In Vivo Serotonin Exposure in Aplysia Californica.” PLoS ONE 7, no. 10 (2012): e47378. https://doi.org/10.1371/journal.pone.0047378.

Calin-Jageman, Robert J., Bryan Gonzalez Delgadillo, Elise Gamino, et al. “Evidence of Active-Forgetting Mechanisms? Blocking Arachidonic Acid Release May Slow Forgetting of Sensitization in Aplysia.” Research Article: New Research. eNeuro 11, no. 4 (2024). https://doi.org/10.1523/ENEURO.0516-23.2024.

Calin-Jageman, Robert J., Theresa Wilsterman, and Irina E. Calin-Jageman. “Transcriptional Regulation Underlying Long-Term Sensitization in Aplysia.” In Oxford Research Encyclopedia of Neuroscience. 2024. https://doi.org/10.1093/acrefore/9780190264086.013.499.

Conte, Catherine, Samantha Herdegen, Saman Kamal, et al. “Transcriptional Correlates of Memory Maintenance Following Long-Term Sensitization of Aplysia Californica.” Learning & Memory 24, no. 10 (2017): 502–15. https://doi.org/10.1101/lm.045450.117.

Cyriac, Ashly, Geraldine Holmes, Jamie Lass, Dmitry Belchenko, Robert J. Calin-Jageman, and Irina E. Calin-Jageman. “An Aplysia Egr Homolog Is Rapidly and Persistently Regulated by Long-Term Sensitization Training.” Neurobiology of Learning and Memory 102 (May 2013): 43–51. https://doi.org/10.1016/j.nlm.2013.03.008.

Herdegen, Samantha, Catherine Conte, Saman Kamal, Robert J. Calin-Jageman, and Irina E. Calin-Jageman. “Immediate and Persistent Transcriptional Correlates of Long-Term Sensitization Training at Different Cns Loci in Aplysia Californica.” PLoS ONE 9, no. 12 (2014): e114481. https://doi.org/10.1371/journal.pone.0114481.

Herdegen, Samantha, Geraldine Holmes, Ashly Cyriac, Irina E. Calin-Jageman, and Robert J. Calin-Jageman. “Characterization of the Rapid Transcriptional Response to Long-Term Sensitization Training in Aplysia Californica.” Neurobiology of Learning and Memory 116 (December 2014): 27–35. https://doi.org/10.1016/j.nlm.2014.07.009.

Holmes, Geraldine, Samantha Herdegen, Jonathan Schuon, et al. “Transcriptional Analysis of a Whole-Body Form of Long-Term Habituation in Aplysia Californica.” Learning & Memory 22, no. 1 (2014): 11–23. https://doi.org/10.1101/lm.036970.114.

Patel, Ushma, Leticia Perez, Steven Farrell, et al. “Transcriptional Changes before and after Forgetting of a Long-Term Sensitization Memory in Aplysia Californica.” Neurobiology of Learning and Memory 155 (November 2018): 474–85. https://doi.org/10.1016/j.nlm.2018.09.007.

Perez, Leticia, Ushma Patel, Marissa Rivota, Irina E. Calin-Jageman, and Robert J. Calin-Jageman. “Savings Memory Is Accompanied by Transcriptional Changes That Persist beyond the Decay of Recall.” Learning & Memory 25, no. 1 (2018): 45–48. https://doi.org/10.1101/lm.046250.117.

Rosiles, Tania, Melissa Nguyen, Robert J. Calin-Jageman, and Irina E. Calin-Jageman. “Transcriptional Changes Fade Prior to Long-Term Memory for Sensitization of the Aplysia Siphon-Withdrawal Reflex.” Eneuro, March 9, 2026, ENEURO.0477-25.2026. https://doi.org/10.1523/ENEURO.0477-25.2026.

Rosiles, Tania, Melissa Nguyen, Monica Duron, et al. “Registered Report: Transcriptional Analysis of Savings Memory Suggests Forgetting Is Due to Retrieval Failure.” Eneuro 7, no. 6 (2020): ENEURO.0313-19.2020. https://doi.org/10.1523/ENEURO.0313-19.2020.

Doing science isn’t always cheap. The sluglab has been very fortunate to have had multiple rounds of funding from the National Institute of Health to support our research. Specifically, we’ve been supported by R15 grants, a grant program designed specifically for undergraduate-focused labs. These grants are much smaller than the R01s obtained at larger universities (an R01 can be for up to $1 million/year for 5 years; an R15 is a total of $300,000 over 3 years), but they provide an opportunity to fund research with undergraduate researchers (one big complaint about this program, though, is the short timeline — R15s are on a much shorter cycle even though it typically takes *more* time to finish projects in an undergrad-focused lab).

The sluglab has had the good fortune to have strong R15 funding from the NIH. We got started in 2009 with an R15 to study long-term habituation. That project went well ​(Holmes et al., 2014)​, but also showed us that we could get more accomplished studying long-term sensitization. So in 2014 we applied for and received funding to study the formation and forgetting of sensitization memory. This project went so well that we renewed it in 2018.

This year (2024), in February, we applied to renew the project again. Putting together a grant application is *tough* — you have to review your progress from the previous grant and then make a good case that you have additional important, clear research questions along with the ability to answer those questions. Fortunately, our last round of funding was really productive — we mapped the transcriptional bases of savings memory ​(Rosiles et al., 2020)​, found experimental validation for our dual-process model of forgetting ​(Calin-Jageman, Gonzalez Delgadillo, et al., 2024; Perez, Patel, Rivota, Calin-Jageman, & Calin-Jageman, 2017)​, and wrote a new synthesis on the transcriptional mechanisms of sensitization ​(Calin-Jageman, Wilsterman, & Calin-Jageman, 2024)​. We also worked hard to develop some really strong new research projects, proposing to compare forgettable and unforgettable forms of sensitization memory with single-cell resolution and to test our theory of forgetting at the cellular level. With a ton of coffee and work, we developed our renewal application and sent it in.

And then we waited. Submission in February gets your grant reviewed in mid-June. You get your scores within a few days, then written comments within a few weeks, then there is a council meeting several months later at which actual funding decisions are made. It is quite a process.

It’s now July, so we still have a ways to go before council and the official decision… but we are excited to share that our grant was very highly scored — in the top 4% of grants reviewed this cycle. That’s not a guarantee, but we can still feel pretty good about ultimately being funded. So: huzzah — the sluglab will have the funding needed to continue training both sea slugs and undergrads, at least for the next several years to come. Can’t wait to see all we can accomplish on this next grant.