Research

Aplysia Californica: Little Sea Slug - Big Breakthroughs in Learning and Memory

Jacob Umans, Meenu Johnkutty


Introduction

    Aplysia Californica, a sea slug, has played a major role in the advancement of neuroscientific knowledge over the past several decades. Due to its unique biological properties,  this model organism has been incredibly valuable to researchers investigating the molecular basis of learning and memory.

    Though small and unassuming at first sight, Aplysia Californica is a giant in the scientific world. Our first insights into long-term potentiation came from this seemingly insignificant organism. Boasting a capacity for classical and operant conditioning, the Aplysia Californica has paved new ground in understanding the mechanisms underlying memory and psychotherapy. The presence of these forms of learning, which exist in other mammals and even humans, provides researchers with valuable insights into their evolutionary history and the molecular basis of learning.

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    In addition to its exhibition of simple forms of learning, the characteristics of the Aplysia nervous system also make it conducive to research. First, Aplysia has incredibly large neurons, compared to those of humans or other animals. In fact, the only cell type in the entire animal kingdom larger than their neurons are egg cells. With neurons this large, observation and manipulation of individual cells or even organelles is feasible with modern scientific tools. Furthermore, since the Aplysia nervous system has far fewer neurons than the human nervous system, researchers have the ability to easily map circuits responsible for behaviors [2]

 

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    One particular characteristic of the Aplysia is its siphon-withdrawal reflex, which involves the structure located on the underside of the slug. Through this reflex, researchers can observe both sensitization and habituation, two simple forms of learning. Since these behavioral changes must have had a molecular basis, researchers became interested in the biology behind these behavioral phenomena.

    In the 1960s, Eric Kandel and James Schwartz began their research into the cellular mechanisms of memory formation. Realizing that Aplysia Californica would be conducive to their research needs, they began to look into the cellular mechanisms of learning in Aplysia.

    To understand what Kandel and Schwartz did, however, we must first understand classical conditioning.  Classical conditioning is defined as a learning process where two paired stimuli are repeated until the response usually evoked by the second stimuli becomes the response evoked by the first stimuli. In classical conditioning, two stimuli are used- the conditioned stimuli and the unconditioned stimuli. In the case of Pavlovian response with dogs, the conditioned stimuli would have been the bell which signaled that the food was ready, and the food itself would have been the unconditioned stimuli. If the dog salivated to the sound of the bell, then it would be evident that learning took place. The siphon-withdrawal reflex deals with similar components. When the siphon of the slug was touched “weakly”, a sharp blow to the tail or head was inflicted, thus evoking a gill withdrawal response. However, after a series of trials, the gill withdrawal response was substantially enhanced, indicating that the Aplysia “learned” that the weak touch was followed by a sharp blow [4].

    In addition to illuminating the behavioral changes behind sensitization and habituation, Aplysia researchers have elucidated the cellular mechanisms of memory formation. Research in this organism identified Cyclic Adenosine Monophosphate (cAMP) as an early signal to induce memory formation on the molecular level. Furthermore, researchers identified cAMP-dependent signaling pathway, which activates CREB (cAMP Response Element Binding Protein), a transcription factor. This then translocates to the nucleus, altering gene expression and inducing the substantial changes responsible for Long Term Potentiation [3].

    If it hadn’t done enough in terms of allowing us to understand learning a little bit better, the Aplysia has supported research from subject matters such as aging to neural plasticity to gonadotropin releasing hormone receptors [1] The avenues of research the Aplysia has opened up have left us all the more grateful to this little sea slug, and has shown the scientific community throughout the decades that big breakthroughs can come from the seemingly insignificant sea slug.


References


  1. Lodish H, Berk A, Zipursky SL, Mastidaira, P., Baltimore D., & Darnell, J. (2000). Molecular Cell Biology. 4th edition. Retrieved from: http://www.ncbi.nlm.nih.gov/books/NBK21648/

  2. Hawkins, R. D., Kandel, E. R., & Bailey, C. H. (2006). Molecular Mechanisms of Memory Storage in Aplysia. The Biological Bulletin, 210(3), 174–191. doi:210/3/174 [pii]

  3. Aplysia Genome Project. (n.d.). Retrieved from: https://www.broadinstitute.org/science/projects/mammals-models/vertebrates-invertebrates/aplysia/aplysia-genome-sequencing-project

  4. Aplysia. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/?term=aplysia

Jacob Umans

Jacob Umans


Jacob Umans is an aspiring physician-scientist in the Stanford University Class of 2020. As a cofounder of the IYNA, he is passionate about science education and hopes to share his excitement about all subfields of neuroscience -- especially glial biology and neuroimmunity -- with students around the world. He hopes to go on to earn an MD/Ph.D. after graduating from Stanford and to use his clinical experience develop a research focused on developing a better understanding of and improved therapies for neurodegenerative diseases. Outside of neuroscience, Jacob is an avid fan of puns, table tennis, and reading.

Meenu Johnkutty

Meenu Johnkutty


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