A reductionist approach to understanding the nervous system: the Harold Atwood legacy

This special issue of the Journal of Neurogenetics honors the career of Professor Harold Atwood and his contributions to the field of neurophysiology. Harold completed his undergraduate degree in Biology at University of Toronto in 1959. He went on to do a M.A. at the University of California, Berkeley with R.I. Smith and then a Ph.D. in 1963 working with C.M. Yonge and G. Hoyle at University of Glasgow. Subsequently, he did postdoctoral studies at University of Oregon with G. Hoyle and at Caltech with C.A.G. Wiersma. He obtained a faculty position in Department of Zoology at University of Toronto in 1965. In 1981, he was recruited as the Chair of the Department of Physiology in the Faculty of Medicine at University of Toronto. He would later form the Medical Research Council of Canada Research Group in Nerve Cells and Synapses, directing it until 2000. He retired in 2002 at age of 65 years, but kept his laboratory running until 2008. Over the course of his career, he trained numerous graduate students and postdocs/research associates, many of whom have gone on to develop their own research programs (see Figure 1 for an Atwood scientific family tree). In addition, many visiting professors did sabbaticals in the Atwood lab (Table 1).

Figure 1. Harold Atwood scientific family tree.

Table 1. Sabbatical visitors to the Atwood lab.

Year	Name	University
1973	W.M. Pastor	McGill University
1984	R.A. Webb	York University
1986–1987	M. Schiebe	University of Ulm
1985, 1987	I. Parnas	Hebrew University
1985	H. Parnas	Hebrew University
1989, 1990. 1991, 1992, 1999, 2001, 2003, 2005	H. Bradacs	University of Graz
1999–2000	M.B. Sokolowski	York University (currently – University of Toronto)
1999–2000	I. Brown	University of Toronto
2000	R.M. Robertson	Queen’s University

Harold’s research program used a reductionist approach to understand the nervous system, taking advantage of relatively large readily accessible nerve terminal endings. He and his trainees used a combination of ultrastructural and physiological analyses to provide an understanding of how nerve cells and their synapses respond to experience and activity. Much of his early work was done with crustacean neuromuscular junctions (nmj). Important discoveries included long-term facilitation (Sherman & Atwood, 1971), the existence of silent synapses (Jahromi & Atwood, 1974; Wojtowicz, Smith, & Atwood, 1991), a requirement for protein synthesis in long-term adaptation (Nguyen & Atwood, 1990), activity-induced changes in the number of active zones (Wojtowicz, Marin, & Atwood, 1994) and differential calcium sensitivity of neurotransmitter release at phasic and tonic synapses (Millar, Zucker, Ellis-Davies, Charlton, & Atwood, 2005).

In 1991, Harold did a sabbatical in Chun-Fang Wu’s lab at the University of Iowa. It was during this time he first became acquainted with the Drosophila larval nmj. This encounter would be quite impactful for both Harold and the Drosophila larval nmj preparation. In subsequent years, Harold would focus much of his research program on the Drosophila larval nmj. He and Bryan Stewart, a PhD student at the time, would continue the initial findings from the Wu Lab to develop an improved saline that would allow for prolonged electrophysiology experiments (Stewart, Atwood, Renger, Wang, & Wu, 1994). This would greatly enhance the use of the Drosophila larval nmj to understand synaptic function. Collaborations with Chun-Fang Wu would also demonstrate that muscle fibers 6 and 7, commonly used by many Drosophila physiologists, were innervated by two types of axons that result in type 1b and type 1s boutons, which differ in both their morphological and physiological properties (Atwood, Govind, & Wu, 1993; Kurdyak, Atwood, Stewart, & Wu, 1994). In subsequent years, other important findings included altered morphological parameters of nerve terminals functionally compensating for genetic perturbations (Stewart, Schuster, Goodman, & Atwood, 1996), variation in quantal size at the Drosophila nmj (Karunanithi, Marin, Wong, & Atwood, 2002) and improved calcium imaging protocols (Macleod et al., 2002). Harold and his students would also show important roles for proteins such as Cysteine string protein (Dawson-Scully, Bronk, Atwood, & Zinsmaier, 2000) and Frequenin (Dason et al., 2009) in synaptic function.

The special issue contains a combination of perspective, review and original research articles by six former Atwood lab postdocs/research associates (Milton Charlton, Martin Wojtowicz, Joffre Mercier, Greg Lnenicka, Robin Cooper and Gregory Macleod), five former Atwood lab PhD students (Frederick Tse, Peter Nguyen, Bryan Stewart, Ken Dawson-Scully and Jeffrey Dason), and four close collaborators (Chun-Fang Wu, Marla Sokolowski, Ian Meinertzhagen and Alberto Ferrús).

We are particularly delighted to open the issue with a piece called ‘Child Harold’ by Harold Atwood’s sister (Margaret Atwood) which describes Harold’s early and formative years (Atwood, 2018). Next, Milton Charlton provides a perspective article on Harold’s academic career, research highlights and Milton’s personal experiences with Harold that span 50 years (Charlton, 2018). Martin Wojtowicz then provides an account of his time in the Atwood lab, highlighting some of their scientific discoveries and people that were in the lab at the time (Wojtowicz, 2018). Robin Cooper describes his first meeting with Harold and a personal account of his time in the Atwood lab (Cooper, 2018).

The next set of articles consists of four review papers. Ian Meinertzhagen provides a review on the Drosophila visual system (Meinertzhagen, 2018). Alberto Ferrús et al. provide a review of the molecular mechanisms of synapse dynamics (Mansilla et al., 2018). Peter Nguyen and Jennifer Gelinas review the roles of β-adrenergic receptors in modifying ion channels, glutamatergic AMPA receptors, and translation initiation factors during LTP (Nguyen & Gelinas, 2018). Joffre Mercier et al. provide a review article on the use of the Drosophila larval nmj as a model system to understand how synapses are modulated by neuropeptides (Ormerod, Jung, & Mercier, 2018).

The next six papers are original research reports using the Drosophila larval nmj. Chun-Fang Wu and Xiaomin Xing describe the inter-relationships between physical dimensions, distal-proximal rank orders, and basal GCaMP fluorescence levels in functionally distinct synaptic boutons (Xing & Wu, 2018). Greg Lnenicka et al. examine the effects of parvalbumin on synaptic development and physiology (He, Nitabach, & Lnenicka, 2018). Bryan Stewart et al. report a role for postsynaptic Syntaxin 4 in the negative regulation of presynaptic neurotransmitter release through a retrograde signaling mechanism (Harris, Littleton, & Stewart, 2018). Jeffrey Dason et al. characterize the role of a Type II phosphatidylinositol 4-kinase in synaptic function (Cantarutti, Burgess, Brill, & Dason, 2018). Gregory Macleod et al. describe novel ‘kisser’ probes for resolving the distribution of membrane proteins (Stawarski, Hernandez, Justs, & Macleod, 2018). Ken Dawson-Scully et al. report a role for BK channels in tolerance of synaptic transmission to acute oxidative stress (Bollinger, Sial, & Dawson-Scully, 2018).

We have two additional original research reports, one by Marla Sokolowski et al. using a promoter analysis strategy to demonstrate that the Drosophila foraging gene’s complex modular structure allows for independent promoter regulation of foraging’s larval feeding-related phenotypes (Allen et al., 2018). Second, we have a paper by Frederick Tse et al. showing that strong stimulation can trigger full fusion and slow endocytosis of small dense core granules in rat carotid glomus cells (Tse et al., 2018).

Lastly, we provide a photo gallery of the many different eras of the Atwood lab (Dason, Hegström-Wojtowicz, & Sokolowski, 2018). Harold had a profound impact on the field of neurophysiology. This is evident by both his scientific discoveries and by the number of his scientific progeny that have continued in research and developed their own research programs (Figure 1), in many cases, heavily influenced by their time in the Atwood lab. With this special issue, we thank Harold Atwood for his many scientific contributions and his lasting influence on all his former trainees and collaborators.

Acknowledgements

JSD: I would like to thank Prof. Harold Atwood for the privilege of working in his lab and the honor of being his last graduate student. In addition to being a great scientist, he is also an excellent and caring mentor. He always wanted to see his students do well and did everything he could to help them succeed. Even after finishing my PhD, he has continued to help me by critiquing my manuscripts, helping with job applications for faculty positions and more recently reading my grants. I was very fortunate to have him as a supervisor and I feel like he had a profound effect on my career.

MBS: It is an honor and privilege to call Harold Atwood my friend. I remember the first time that I saw him in the 1970s walking along the halls of University of Toronto’s Ramsey Wright Zoological Laboratories in his white lab coat. The students who pointed him out to me were amazed that he was a professor because he looked like he was 16 years old. I was 18 years old at the time. Then in 1981 during the last year of my PhD I remember hearing that Dr. Atwood was leaving our department to become the Chair of the Department of Physiology in the Faculty of Medicine at the University of Toronto. I learned that he was a much admired Chair. Ten or more years later I was a professor at York University in Toronto and I remember picking up the phone and Harold was on the line. I knew him by reputation (of course) but this was the first time that I had ever spoken with him. He told me about his sabbatical with Chun-Fang Wu and his excitement about the Drosophila nmj. With humour in his voice, he told me that he had been asking scientists, “who might know about larval behaviour”? “Sure enough (he said) all roads led to me, which was quite convenient because I was literally down the road.” Our first meeting was full of talk about Drosophila larvae and mostly I was talking and Harold was smiling and nodding. I remember phoning Ian Meinertzhagen and describing Harold and my first meeting. I asked Ian whether he thought that I had talked too much. I heard Ian laugh heartily and ask “have you met his delightful wife Lenore?”. Harold and I soon became good friends and I stopped worrying about filling the silences. I did a sabbatical in his lab in the late 1990’s at which time he encouraged me to return to the University of Toronto, a decision I have never regretted. I have learned many things from Harold: how to write a research grant without qualifying every statement (“Marla you don’t need that information”), how to think like a neuroscientist, and finally, the utmost importance of having a weekly “cake day”. Harold is exceedingly generous, fair, honest, ethical and also very particular about how science needs to be done. In his retirement years he leads the Senior College at the University of Toronto, a vibrant group of retired professors who regularly meet for lectures and discussions. My husband Allen and I meet Harold and Lenore for dinner at a Chinese buffet restaurant (yes you heard that right-Harold who ate a yogurt and apple for lunch every day when his watch alarm went off -prefers to go to an all you can eat buffet!). I am so grateful to have Harold as a friend and colleague. It was a pleasure to edit this volume in his honor with Jeff Dason and Chun-Fang Wu.

Disclosure statement

No potential conflict of interest was reported by the authors.