The Board of Directors of the Zoological Society of Japan (a public interest incorporated association) held a board meeting on Friday, June 2, 2018, and deliberated on the award recipients based on the recommended candidates from the Award Selection Committee. As a result, the recipients of the 2017 Zoological Society of Japan Awards have been decided as follows. The award ceremony, as well as the lectures by the winners of the Zoological Society Award and the Encouragement Award, will be held on September 22 at the Toyama Prefectural Civic Center.

Public Interest Incorporated Foundation, Zoological Society of Japan
Chairman Yoshitaka Oka

Zoological Society of Japan Award

Etsuro Ito
Waseda University, Faculty of Education and Integrated Arts and Sciences, Professor
Elucidation of the learning and memory mechanisms in molluscan gastropods

Reason for winning

Dr. Etsuro Ito has studied the learning and memory mechanisms of molluscan gastropods for many years. In this field, which has a tradition dating back to Kandel, Dr. Ito was the first to select the pond snail as a subject and has pursued highly unique research utilizing its conditioned taste aversion behavior. A major recent achievement is the clarification that insulin-like substances play a decisive role in the formation of long-term memory in conditioned taste aversion. The smooth progress of this series of studies on the relationship between memory and insulin-like substances is underpinned by Dr. Ito's exemplary, vast, and meticulous quantitative research, beginning with the discovery of a neuron known as the Cerebral Giant Cell (CGC), for which he received the Zoological Society of Japan Award for Young Scientists in 1999. Dr. Ito developed apparatuses for quantitatively analyzing the CREB gene and its gene products in a single CGC neuron, successfully applying them to his own research and achieving accomplishments well-fitting for the Zoological Society of Japan Award.

Winner Summary

My initial motivation for using gastropod mollusks as experimental animals came from studying abroad as a Visiting Fellow in Dr. Daniel Alkon's laboratory at the US NIH, where I worked with sea slugs (Hermissenda) when I was given the opportunity to engage in learning and memory research. Furthermore, I consider myself truly fortunate to have been able to immerse myself in a deeply stimulating environment and era during my late twenties and early thirties—such as conducting extremely intensive research at the Marine Biological Laboratory in Woods Hole and engaging in fierce exchanges at the Society for Neuroscience (SfN) annual meeting (Itoet al., 1994, J. Neurochem.）。

After returning to Japan in 1993 (Heisei 5) upon obtaining a position in the Faculty of Science at Hokkaido University, while I was wondering which experimental animal to use, Professor Akio Urano, who was a professor in my department, suggested the pond snail (Lymnaeaintroduced ) to me.Lymnaea stagnalisis called the great pond snail in English and Europa-monoaragai in Japanese. The most distinctive feature of the pond snail is that its metamorphosis is completed inside the egg, meaning that upon hatching, it is already a miniature version of the adult. Since sea hares and sea slugs undergo metamorphosis even after hatching, keeping them is quite troublesome, and experiments must be started by collecting adults. However, in the case of the pond snail, it is possible to complete the life cycle in one's own laboratory, allowing for year-round research (the research results on the pond snail were firstZool. Sci.The paper presented at: Kojimaet al., 1996, Zool. Sci.）。

When presented with the preferred tastant sucrose followed by the aversive potassium chloride or an electric shock, the pond snail Lymnaea ceases to perform the feeding movements normally elicited by sucrose. We considered this to be a form of "conditioned taste aversion." Conditioned taste aversion in Lymnaea is a "long-term memory" that, once acquired, persists for a long period of over one month. Subsequently, through a series of physiological and histological studies on this conditioned taste aversion, I was awarded the Young Investigator Award of the Zoological Society of Japan in 1999 (Heisei 11) (Review article at the time of receiving the award: Itoet al., 1999, Zool. Sci.）。

After that, in order to clarify which genes are expressed after the formation of long-term memory, we created our own pond snail DNA microarray and conducted repeated research. Regarding the creation of this pond snail DNA microarray, Professor Kaoru Azumi was at Hokkaido University at the time, and our collaborative research with Professor Azumi had a major influence. Looking back at that time, "comprehensive screening" was a trend. As a result of that research, we were able to reveal that gene expression of molluscan insulin-related peptide (MIP) is upregulated in the brain after learning. Honestly, however, at that time we were unable to understand the biological significance of this upregulation of insulin-related peptide expression (Azamiet al., 2006, J. Neurosci. Res.）。

In 2006 (Heisei 18), I moved from Hokkaido University to the Faculty of Pharmaceutical Sciences at Tokushima Bunri University, Kagawa, and after that relocation, I investigated the effects on the neural circuits involved in masticatory movements by directly administering insulin-like peptides to isolated brains. When pond snail insulin-like peptides or mammalian insulin were administered, "long-term potentiation"-like responses were confirmed in specific neural circuits involved in masticatory movements. Long-term potentiation is generally considered to be the neural basis of learning and memory, meaning that it was found that insulin-like peptides, which are involved in regulating blood sugar levels in the body, also play an important role in the conditioned taste aversion learning mechanism in the pond snail's brain. Furthermore, focusing on the fact that the structure of the insulin receptor binding site is homologous between pond snails and mammals, when mammalian antibodies targeting that binding site as an epitope were injected, this long-term potentiation-like response was abolished. In addition, injecting the antibodies into individuals also inhibited the long-term memory formation of conditioned taste aversion. Thus, the necessary and sufficient conditions for insulin-like peptides in the conditioned taste aversion learning mechanism were established (Murakamiet al., 2013, J. Neurosci.）。

On the other hand, we knew from experience that pond snails placed in a mildly starved state show good performance in conditioned taste aversion learning, whereas learning memory is not established in a severely starved state. Therefore, as a working hypothesis, we predicted that the concentration of insulin-like peptides would be low under severely starved conditions. Indeed, when we injected insulin-like peptides into severely starved pond snails to raise their concentration, we found that their learning memory performance was improved. Thus, it became clear that insulin-like peptides hold the key to the learning and memory mechanism. Furthermore, we approached the question of whether pond snails placed in a severely starved state truly fail to acquire conditioned taste aversion learning. Therefore, after trying various conditions, we discovered that when severely starved pond snails undergo conditioned taste aversion learning, are then kept in a well-fed state for a while, and are subsequently returned to a starved state, surprisingly, the conditioned taste aversion learning is established. Put simply, conditioned taste aversion learning is learning in which "one can no longer eat favorite things because a punishment is given"; in other words, if an animal is extremely hungry at the time of learning, even if it has learned, it will eat things it should not eat because "desperate times call for desperate measures." Then, when it becomes hungry again some time later, it recalls the conditioned taste aversion learning and refrains from eating things it should not. Furthermore, memory recall was possible by administering insulin-like peptides instead of this secondary starvation. In short, it was found that animals do not use the learning and memory mechanism in a single stereotyped manner, but rather utilize it flexibly to ensure individual survival (Itoet al., 2015, J. Exp. Biol.）。

In 2016 (Heisei 28), he moved to the Department of Biology, Program in Educational Sciences, School of Education at Waseda University, where he began developing new research. At present, he has succeeded in fully automating the learning apparatus and has also clarified the relationship between starvation states, learning performance, and changes in monoamine concentration (Aonumaet al., 2017, Neurobiol. Learn. Mem.). Research is also being conducted on regional differences in learning capacity (differences by country).

I am deeply grateful that receiving this academic award is the result of the guidance and cooperation of mentors, fellow researchers, graduate students, undergraduate students, postdoctoral fellows, technical assistants, secretaries, and numerous domestic and international collaborators during my time at the US NIH, Hokkaido University, Tokushima Bunri University, and my current institution, Waseda University. In addition, I am keenly aware that the over-century-long history of biological research using pond snails undoubtedly propelled our research forward. For example, insulin-like peptide (MIP) was discovered when it was first proven that insulin-like peptides also exist in invertebrates, and it was a researcher at the aforementioned Vrije Universiteit Amsterdam who discovered it. In other words, I strongly feel that research is passed on indefinitely, and I am deeply grateful to those who came before us.