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BIOGRAPHICAL MEMOIRS

Richard Freeman Mark 1934–2003

Introduction Early life and undergraduate years France United States of America Monash University Australian National University Scientific work Nerve regeneration and synaptic mechanisms Memory formation Sensory pathway development and central plasticity Contribution to professional societies Australian Neuroscience Society Other interests Conclusions Acknowledgments References Bibliography

By P.M.E. Waite and L.J. Rogers

This memoir was originally published in Historical Records of Australian Science, vol.17, no.1, 2006.

Numbers in brackets refer to the bibliography at the end of the text.

Richard Freeman Mark was born in New Zealand and studied Medicine at Otago University, followed by doctoral studies at the Université d’Aix-Marseille in France. He undertook postdoctoral studies at the Californian Institute of Technology before accepting a Senior Lectureship at Monash University, Melbourne. His research interests focused on neuroscience, with cutting-edge studies on memory, nerve regeneration, neurodevelopment and plasticity. Richard was appointed to the Foundation Chair of Behavioural Biology at the Australian National University in 1975 and remained there for over twenty-five years. He championed an interdisciplinary and integrated approach to neurobiology in both teaching and research. He was a gifted supervisor and teacher and and initiated the first honours Neuroscience course in Australia. He was elected to the Fellowship of the Australian Academy of Science in 1974, served as President of the Australian Neuroscience Society from 1998–1999 and was awarded the Centenary Medal in 2003.

Richard Mark was born in New Zealand on 11 August 1934, and died in Canberra, Australia, on 13 August 2003. He married Gerda Fischel in 1958 and they were together until 1975. They had two children, Bettina (born 22 April 1966) and David (born 3 August 1967). For the past three decades he shared his life and conducted research with his partner, Dr Lauren Marotte.

It would be incomplete to discuss only Richard’s scientific achievements since, although he was foremost a scientist, his exceptional imagination extended to the arts – in word and music. He was convinced of continuity between the sciences and the arts and had the rare talent and perception to practise science with accuracy and precision and as an art. In doing so, he brought breadth, creativity and brilliance to the many areas of research to which he contributed so much. Richard had a way of seeing well beyond the ordinary and he reached out to understand the ‘big’ questions, believing that it was better to address the important questions in science rather than to ask only small questions of lesser importance that can be solved more easily. By tackling some of the essential relationships between brain and behaviour, he put that philosophy into practice.

At Monash University he set up his own laboratory working on such wide-ranging issues as nerve regeneration, visual perception, developmental plasticity and the mechanisms underpinning memory. A key feature of Richard’s approach was to maximize the opportunities offered by unusual animal models; species he studied at that time included axolotls, fish, frogs and chicks, as well as humans. Projects included competitive reinnervation of muscle in fish and axolotl and drug inhibition of memory formation in young chicks. All of this work was at the forefront of the field internationally with publications in both Nature and Science. These studies led to the idea that competitive interactions between nerve terminals could result in synaptic repression, without necessarily having recognisable changes in ultrastructure. Such ideas were radical at that time but have now become mainstream.

In 1975 Richard was invited to take up a foundation chair to establish the Department of Behavioural Biology at the Australian National University (ANU). This became the Developmental Neurobiology group in 1988 and Richard headed this group from 1992 until his retirement in 1999. Under his guidance a lively department was established in the Research School of Biological Sciences. Richard’s own work involved establishing a breeding colony of tammar wallabies and using them as a model species, initially to study development of the visual pathways. Later this was extended to developmental studies of the auditory and somatosensory systems. Aided by the accessibility of the developing pouched young, he was able to use techniques impossible in eutherian mammals. Hence, he was able to conduct a series of fundamental experiments that took advantage of the marsupial model, and thereby to extend his important research on development of the nervous system. Much of this research was conducted in collaboration with other ANU researchers, as well as scientists from other universities in Australia and overseas.

In 1976 Richard was invited to deliver the G. E. Rennie Memorial Lecture and was awarded the G. E. Rennie Medal by the Royal Australasian College of Physicians. He received the Peter Aitken Medal from the South Australian Museum in 1992. He was elected to the Fellowship of the Australian Academy of Science in 1974 and served on its Council from 1984 to 1987. From 1998 to 1999 he was President of the Australian Neuroscience Society, in which capacity he fostered links between basic science and clinical medicine and recognised the public need for scientists to explain their work to non-specialists. In addition to being an excellent researcher, Richard was a stimulating and much respected teacher. He received the Centenary Medal in 2003 for service to Australian society and science in developmental neurobiology.

Early life and undergraduate years

Richard’s paternal grandfather emigrated from Northern Ireland to New Zealand and settled in Kati Kati on Tauranga harbour. The maternal side of Richard’s family came from Britain and France and they settled in the Chatham Islands about 500 kilometres to the east of New Zealand.

Richard was the eldest of three children born to Dr John Mark, a highly respected surgeon in Tauranga, and Kate Fougere Wishart. His sister Sally was born in 1937 and his younger sister, Belinda, in 1942.

After attending the local Tauranga primary school until he was 9 years old, Richard was sent to boarding school, first to St Peters primary school in Cambridge, New Zealand, and then, when he reached secondary school, to Wanganui Collegiate, New Zealand, until he was 16 years old. At St Peters he enjoyed singing in the choir and he took up rowing at Wanganui, winning a ‘Blue’. However, he found the years of boarding school, in his own words, ‘unbearably miserable’ because he suffered a good deal of bullying. As a consequence of this austere schooling, he had no indication that he was intelligent until he went to the University of Auckland at the young age of 17 years. Here he lived in O’Rourke Hall, made many friends and became interested in science. He topped the examinations at the end of his first year and gained entry to medical school. Competition was fierce, and only 17 of a total class of around 130 gained the necessary qualifying grades.

Richard transferred to the University of Otago in Dunedin and enrolled in Medical School, initially at Selwyn College, thus following in the footsteps of his father, who had been a medical student at the same college. Photographs of his father in the class of 1922 were hanging on the college walls. Dick Barnett, one of Richard’s fellow students and an old friend, recalls that period of their lives in the following words:

Richard’s medical studies, including two additional years doing research, were completed in 1959, when he also received a prize in clinical surgery. So passionate did he become about research from his very first exposure to it that he extended the usual single year away from his medical course for a further year and completed a Masters in Medical Science in 1956. The topic was synaptic transmission in the cat spinal cord. This degree was undertaken in the Physiology Department of the Medical School, under the supervision of Archie McIntyre. The work followed on from earlier investigations begun by Professor (later Sir) John Eccles during his time at the Otago Medical School (1944–1952).

Richard was awarded MB ChB and MMedSci by the University of Otago. While in Dunedin he met Gerda Fischel, a microbiology student, and they married in 1958 in Auckland, where Richard was working in Obstetrics and Gynaecology at the National Women’s Hospital.

Professor Archie McIntyre was his mentor in New Zealand and later Richard would join him at Monash University. Richard’s early research was in the field of neurophysiology and his career began spectacularly with a paper in Nature on multiple firing at central synapses. He also published papers on afferent cutaneous nerve fibres in the cat and contraction of uterine muscle. These excellent early papers made a very promising beginning to a career that was to continue at the forefront of neuroscience research.

France

In 1959 Richard was awarded a Wellcome Trust travel grant to undertake postgraduate research in medicine, and he decided to study in France. He prepared for this venture by learning the French language – listening to gramophone records in the evenings and attending tutorials taught by one of the very few French people in Auckland at that time.

As a young couple, Richard and Gerda left New Zealand for France in 1960. Richard recalled the sea voyage to Europe as great fun. They disembarked in Naples, where Richard visited the Stazione Zoologica and met the famous English professor of anatomy, J. Z. Young, who became his life-long supporter.

In France, he conducted research at the Université d’Aix-Marseille with Jacques Paillard on the effect of muscle stretch on the modulation of spinal excitability in humans. His thesis on this topic, written in French, gained him a Doctorat de Troisième Cycle, and it is a work that is still quoted frequently.

Apparently, Richard chose to work on humans in a non-interventional way after his Dunedin studies on anaesthetised cats. He loved cats and did not like to operate and experiment on them and then to euthanase them.

Jacques Paillard remembers Richard’s time in his laboratory as one of much humour and pleasant sociability. He said Richard worked hard and methodologically, remaining in the laboratory until late at night, and soon gathered a great amount of new and interesting data. Jean‑Marie Coquery was a student of Jacques Paillard at the same time as Richard and they published together on several occasions.

United States of America

From 1962 to 1966, Richard held a Research Fellowship in Biology at the California Institute of Technology, Pasadena, where he worked with R. W. Sperry on hemispheric specialization, studying split-brain monkeys, and on regeneration of neuromuscular connections. It was here that he began to develop his interests in neuroembryology and mechanisms of behaviour. He valued this time enormously and it laid the basis for his life’s work in research in developmental biology.

Richard was in Sperry’s laboratory from August 1962 to August 1966 and worked closely with many colleagues who became good friends also. A collaborator, Mike Gazzaniga, recalls ‘His extreme brightness, the maverick in his soul always kept everyone in Sperry’s lab on their toes’. The Californian years were an exciting time professionally and also politically. They encompassed the Watts riots (11 August 1965) and the awakening of the civil rights movement.

Monash University

While Richard was working in Sperry’s laboratory in California, Archie McIntyre visited and persuaded Richard to come to Australia to join him at the new Monash University, where he had become Foundation Professor of Physiology.

In 1966, Richard accepted a senior lectureship in Physiology at Monash University. He was promoted to Reader in Physiology in 1970 and remained at Monash until 1974. There he established a laboratory with excellence in electrophysiological techniques as well as neuroanatomy and the study of animal behaviour. During his time at Monash University he produced some of his most important findings about the ability of damaged nerves to grow back and reconnect by processes of synaptic recognition and competition. Much of this research was carried out on the connections between nerves and muscles in lower vertebrates, especially fish, but he also looked at nerve regeneration and innervation in frogs and axolotls. His ideas on synaptic competition and selection were groundbreaking and became widely accepted. He also became interested in the cellular processes involved in memory formation and proposed a role for the sodium–potassium ATPase pump in the transition of shorter- term to longer-term memory.

Richard Mark in his laboratory at Monash University in the late 1960s. [Photographer: Diana Dorrington (née Harrison)]

Richard also hypothesised that memory formation involved the suppression of synaptic activity in unstimulated nerve pathways, which was a radical break from the then-held view that memory formation involved only the facilitation of synaptic transmission in stimulated pathways. These ideas and others related to memory formation are covered in his book entitled Memory and Nerve Cell Connections (43). This book is also a fine example of Richard’s exceptional ability to write science engagingly and with the flair of an artist.

Ray Johnston was Richard’s first postgraduate student. Together they began by measuring neural activity in the tectal commissure of goldfish. Only grouped nerve activity could be measured but, one day, the electrode gave what appeared to be disturbing results – spikes popping up here and there. Ray went to adjust the electrode but Richard stopped his arm and said, ‘Don’t do that’. It was their first recording from a single unit. Ray was slightly annoyed because it meant a big change in the direction of the work, but Richard was happy. He was, of course, quite right. He was never fazed by an experimental result and frequently astonished collaborators with the breadth of his knowledge and the way he could apply it to something they had just observed. Unexpected experimental results seemed never to bother him. Often he would show that they were simply pointing in an unexpected and exciting direction.

Marie Gibbs, who studied the biological basis of memory formation, was another of Richard’s postgraduate students at Monash University. Lauren Marotte also joined Richard’s research group as a postgraduate student and published with him during this time. She worked with Richard on regeneration of nerves to fish eye muscles and they established a life-long research collaboration and partnership.

Others who started working with Richard at Monash University included Joan Schramek, who conducted electrophysiological experiments on regeneration of sensory fibres to skin, and one of the authors of this memoir, Lesley Rogers, who investigated memory formation and brain development using the chick as a model.

Australian National University

Richard was appointed to the Foundation Chair in the Department of Behavioural Biology within the Research School of Biological Sciences (RSBS) at the ANU in 1975. The new department joined several others in RSBS conducting research on topics as diverse as molecular biology, genetics, protein biochemistry, neurobiology, taxonomy and bioenergetics, as well as developmental, environmental and population biology. Founded in 1967, one of the early recommendations for RSBS was ‘to establish a centre of research into problems of basic biological concern which have largely been neglected in Australia’ (RSBS Annual Report 1977). It was envisaged that approaches would range from molecular and cellular to populations and behaviour and where possible should exploit the special features of Australian biota. The new Behavioural Biology group, under Richard’s guidance, aimed to find out ‘to what extent animal and human behaviour can be understood in terms of current knowledge of the anatomy, physiology and biochemistry of the vertebrate brain’ (RSBS Annual Report 1975, p. 2).

In his application for the position of Chair, Richard wrote: ‘The analysis of mechanisms of behaviour in terms that are meaningful to neurophysiology is the thing I found most fascinating’. He believed that a strong grounding in biology and physiology was likely to be fruitful for elucidating behavioural mechanisms. His approach was to look for situations in which ‘the behaviour is readily elicited and may be studied quantitatively’ and reasonable hypotheses of the physiological mechanisms tested. He further proposed that anatomical, physiological or pharmacological manipulations of the brain could then be carried out to test whether they influenced the behaviour in a way predicted by the physiological theory.

The RSBS initially occupied timber buildings, built to house nursing staff of the old Canberra Hospital. By 1977 most of the departments had moved to a purpose-built facility but Behavioural Biology remained in the older building, which despite renovation was really inadequate for modern research. In fact Lauren Marotte recalls that there were regular plagues of mice, which had a taste for the insulation on the electrical wiring of laboratory equipment. Despite this and other obstacles, the department grew rapidly and within four years supported approximately twenty research and technical staff and visiting fellows. Richard enjoyed the interdisciplinary and co-operative approach and built around him a team skilled in neuroanatomy and neurophysiology, neurochemistry and animal behaviour. In 1978, over 25 projects were underway working on preparations as diverse as chickens, pigeons, axolotls, goldfish, rats and humans. Early research themes included nerve regeneration, the development and maintenance of neural connections, the biochemistry and behaviour of the developing visual system, and the pharmacology of learning and memory.

Richard’s integrated approach to studying neural function was at the forefront of neurobiological thinking at that time. In Europe and the USA, the 1970s saw the fledgling discipline of neuroscience gaining increasing recognition. Incorporating all the parent disciplines of neuroanatomy, neurochemistry, neurophysiology and neuropharmacology, neuroscience brought the diverse approaches and interests under one banner. The first meeting of the Society for Neuroscience in the USA was held in 1971 and, one year later, a group of Australian neuroscientists also started informal meetings, although the Australian Neuroscience Society (ANS) was not formally inaugurated until 1981 (Redman 1992). The Department of Behavioural Biology, with its integrated and contemporary approach to neuroscience, was a Mecca for young researchers from around Australia in addition to top international visitors from the USA, Europe, the Middle East and Asia.

Richard had a particular affinity for graduate teaching and supervision of research students and early-career postdoctoral students. Many of his students describe his lectures on neuroscience as inspiring and a break from traditional ways of teaching the subject. He believed in the importance of trying to select techniques in areas of research that matched the special abilities and interests of particular students, rather than assigning projects according to the immediate needs of a programme. A past postdoctoral student and subsequent colleague, Michael Ibbotson, recalls:

Richard also had a particular ability to make students feel valued. As Cathy Leamey, then a young PhD student from Sydney, notes: ‘the group which Richard had set up provided an environment of respect and trust, scholarship, resources and intellectual and motivational support where a student could really flourish’. Richard was always gently guiding and encouraging and he was always approachable and available. Students remark that he was able to guide and teach without being condescending or didactic. Michael Ibboston remembers his collegial approach to leadership and tells of an occasion when he was practising a seminar in front of Richard and asked him whether he would like to be referred to as Professor Mark when the full audience was addressed. Richard replied: ‘Certainly not. My title just tells people I’ve still got a job. Just call me Richard.’ His witty sense of humour and quick retort are remembered by colleagues, family and friends.

In 1979 the New Initiatives Program at the ANU approved an application from Richard for a new facility: the establishment of a colony of tammar wallabies (RSBS Annual Report, 1979). Richard foresaw the potential advantages of marsupials, with their period of accessible extra- uterine development, for studies on mammalian neuroembryology (reviewed in [90]). Years later, in an internal grant application, Richard was to explain his reasoning for the marsupial colony in the following way:

During the early to mid-1980s Richard’s interests in the visual system expanded considerably to include structural and ultrastructural studies as well as biochemical and electrophysiological research on the retina and central pathways. In addition his Department was involved in the newly emerging field of neuroethology, on specialized species behaviours, reporting on visual acuity in birds of prey, depth perception in pigeons and seed husking in parrots. A major commitment was made to the development of the visual pathways in the wallaby as a prelude to studies on plasticity. Besides this research on vision, Richard’s interest in the control of limb musculature continued with projects on cell death of motoneurons and the factors that regulate muscle size. Yet another avenue of research focused on hearing and localization of sound direction in birds and bats.

In 1983 Richard’s proposal (together with Drs I. Morgan and F. Bygrave) for a new undergraduate honours course in Neuroscience was implemented. The course was open to any graduate with a three-year science degree. Interdisciplinary in approach, the course consisted of a series of lectures and practical classes, plus the opportunity to undertake short research projects. It was designed and taught as a joint venture between staff in RSBS and the John Curtin School of Medical Research. While similar programmes were on offer at Harvard, Stanford and the State University of New York, this was the first undergraduate Neuroscience course in Australia (ANU Reporter 1982). The programme proved so successful it was adopted as a model for other honours courses.

The mid to late 1980s was a difficult period for Richard and his group as funds were short and laboratory conditions poor. The move to the new building, foreshadowed at the time of Richard’s appointment, was taking much longer than anticipated. A comprehensive review of RSBS undertaken in 1987 recommended rationalization of departments based on common interests and approaches. The aim was to achieve increased flexibility to expand or contract according to performance, research priorities and opportunities, and to spread the administrative loads by allowing group leaders to change from time to time (RSBS Annual Report 1989). As a result of this reorganization, research in neuroscience was divided into two groups, Developmental Neurobiology and Visual Sciences, with staff from the former departments being distributed amongst the two new groups. Richard resumed his role as Head of Developmental Neurobiology again in 1992.

The 1987 review also agreed to build extensions to RSBS to allow staff from Behavioural Biology to be integrated with the rest of the School. These additions were completed in 1989, finally providing modern laboratory facilities and allowing the School to function as originally intended.

From the late 1980s to the mid-1990s, the availability of wallabies from the RSBS colony led to a series of studies on the normal visual pathway and its development, as well as the effect of manipulations such as rearing with a rotational squint (reviewed in [101]). The research repertoire expanded to include studies on somatosensory and auditory function and comparative neuroanatomy of the brain, in addition to motoneuron regulation and development. These new avenues were associated with collaborations with P. Waite (University of New South Wales [UNSW]), one of the authors of this memoir, and K. Ashwell (UNSW), S. Jhaveri and R. Erzurumlu (Massechusetts Institute of Technology), K.‑P. Hoffman and C. Distler (Ruhr- Universität), D. Withington (University of Leeds), and B. Cone-Wesson (University of Southern California, Los Angeles). Richard’s contributions to the study of Australian native mammals were acknowledged in 1991 with the award of the Peter Aitken Medal of the South Australian Museum.

An extensive review of RSBS was undertaken in 1994–1995 by a review committee appointed by the Australian Research Council. In preparation for this review, the School’s submission presented its research under five themes in which Visual Sciences and Developmental Neurobiology were again linked into an integrative neuroscience theme; however, the group structure was maintained. The report of the committee concluded that RSBS was a ‘distinguished, major international centre of outstanding research and teaching in biology’ (RSBS Annual Report 1995). It commented that RSBS provided ‘an excellent environment for graduate and postgraduate training’ and recommended that the mechanism of block-grant funding be continued. The outstanding resource of the wallaby colony that Richard’s vision had initiated was recommended for on- going support as a major focus for developmental research. Whereas research on wallaby visual, somatosensory and auditory function continued to be a major thrust of these studies, new techniques were used. Progress on recording early evoked activity during pouch development was made using current source density analysis. Molecular biological techniques were used to examine gradients of molecules in the developing retina and superior colliculus. Another technique that proved useful was the parallel recording of responses in vivo and in vitro during development, to document the onset of neural activity in the colliculus and cortex.

Richard retired in 1999 but stayed on as Emeritus Professor, continuing with his research collaborations with both students and staff. During Richard’s association with RSBS for over a quarter of a century he produced 69 papers and was associated with 20 postgraduate theses. The marsupial colony was a particularly noteworthy initiative with half of these publications and theses being associated with studies on the wallaby, thus fulfilling one of the original goals for the founding of RSBS. As Professor Jonathan Stone, the current Director of RSBS noted, ‘none of us would doubt that it was Richard’s energy, insight and drive to understand that created this unique project and led to its splendid fruition’.

Scientific work

Nerve regeneration and synaptic mechanisms

Richard’s long-standing interest in synaptic mechanisms began with his early research on spinal reflexes and multiple firing patterns (1, 3). This research was undertaken while a student in Archie McIntyre’s laboratory at the University of Otago in Dunedin, and used to advantage the large superficial fibers of the cat’s dorsolateral tract. Electrophysiological recordings were also used to study cortical responses to afferent inputs (2). This influential study showed the contribution of both group II and III afferents to activity evoked in somatosensory cortex. Richard’s interest in spinal reflexes led to his doctoral thesis on Hoffman reflexes and the maintenance of posture in man. He was able to show that gamma motoneuron activity affected both the dynamic and static sensitivity of muscle spindles (8).

Richard’s understanding of normal impulse patterns and motor control led him to start questioning the effects of neural regeneration and plasticity after injury. It was typical that Richard selected an unusual neurophysiological preparation, the fin of a cichlid fish, taking advantage of its favourable innervation. After crossing the innervation from antagonist muscles, neuromuscular transmission was re-established, but the recovered movements were uncoordinated. This result raised some ‘question about the whole concept of myotopic re-specification of motoneurons and the correlated idea of plastic compensatory changes of spinal cord organization in fish and amphibians’ (10). Richard proposed that differences in recovery between fish and mammals reflected differences in neuromuscular innervation (polyneuronal v. single end-plate) rather than differences in central plasticity of connections between lower and higher vertebrates as suggested by Weiss (1936).

The experiments on fin innervation were followed by a seminal series of publications on fish extra-ocular re-innervation (22, 23, 25, 33, 34). Cutting cranial nerves III and IV resulted in correct eye movements despite misrouted fibres being present and active in both nerves. Since synaptic terminals on the muscles appeared normal, the authors concluded that transmission from inappropriate nerves was suppressed by a competitive molecular recognition between nerve and muscle. This led to the suggestion that similar competitive mechanisms occurring at central synapses and dependent upon activity could be the basis of a learning mechanism, thus linking Richard’s other research interest in learning and memory.

Richard now turned his attention to reassess re-innervation in axolotls (35, 45, 47, 52, 53), the original experimental animal used by Weiss (1936) for his hypothesis on myotopic re-specification. The hind-limb nerve trunks were misdirected and maintained for up to nine months. Movements recovered by three months and were normal, and electrophysiological recordings confirmed that correct innervation was restored. Moreover, the authors confirmed a competitive mechanism favouring the appropriate nerve, by recutting the correct nerve; this resulted in an expansion of territory of the remaining nerve, followed by retraction when the correct nerve regrew. The rapidity with which the expanded innervation appeared (about three days) indicated that widespread misdirected terminals were present, but inactive or suppressed. Cass et al. (35) concluded that the abnormal paths taken by regenerating nerves could have easily led Weiss to the conclusion that functional re-specification of innervation must have occurred, rather than correct re-innervation. Similar experiments on the axolotl shoulder girdle (53) confirmed the competitive mechanisms and showed that suppression of foreign innervation was reversible. Re-establishment of correct innervation depended on a competitive repression of transmission of foreign nerves.

This important body of work on the neuromuscular synapse and the role of competition in re-innervation of muscles was summarized in a major review (62). This highly cited paper discussed regeneration and repression as well as normal developmental mechanisms and the role of motoneuronal death. Motoneuron cell death was one of the first studies undertaken in the new wallaby colony at ANU. Investigation of developmental cell death in both Xenopus (76) and wallaby (77) led to the conclusion that motoneuronal loss was likely to be related to securing specificity of muscle innervation, rather than a mechanism for adjusting motoneuronal population to the size of peripheral musculature.

Interestingly, unlike motor nerves, regenerating sensory nerves showed far less accurate re-innervation to original skin areas. This was especially true for cut, as opposed to crush, nerve injuries with receptive fields often spatially disorganized, discontinuous and overlapping between adjacent fibres after the nerve was cut (47). Cross-innervation experiments of the trigeminal nerve in axolotls (64, 66) showed some components of the reflex response to skin stimulation were appropriate to the new skin area, not just the parent nerve. This provided further evidence to support a role for sensory end-organs in specifying central sensory connections.

Memory formation

The study of memory was one of the big questions that interested Richard. Very little was known of the biological correlates of memory formation in the 1960s when Richard entered the field. His research and thoughts led to the publication of a book in 1974 titled Memory and Nerve Cell Connections (43), and he wrote in its Preface:

The first testing paradigm that Gibbs and Mark used in the studies of memory formation was a one-trial passive-avoidance task in chicks. The chick learned to avoid pecking at an attractive, shiny bead as a result of it being coated with an unpleasantly tasting liquid, methyl anthranilate. The proportion of chicks that did not peck the bead (now not coated with the unpleasant liquid) when it was presented to them some minutes (or hours) later provided a measure of memory retention in the group. The drugs ouabain and ethacrynic acid, which inhibit the sodium–potassium ATPase pump, produced amnesia of the task as long as they were administered to the chicks either just before training with the coated bead or any time up to half an hour after training (27, 30). Hence, they interfered with the early or short-term phase of memory formation. Administration of cycloheximide, an inhibitor of protein synthesis, prevented the formation of long-term memory and did so only after an interval of one hour from training (29). This method of studying memory was used extensively to test different inhibitors of memory formation and it is still used today to investigate both enhancers and inhibitors of memory formation.

Lesley Rogers joined Richard’s laboratory to continue the research on memory formation in 1972 using a new task, one requiring the chick to find food mash scattered on a background of small pebbles that had been stuck to the floor (44). This task revealed the unexpected finding that chicks treated with ouabain were unable to learn to discriminate grain from pebbles in the short-term but some hours later they showed good recall of having learned (55). This task also confirmed that cycloheximide inhibited long-term memory formation and led to the discovery that this drug caused long-lasting impairment of certain aspects of learning (44). Rogers is indebted to Richard for suggesting that she look at the effects of cycloheximide and other memory inhibitors in the left and right hemispheres of the chick separately, since this led to the discovery of lateralization in the chick brain (Rogers and Anson 1979) and opened up a new field of investigation still expanding at the present time.

Richard’s contributions to understanding of the cellular correlates of memory formation were important for two reasons: (i) he formulated clear and testable hypotheses about the cellular events involved, and (ii) he was instrumental in developing methods that could be used to test these hypotheses with ease. His ideas on memory formation are presented clearly in his two books (42, 43), in book chapters (56, 57) and in a report to the Australian Academy of Science (41). Of the book Memory and Nerve Cell Connections one reviewer wrote: ‘…it draws together many strands of evidence that the formation and regeneration of neural connections are highly specific and that, during maturation, these connections can be “enduringly modified” by experience’ (Grinnell 1974). This hypothesis about synaptic competition had also been reported by Richard in an article published in Nature (24). Richard had the ability of writing well for a wide audience. One reviewer of his book commented: ‘[it] will be of interest to all who are concerned in the problem of memory and brain function’ (Pilcher 1975).

Sensory pathway development and central plasticity

Richard’s curiosity about mechanisms of re-innervation in limb and eye musculature soon spilled over into similar questions about central pathways. With his interest in visual learning and memory, it was natural to turn to the visual pathway for investigations of synaptic function and plasticity. Two early studies in 1966 (11, 12) looked at mechanisms of interhemispheric transfer of visual information in fish, in which retinal projections are completely crossed. This was followed in the mid-1970s to early 1980s by a series of studies in goldfish and carp (50, 54, 58, 60, 61, 67) investigating reorganization of retinotectal connections after partial tectal ablations. In collaboration with Lauren Marotte and Judith Wye-Dvorak, anatomical examination and electrophysiological mapping techniques were used to investigate the mechanisms underlying this plasticity. Profuse sprouting was shown to precede reorganization of the whole visual field on to the remaining tectum. Moreover, reorganization was seasonal and dependent on lighting conditions. These environmental effects could be partially modified by thyroxine, indicating a hormonal influence on central plasticity in fish.

With the establishment of the wallaby colony, marsupial sensory function and sensory pathway development became a major focus. The first challenge was to map the normal visual projections to the thalamus, tectum and cortex and to document their developmental time course (79, 81, 86, 87). Topographic precision was shown to be refined during development and was complete prior to eye opening. Access to the pouch young at early ages allowed the use of sensitive, in vivo, anatomical tracing methods that called into question the existence of a waiting period for thalamic afferents in the developing cortex, a central dogma of mammalian cortical development (Shatz and Lushkin 1986). Access to the pouch young also allowed the effects of perturbations such as eye rotation (82) or enucleation (84) to be tested. Eye rotations prior to retinal innervation of the lateral geniculate nucleus (LGN) and the superior colliculus (SC) showed that orderly connections can form in a mammal despite inputs arriving via aberrant pathways, giving clear evidence for specific axon–target interactions. These experiments were followed by more detailed mapping of the ipsilateral and contralateral projections and the effects of eye rotations (92, 93). Powerful techniques of current source density recordings and computer analysis of responses were used to analyse depth profiles of current flow in the developing superior colliculus (94) and later in the visual cortex (111). This provided the first evidence of the location and onset of evoked activity in these visual centres in a mammal in an intact in vivo preparation.

A collaboration with Geoff Henry (John Curtin School of Medical Research) looked at the distribution of different physiological types in the cells that made up the LGN. The aim was to see whether cellular lamination in the LGN was related to functional streaming in the visual pathways to the visual cortex (89). The obvious layering of the LGN in so many species had promoted the idea that it may be a common design feature for separating the functional streams arising from the various classes of retinal ganglion cells. Could it be that the lamination seen in the histological sections of the LGN of macropod marsupials was related to the functional patterns seen in placental mammals? The LGN of the tammar was shown to have an outer alpha segment consisting of six layers and an inner beta segment with three layers. The recordings from single cells indicated that functional streams were not restricted to single layers but that alpha and beta segments, respectively, carried cells with properties similar to the Y and W cells of the cat. Thus the tammar alpha and beta segments resemble the A and C laminae of the cat and possibly also the magnocellular and koniocellular regions of the dorsal LGN of the primate. This broad similarity in functional partition in species with vastly different lifestyles, and separated by 100 million years of divergent evolution, led to the conclusion that it was a general, rather than specific, organizational feature.

As the projects progressed, contributions were made by other workers both from the ANU (Wye-Dvorak, Vidyasagar and Ibbotson) and overseas (Klaus-Peter Hoffmann and Caudia Distler, Ruhr Universität, Bochum). Experiments in primary visual cortex aimed to measure the cortical magnification factors across the visual field to compare them with the retinal ganglion cell densities (91). Significantly, the two areal graphs matched one another in the vertical meridian but the cortical magnification failed to follow the high retinal cell densities found horizontally along the visual streak. Thus, although ganglion cell density would indicate a high level of pattern recognition in the peripheral streak, this was not confirmed by a matching elevation in cortical magnification. There is therefore an unexplained annulment of a retinal design feature. This could lead to a loss of resolution, perhaps to favour the early detection of the movement of approaching predators. Further work on the cortex (91, 116) showed that the wallaby has a highly evolved primary visual cortex (area V1), with response properties similar to those in cats and primates. Moreover, anatomical work showed that V1 received most input from the area of the retina that looks directly forwards, thus allowing wallabies to resolve images with the highest quality in the location where it most needs the information (109).

Both anatomical and physiological experiments were used to study response properties of cells in the nucleus of the optic tract (NOT), and the effects of early eye rotation (97, 99, 102, 105, 107). NOT is a brain region specialized for detecting the motion of large areas of the visual field caused by self-motion (i.e. head rotation) and it drives optokinetic eye movements that stabilize the retinal image. Investigations showed for the first time in any mammalian species that the NOT contained two distinct cell types, a finding that has now been repeated in other species (Wiley and Crowder, 2000). Response properties indicated that a motion detector, the Reichardt detector, was in operation in the wallaby optokinetic system. Rotation of the eyes at birth did not lead to any environmentally influenced change in the preferred directions of NOT neurons, showing that the system is hard-wired (99). There was no evidence of any reorientation of motion sensitivity in the rotated eye to bring it into line with the induced cyclical squint.

Other studies investigated binocular interactions in the NOT (114), how the neurons adapt during motion stimulation (105), and several other biophysical properties of the cells (107). A major discovery was that neurons close to the NOT coded information related to saccadic eye movements, a little-known phenomenon in mammals (96).

Besides these anatomical and physiological approaches, molecular biology was used to examine the potential receptors and ligands involved in recognition of retinal axons with their target cells in the SC. Studies in the chick had reported that Eph receptor tyrosine kinases and their ligands (the ephrins) were critical components in the development of topography in the tectum. In collaboration with Maria Vidovic and Lauren Marotte, the wallaby retina and SC were shown to express both the EphA receptors and their ephrins in the adult and during development. Moreover there was differential expression of receptor in the retina and ligand in the SC (108), indicating that these signalling molecules may have a role in the development of topography in mammals.

Finally, Richard introduced behavioural studies on wallaby visual acuity, contrast sensitivity and spectral sensitivity. Combined with retinal morphology this approach showed that wallabies have dichromatic vision, with pigments similar to those in many placental mammals (104, 110).

The early 1990s saw the extension of research in the visual pathway to include other sensory systems. In collaboration with P. Waite (UNSW) and L. Marotte (ANU) the somatosensory pathway from the whiskers was investigated (88). In rodents the whisker pathway has proved valuable for studies in development and plasticity, with each whisker represented in visible and quantifiable aggregations of cells (barrels) within the somatosensory cortex (reviewed in Waite and Ashwell 2004). It was found that wallabies also had whisker-related aggregations in the cortex. These aggregations were shown to develop about three months after birth in wallabies, allowing questions about factors controlling timing of development (106) and onset of functional activity (108) to be explored.

Other sensory systems investigated were olfaction (83) and audition (95, 100, 112, 113), the latter in association with A. Gummer, K. Hill and others. Auditory- evoked potentials were used to show when responses could first be detected in the pouch young of wallabies and to follow their changes as hearing developed. It was also found that the cochlear nerve showed spontaneous activity prior to any evoked responses being present, raising the possibility that such spontaneous firing may be important in shaping development of connections from the two ears. In the adult superior colliculus, auditory responses were present in deeper layers, as in other species.

Fruitful collaborations developed between Richard’s group and the Division of Wildlife Research, CSIRO. Although Richard was not a co-author, he contributed to work on reproduction and development, especially in the area of reproductive responses of female tammar wallabies to photoperiod. This resulted in a detailed understanding of the role of the pineal gland in transducing information about day length into hormonal response in the anterior pituitary gland and thence to the ovary and dormant embryo (reviewed Tyndale- Biscoe et al. 1986). The most remarkable finding was the rapidity of response of female tammars to a change in day length maintained for only three successive days. In an attempt to locate the centre in the brain that responds so rapidly, a collaborative programme was begun between the two groups and pursued intermittently over a decade.

One outcome of the collaboration between a visiting scientist at CSIRO, Shinji Hayashi, and Brian Wimborne and Richard at RSBS was the preparation of an atlas of the brain of the tammar wallaby. While an atlas of the brain of the South American opossum, Didelphis marsupialis, had been published many years before (Oswaldo-Cruz and Rocha-Miranda 1968), the tammar belongs to a different order of marsupials (Diprotodontia), which possess the fasciculus aberrans, an interhemispheric commissure not found in any other group of mammals. Many features of their brain structure show closer similarities to eutherian mammals, primates and non- primate carnivores than does the opossum.

Contribution to professional societies

Australian Neuroscience Society

Richard served as President of the ANS for 1998–1999, and as its President Elect and Past President for the period immediately preceding and succeeding this. After several years of informal meetings throughout the 1970s, ANS was formally constituted in 1981 to promote and foster all branches of neuroscience (Redman 1992). It has grown dramatically over the past 25 years to be the premier society for representing and supporting neuroscience in the Australasian region.

Richard’s presidency was associated with continued growth of the membership of the society and successful annual meetings. Richard was keen to ensure widespread representation of members in Society governance and strengthened the process of nomination to Council. Close to Richard’s heart was the concern to promote Australian neuroscience better, to both government and the wider community. He attended the FASTS National Forum ‘Australian needs, Australian research’ in July 1999 convened to discuss the government’s Green Paper on research funding. Richard and the ANU state representative on ANS, John Bekkers, wrote a report on this (ANS Newsletter October 1999) that was also presented on The Science Show, broadcast by the Australian Broadcasting Corporation. Richard recognised the value of media coverage in promoting neuroscience research and developed guidelines for meeting organizers on how best to alert journalists about upcoming ANS meetings and what information to include.

Richard’s commitment to multidisciplinary studies, so evident in his own research, was also apparent in his activities as ANS President. He initiated and co- ordinated a symposium, ‘Neurology for the Neuroscientists’, as a joint venture between ANS and the Australian Association of Neurologists. The aim was to provide a forum for interaction and discussion between neurologists and basic scientists, with the clinicians presenting problems that they encountered in practice. This innovative meeting was successful, with fruitful discussion between attendees and the possibility of productive collaborations.

Other interests

Richard was close to his two children and his grandchildren, Lily (born 17 March 2003) and Jacob (born 31 May 1995).

Richard’s talents extended beyond scientific writing into creative writing of poetry and also into music. He so moulded these broad talents together that he was often described as a Renaissance man. Richard was open to ideas and his view of the world was far-reaching. As well as science, music and poetry, Richard shared a great love of sailing. He played the violin well and, in his later years, developed his passion for writing poetry. In 2000 a collection of his poetry, entitled Sting in the Tail, was published by Ginninderra Press (ACT, Australia).

His violin playing began when he was in primary school and the enthusiasm and skill lasted throughout his life. His summer holidays were, for many years, spent at New Zealand’s summer music school at Cambridge, near Hamilton.

Richard Mark playing the violin, 22 March 1974, at a party to farewell Professor Manfred Zimmerman, who had been visiting the Physiology Department at Monash University on his sabbatical leave. [Photographer: Diana Dorrington (née Harrison)]

Richard had a life-long interest in boats and sailing. Tauranga, where Richard grew up, is a coastal town on a beautiful sheltered harbour in the Bay of Plenty, and it was here that Richard’s passion for the sea and his love of sailing began. For many years the young Richard shared a small sailing boat with his cousins and spent as much time as possible on this boat sailing in the Tauranga Harbour, or as a deck hand on the coastal boats that sailed and worked along the coast. While in Canberra, he owned an ocean-going wooden boat that he sailed as often as possible off the New South Wales south coast.

Sailing was more that just a pleasant pastime to Richard – it was an integral part of his love and experience of the sea in its many and ever-changing moods. Over the whole range of his sailing experiences, he often found moments of sheer beauty and a profound sense of communion with the fundamentals of nature. Besides his own love of sailing and the ocean, he made a sizeable contribution to boating at Bateman’s Bay, especially during his long term as chairman of the Marina Co-operative. His hard work and effective leadership over many years were vital to boat owners, eventually securing a greatly improved marina facility and the construction of a first-class slipway and hardstand area.

Conclusions

‘What have you discovered today?’ was one of Richard’s special phrases, said quite gently as he waited anxiously to hear. It was his way of sharing the excitement of being at the forefront of his field.

His generosity and enthusiasm is evidenced by the large number of people with whom he worked and published. They came from all over the world, attracted by Richard’s intellectual leadership and the scientific opportunities his laboratory provided, such as the unique resources of the marsupial colony. Richard particularly enjoyed interacting with his many research students and was an exceptional supervisor, committed and supportive but never dominating. Students and colleagues of Richard formed firm friendships and have remained together as friends and collaborators for years after their time in his laboratory. This speaks of an unusually positive and non-competitive laboratory culture, generated by Richard. His students and colleagues respected his honesty in science and in life and say that they learnt more from him than science.

Richard’s scientific vision was broad and far-reaching. It encompassed a wide range of ‘big’ questions, many different experimental approaches and a large variety of vertebrate species. His vision in proposing establishment of the wallaby colony nearly thirty years ago has provided Australia with an unparalleled resource for studying mammalian neural development, the potential of which is still being realised today. His leadership in bringing a multidisciplinary approach to neuroscience, in teaching as well as in research, was enlightened and progressive and ensured that the discipline was provided with well- trained young researchers.

He was an excellent guide for so many of us – and his legacy to Australian neuroscience will live on not only in those who knew and worked with him but also in those who study his publications.

Acknowledgments

In writing this memoir, the authors have appreciated contributions from many sources. Dr Lauren Marotte deserves particular mention for her support and encouragement. We gratefully acknowledge contributions from family, friends and colleagues: Gerda Mark, David Mark, Sally Barnett, Dick Cornish, Diana Dorrington, Professors Michael Gazzaniga, Jacques Paillard, Uwe Proske and Hugh Tyndale- Biscoe, and Drs Dick Barnett, Marie Gibbs, Geoff Henry, Michael Ibbotson, Ray Johnstone and Cathy Leamey. We would also like to acknowledge photographers Jeff Wilson, for the formal portrait taken at the ANU, and Diana Dorrington (née Harrison), for the pictures taken at Monash University.

References

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Bibliography

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46. DAVEY D.F., MARK R.F. (1975) Structure and innervation of extraocular muscles of Carassius. J. Anat. 120, 131–147.

47. JOHNSTON B.T., SCHRAMECK J.E., MARK R.F. (1975) Re-innervation of axolotl limbs. II. Sensory nerves. Proc. Royal Soc. Lond. (B) 190, 59–75.

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64. GRIERSMITH B.T., MARK R.F. (1981) Behavioral and electrophysiological study of cutaneous trigeminal nerves in axolotls. I. Normal innervation and reinnervation following nerve section. Dev. Brain Res. 2, 271–285.

65. SANBERG P.R., FAULKS I.J., BELLINGHAM W.P., MARK R.F. (1981) Relationship between tonic immobility and operant conditioning in chickens Gallus gallus. Bird Behav. 3, 51–56.

66. GRIERSMITH B.T., MARK R.F. (1981) Behavioral and electrophysiological study of cutaneous trigeminal nerves in axolotls. II. The effects of cross-anastomosis of nerves. Dev. Brain Res. 2, 287–301.

67. MAROTTE L.R., MARK R.F., WYE‑DVORAK J. (1981) Retinotectal reorganization in goldfish – III. Effect of thyroxine. Neuroscience 6, 1591–1600.

68. SANBERG P.R., FIBIGER H.C., MARK R.F. (1981) Body weight and dietary factors in Huntington’s disease patients compared with matched controls. Med. J. Aust. 1, 407–409.

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74. ENRLICH D., MARK R.F. (1984). An atlas of the primary visual projections in the brain of the young chick (Gallus gallus). J. Comp. Neurol. 223, 592–610.

75. ENRLICH D., MARK R.F. (1984). Retinal topography of primary visual centres in the brain of the chick (Gallus gallus). J. Comp. Neurol. 223, 611–625.

76. DENTON C.J., LAMB A.H., WILSON P., MARK R.F. (1985) Innervation pattern of muscles of one-legged Xenopus laevis supplied by motoneurons from both sides of the spinal cord. Dev. Brain Res. 17, 85–94.

77. COMANS P.E., MCLENNAN I.S., MARK R.F. (1987) Mammalian motoneuron cell death: development of the lateral motor column of a wallaby (Macropus eugenii). J. Comp. Neurol. 260, 627–634.

78. MAROTTE L.R., MARK R.F. (1987) Retinotectal reorganization in goldfish – IV. Effects of retinal ganglion cells after half tectal ablation. Neuroscience 3, 745–754.

79. WYE-DVORAK J., LEVICK W.R., MARK R.F. (1987) Retinotopic organization in the dorsal lateral geniculate nucleus of the tammar wallaby (Macropus eugenii). J. Comp. Neurol. 263, 198–213.

80. COMANS P.E., MCLENNAN I.S., MARK R.F., HENDRY I.A. (1988) Mammalian motoneuron development: effect of peripheral deprivation on motoneuron numbers in a marsupial. J. Comp. Neurol. 270, 111–120.

81. FLETT D.L., MAROTTE L.R., MARK R.F. (1988) Retinal projections to the superior colliculus and dorsal lateral geniculate nucleus in the tammar wallaby (Macropus eugenii): I. Normal topography. J. Comp. Neurol. 271, 257–273.

82. MAROTTE L.R., MARK R.F. (1988) Retinal projections to the superior colliculus and dorsal lateral geniculate nucleus in the tammar wallaby (Macropus eugenii): II. Topography after rotation of an eye prior to retinal innervation of the brain. J. Comp. Neurol. 271, 274–292.

83. ELLENDORFF F., TYNDALE-BISCOE C.H., MARK R.F. (1989). Ontogenetic changes in olfactory bulb neural activities of pouched young tammar wallabies. In The Endocrine Contact of the Fetus. (Ed. W. Kunzel and Z. Jensen.) Springer-Verlag, Berlin. pp. 193–200.

84. MAROTTE L.R., FLETT D.L., MARK R.F. (1989) Effects of very early monocular and binocular enucleation on primary visual centers in the tammar wallaby (Macropus eugenii). J. Comp. Neurol. 282, 535–554.

85. GREGORY J.E., MARK R.F., MORGAN D.L., PATAK A., POLUS B., PROSKE U. (1990) Effects of muscle history on the stretch reflex in cat and man. J. Physiol. 424, 93–107.

86. SHENG X.M., MAROTTE L.R., MARK R.F. (1990) Development of connections to and from the visual cortex in the wallaby (Macropus eugenii). J. Comp. Neurol. 300, 196–210.

87. SHENG X.M., MAROTTE L.R., MARK R.F. (1991) Development of the laminar distribution of thalamocortical axons and corticothalamic cell bodies in the visual cortex of the wallaby. J. Comp. Neurol. 307, 17–38.

88. WAITE P.M.E., MAROTTE L.R., MARK R.F. (1991) Development of whisker representation in the cortex of the tammar wallaby Macropus eugenii. Dev. Brain Res. 58, 35–41.

89. HENRY G.H., MARK R.F. (1992) Partition of function in the morphological subdivisions of the lateral geniculate nucleus of the tammar wallaby (Macropus eugenii). Brain Behav. Evol. 39, 358–370.

90. MARK R.F., MAROTTE L.R. (1992) Australian marsupials as models for the developing mammalian visual system. Trends Neurosci. 15, 51–57.

91. VIDYASAGAR T.R., WYE-DVORAK J., HENRY G.H., MARK R.F. (1992) Cytoarchitecture and visual field representation in area 17 of the tammar wallaby (Macropus eugenii). J. Comp. Neurol. 325, 291–300.

92. MARK R.F., JAMES A.C., SHENG X.M. (1993) Geometry of the representation of the visual field on the superior colliculus of the wallaby (Macropus eugenii). I. Normal projection. J. Comp. Neurol. 330, 303–314.

93. JAMES A.C., MARK R.F., SHENG X.M. (1993) Geometry of the projection of the visual field onto the superior colliculus of the wallaby (Macropus eugenii). II. Stability of the projection after prolonged rearing with rotational squint. J. Comp. Neurol. 330, 315–323.

94. MARK R.F., FREEMAN T.C., DING Y., MAROTTE L.R. (1993) Two stages in the development of a mammalian retinocollicular projection. Neuroreport 5, 117–120.

95. GUMMER A.W., MARK R.F. (1993) Patterned neural activity in brain stem auditory areas of a prehearing mammal, the tammar wallaby (Macropus eugenii). Neuroreport 5, 685–688.

96. IBBOTSON M.R., MARK R.F. (1994) Wide- field nondirectional visual units in the pretectum: do they suppress ocular following of saccade-induced visual stimulation. J. Neurophysiol. 72, 1448–1450. Corrigendum in J. Neurophysiol. 72(4), i.

97. IBBOTSON M.R., MARK R.F., MADDESS T.L. (1994) Spatiotemporal response properties of direction-selective neurons in the nucleus of the optic tract and dorsal terminal nucleus of the wallaby, Macropus eugenii. J. Neurophysiol. 72, 2927–2943.

98. SANBERG P.R., JOHNSON T.W., CAHILL D.W., MARK R.F. (1994) Avian telencephalon and body weight. Physiol. Behav. 55, 1109–1112.

99. HOFFMAN K.P., DISTLER C., MARK R.F., MAROTTE L.R., HENRY G.H., IBBOTSON M.R. (1995) Neural and behavioral effects of early eye rotation on the optokinetic system in the wallaby, Macropus eugenii. J. Neurophysiol. 73, 727–735.

100. WITHINGTON D.J., MARK R.F., THORNTON S.K., LIU G.B., HILL K.G. (1995) Neural responses to free-field auditory stimulation in the superior colliculus of the wallaby (Macropus eugenii). Exp. Brain Res. 105, 233–240.

101. MARK R.F. (1996). Tyndale-Biscoe and the developmental neurobiology of marsupial vision at the Australian National University. In Marsupial Biology: Recent Research, New Perspectives. (Ed. N.R. Saunders and L.A. Hinds.) UNSW Press, Sydney. pp. 311–326.

102. IBBOTSON M.R., MARK R.F. (1996) Impulse responses distinguish two classes of directional motion-sensitive neurons in the nucleus of the optic tract. J. Neurophysiol. 75, 996–1007.

103. FREEMAN T.C., JAMES A.C., MARK R.F. (1997) Conduction and synaptic transmission in the optic nerve and the superior colliculus during development of the retinocollicular projection in the wallaby (Macropus eugenii). J. Comp. Neurol. 380, 472–484.

104. HEMMI J.M., MARK R.F. (1998) Visual acuity, contrast sensitivity and retinal magnification in a marsupial, the tammar wallaby (Macropus eugenii). J. Comp. Physiol. [A] 183, 379–387.

105. IBBOTSON M.R., CLIFFORD C.W., MARK R.F. (1998) Adaptation to visual motion in directional neurons of the nucleus of the optic tract. J. Neurophysiol. 79, 1481–1493.

106. WAITE P.M.E, MAROTTE L.R., LEAMEY C.A., MARK R.F. (1998) Development of whisker-related patterns in marsupials: factors controlling timing. Trends Neurosci. 21, 265–269.

107. IBBOTSON M.R., CLIFFORD C.W., MARK R.F. (1999) A quadratic nonlinearity underlies direction selectivity in the nucleus of the optic tract. Vis. Neurosci. 16, 991–1000.

108. VIDOVIC M., MAROTTE L.R., MARK R.F. (1999) Marsupial retinocollicular system shows differential expression of messenger RNA encoding EphA receptors and their ligands during development. J. Neurosci. Res. 57, 244–254.

109. WIMBORNE B.M., MARK R.F., IBBOTSON M.R. (1999) Distribution of retinogeniculate cells in the tammar wallaby in relation to decussation at the optic chiasm. J. Comp. Neurol. 405, 128–140.

110. HEMMI J.M., MADDESS T., MARK R.F. (2000) Spectral sensitivity of photoreceptors in an Australian marsupial, the tammar wallaby (Macropus eugenii). Vision. Res. 40, 591–599.

111. PEARCE A.R., JAMES A.C., MARK R.F. (2000) Development of functional connections between thalamic fibres and the visual cortex of the wallaby revealed by current source density analysis in vivo. J. Comp. Neurol. 418, 441–456.

112. LIU G.B., HILL K.G., MARK R.F. (2001) Temporal relationship between the auditory brainstem response and focal responses of auditory nerve root and cochlear nucleus during development in the tammar wallaby (Macropus eugenii). Audiol. Neurootol. 6, 140–153.

113. LIU G.B., MARK R.F. (2001) Functional development of the inferior colliculus (IC) and its relationship with the auditory brainstem response (ABR) in the tammar wallaby (Macropus eugenii). Hearing Res. 157, 112–123.

114. IBBOTSON M.R., MAROTTE L.R., MARK R.F. (2002) Investigations into the source of binocular input to the nucleus of the optic tract in an Australian marsupial, the wallaby Macropus eugenii. Exp. Brain Res. 147, 80–88.

115. MARK R.F., FLETT D.L., MAROTTE L.R., WAITE P.M.E. (2002) Developmental onset of functional activity in the wallaby whisker cortex in response to stimulation of the infraorbital nerve. Somatosens. Mot. Res. 19, 198–206.

116. IBBOTSON M.R., MARK R.F. (2003) Orientation and spatiotemporal tuning of cells in the primary visual cortex of an Australian marsupial, the wallaby Macropus eugenii. J. Comp. Physiol. A Neuroethol. Sens. Neural Behav. Physiol. 189, 115–123.

L.J. Rogers, Centre for Neuroscience and Animal Behaviour, University of New England, Armidale, Australia.