Remembering Ricardo Serrano Insausti 1954–2024

Abstract

Highly respected hippocampal neuroanatomist Ricardo Insausti died on the morning of December 26th, 2024. For the previous 2 years, he carried out a heroic battle with cancer while still teaching, collaborating, and writing. His research made huge contributions to the neuroscience of the medial temporal lobe, and he led efforts to bring consistent nomenclature to the hippocampal formation of the rodent, primate, and human brains.

As a teenager, Ricardo was part of the swimming team and enjoyed snorkeling and spearfishing when he went to the beach. He also liked Basque pelota, more as an observer than as a participant. During the weekends, he liked to play MUS, the most widely played card game in Spain that originated in the Basque country, with his older brother Jesús against his father, and his other brother Santos José. Ricardo's interest in biology was evident even as a child. But his interest in research began when he was 15 years old, when his high school biology teacher encouraged him, and other students, to do experiments and took them on field trips to, for example, collect water from puddles, which they later examined under the microscope searching for microorganisms.

He began his medical studies at the University of Navarra and early on took part in studies of the nervous system in the Department of Anatomy. He immediately fell in love with the human brain and began volunteering in the Department of Neurosurgery at the Hospital of Navarra. Two years before finishing his medical studies, he already began carrying out research for his Ph.D. on the rodent trigeminal somatosensory system, specifically investigating the pain pathways to the brainstem reticular formation, which he completed in 1978. During that summer, he worked for 3 months as a village doctor in Peralta, a small town in Navarra. Although brief, he always remembered this period of clinical service fondly.

Subsequently, Ricardo was obliged to do mandatory military service, which lasted 15 months. His service was carried out in the city of Valladolid, which is about 200 miles southwest of Pamplona. He did his service at the Military Hospital but also spent many afternoons in the Anatomy Department of the University of Valladolid, keeping up to date on scientific advances.

After he finished military service, he thought of pursuing a professional career as a neurosurgeon and combining it with basic research. To do so, he took a national exam that would allow him an internship in a hospital to specialize in neurosurgery. He passed the exam, but the Hospital of Navarra did not offer places in neurosurgery. This meant that he would have had to go to the Hospital of Zaragoza, 120 miles from Pamplona. Since he would not have been able to keep doing research at his university, he was faced with the difficult decision of pursuing being a neurosurgeon or doing research.

Ultimately, he decided to focus on basic brain research and to teach gross anatomy in the Department of Anatomy of the School of Medicine of the University of Navarra. His roots in neurosurgery were later applied in the operating room with primates and rodents for the study of the anatomical organization of memory pathways. His career was primarily focused on the connections between the hippocampus and neocortex, pathways important for memory processing. He became an Assistant Professor at this university in 1980 and was promoted to Associate Professor in 1983. During his time at the University of Navarra, his work, along with a great team of technicians, interns, and Ph.D. students, flourished.

Between 1981 and 1983, he and his family traveled to La Jolla, California, USA, to become a postdoctoral student in the Developmental Neurobiology Laboratory at the Salk Institute under the direction of W. Maxwell Cowan. During this period, he collaborated with Colin Blakemore and started a lifelong collaboration with David Amaral. With the latter, he carried out studies of the nonhuman primate entorhinal cortex that led to a series of papers defining the cytoarchitectonic boundaries and cortical and subcortical connections of the entorhinal cortex. Upon returning to Spain, he continued research on the limbic system in humans and nonhuman primates. Back in Pamplona, he started a brain bank that eventually evolved into the Human Neuroanatomy Laboratory. Ricardo pioneered a number of technical improvements in the processing of the human brain, such as postmortem vascular perfusion and standardized blocking of the brain, that led to high-quality observations of the brain and paved the way for his future collaborations dealing with harmonizing histological and MRI observations.

He returned to the Salk Institute for a sabbatical period between 1987 and 1989 with Amaral to continue the study of the structural basis of human memory systems in the nonhuman primate as well as in humans. Together they produced a chapter (The Human Hippocampal Formation) in the book The Human Nervous System, edited by G. Paxinos in 1990, which has garnered over 2000 citations. Ricardo was working on the 4th edition of this chapter at the time of his death.

In 1998, he moved to the newly established School of Medicine of the University of Castilla-La Mancha as a Professor, where he established and directed the Human Neuroanatomy Laboratory until his death. He continued to study the neuroanatomical systems that constitute the medial temporal lobe memory system. He focused much of his effort on the entorhinal cortex and attempted to bring a consistent nomenclature to this region in the rat, nonhuman primate, and human brains. For the human entorhinal cortex, he needed to add one cytoarchitectonic region beyond what was defined in the monkey brain. He called this region Middle Intermediate subfield or EMI, perhaps as a tribute to his mother, Emilia, who was known as Emi!

In 2013, Ricardo became a central figure in the Hippocampal Subfields Group (HSG), which is a harmonization effort with the goal of developing a single harmonized, reliable protocol for the segmentation of hippocampal subfields on in vivo MRI. Ricardo generously shared his time and expertise and provided expert insights and ground-truth data consisting of labeled histology sections of the medial temporal lobe. He joined numerous meetings in person and online and took enormous pride in organizing, in the summer of 2023, an HSG summit in Albacete. This highly lauded meeting provided participants with a unique, two-day hands-on course in human brain dissection and hippocampal neuroanatomy. The Albacete meeting left an unforgettable impression on all who attended it, thanks to the unparalleled enthusiasm, warmth, and generosity of Ricardo and his colleagues. Although his participation in the HSG will be sorely missed, fortunately, the scientific community will continue to be able to learn from him through several presentations available on the Hippocampal Subfields Group YouTube channel:

Webinar March 2021:

https://www.youtube.com/watch?v=KQRUNOn0VpQ.

Podcast Sep 2023:

https://www.youtube.com/watch?v=AQHVbHGMLNY&t=25s.

Albacete meeting June 2023:

Over the past decade, Ricardo also collaborated with computational researchers to develop detailed probabilistic brain atlases. From 2014 to 2018, he worked with Juan Eugenio Iglesias to create a probabilistic atlas of thalamic nuclei using serial histology and postmortem MRI. In 2015, he launched an NIH-funded collaboration with Paul Yushkevich, Laura Wisse, and colleagues at the University of Pennsylvania to map anatomical variability in the medial temporal lobe and the 3D distribution of Alzheimer's pathology. The project introduced novel techniques, including in situ brain perfusion to minimize postmortem deformation and 3D-printed molds for MRI-histology alignment. Ricardo personally annotated cytoarchitectural boundaries on thousands of whole-slide histology images, creating the world's most comprehensive dataset of medial temporal lobe anatomy, which will be made publicly available to preserve his unparalleled expertise. He was deeply engaged in this project, making several visits to Philadelphia and raising awareness in Spain about brain donation's role in Alzheimer's research through television and media outreach.

In addition to his prodigious research efforts, he was also a dedicated mentor; he was a Ph.D. thesis advisor to more than 25 students, mostly dealing with the human temporal lobe. Two of these students, Monica Muñoz and Mar Ubero, returned to the Human Neuroanatomy Laboratory and, together with the group Ricardo created with Emilio Artacho, Pilar Marcos, and Maria del Mar Arroyo, benefitted from Ricardo's ongoing guidance.

Ricardo had many interests and loves beyond neuroanatomy. He loved most of all his family and enjoyed camping trips when they could get out into the country. He also loved relaxing with his pipe while listening to classical music and reading a paper or a book. Ricardo loved to read about a wide variety of subjects from philosophy to history or music, and he always took advantage of the SfN Meeting to visit all the booths on Publishers Row to look for new books.

For those who knew and loved Ricardo, his passing still does not seem real. Some solace is taken in the fact that he lives on in his children and grandchildren, his writings, and, more recently, his videos on YouTube. He will be missed by many.

He is survived by his wife, Maria Carmen; his sister, Ana; and brother, Jesús; his children, Arantxa, Begoña, Cristina, and Mikel; and his grandchildren, Idoya, Carolina, and Guillermo.