News & Media

March 2004
Director's Corner: The Pocket Watch Synapse

"Thought is only a flash between two long nights, but this flash is everything…" Henri Poincaré Poetic, but true in some sense. In our brains, the "flash" occurs an uncountable number of times a second, across trillions of tiny synapses. The synapse has been termed a "molecular machine" (what a remarkable product of Nature's nanotechnology program!). It is the contact point between nerve cells, and it is the fundamental unit by which the circuitry in the brain is set up during development. In last month's Director's Corner, I pointed out that we now have an extensive catalogue of the major component proteins that go into forming synapses in the central nervous system. We will continue to expand this catalogue, but even now we can begin the difficult task that lies ahead - studying how these proteins become concentrated within very small regions of the surface of the nerve cell to make a synapse, and which proteins associate closely with each other to make each synapse work. In time, we hope to understand how synapses change as our brains learn and make new memories. Ultimately, we want to know how normal synaptic function becomes compromised in neurological diseases. As we make progress, we will develop new therapeutic approaches to restore the function of defective synapses.

In beginning to explore this new frontier - and we are just at the very beginning - the "molecular machine" analogy is a good starting point. How are synapses made in the first place?

Imagine that each miniscule synapse is put together like a "simple" machine - say, an old style mechanical pocket watch*. Each component synaptic protein may be thought of as a separate cog in the watch. In this pocket watch, there are hundreds of cogs, of different sizes and shapes. Each cog must be "coupled" to other specific cogs, and there is a correct order by which each must be engaged with its neighbours during manufacture. The whole business, when correctly assembled, must work perfectly - and each cog must interact with the others synchronously, smoothly and with complete accuracy.

Now, just having the "cog catalogue" tells us nothing about how our synaptic pocket watch is assembled in the first place, or how it works when completed. At this moment, the synaptic protein cogs lie in a jumble on my desk, and as yet we have only incomplete design plans to work with to put the cogs in the proper relationship with each other and to assemble them correctly. One thing is certain - we cannot readily predict the "correct" way Nature organizes them but this organization is absolutely critical; practically speaking, no matter how many times I throw all the cogs into the air - they will not fall to my desk as a perfectly assembled “pocket watch” synapse.....

So this is the task we face - to painstakingly analyze our list of component molecular cogs, and experimentally determine how they fit together to form the marvelous molecular machine that is the synapse.

* Incidentally, the pocket watch has been used as an intriguing model in other important problems in biology - see, for example "The Blind Watchmaker" by Richard Dawkins, and "Darwin's Dangerous Idea" by Daniel Dennett.

Please send any comments about the Director's Corner to david.colman@mcgill.ca

Faculty Recruitment Leslie Fellows, MD, PhD, currently at the University of Pennsylvania, will join the MNI faculty on July 1 as an assistant professor. Dr. Fellows, who works on cognition and frontal lobe function, received her medical training at McGill and completed her PhD at Oxford University. Dr. Michael Sinnreich will join the faculty at the MNI as a Physician Scientist in April 2004. Dr. Sinnreich is a trained neurologist and has a PhD in neuroscience. His clinical and research activities will focus on the neuromuscular field.

New Advisory Board Members Mr. Patrick Cheung of Montreal recently agreed to join the MNI Advisory Board. Mr. Cheung brings enthusiasm and expertise from his career in the financial sector and his close ties with China and Singapore. Mr. Najeeb Khalid, also of Montreal, has agreed to serve on the MNI Advisory Board. Mr. Khalid, a native of Pakistan, is a high tech entrepreneur and has founded a number of companies, including Escher-Grad, the company he currently heads.  We are honoured with the commitment of our new board members and appreciate this new friendship with the Neuro.

Coming Events Leon Wolfe Symposium Please join us in welcoming Professor Jeanne Wolfe, Professor of Urban Planning, McGill, and other family members to the day long Leon Wolfe Symposium, Thursday, March 25, 2004, de Grandpré Communications Centre (program). Scientists from Canada, Switzerland and the US will speak and the inaugural Leon Wolfe Killam Lecture will be delivered at 4 pm by Dr. Nicholas Bazan from Louisiana State University Neuroscience Center of Excellence. Remembering Dr. Wolfe’s work as a neurochemist, Dr. William Feindel wrote: “As you know, our brains are stuffed with hundreds of chemicals. Some are simple – like water – which makes up an embarrassing 80% by weight of our brain, or glucose and oxygen, which supply most of the energy for our thinking. Cut these off for a few minutes and our brains go blank. But Leon’s work with his research team dealt with the most complex of brain compounds – esoteric substances such as gangliosides, prostaglandins, leukotrienes, thromboxanes, lipofuscins, dolichols, and eicosanoids. Working with his colleagues in neurology, genetics and pathology, he became a master detective in unravelling the relationships of these arcane chemical factors in a number of eponymic neurological disorders such as Kuf’s syndrome, Batten’s disease, and the syndromes of Tay-Sachs, Hermansky-Padlack, Fabry and Krabbe.” (Neuroimage, Nov 2002) Dr. Hanna Pappius wrote of her colleague: “Life in his orbit was never dull and was a privilege.”

ALS Benefit Amyotrophic Lateral Sclerosis (ALS) research at the MNI will benefit from funds raised by the Montreal Lions Club at their 80th anniversary Gala Dinner Dance to be held on Saturday, March 20. Tickets for the formal event at Buffet Roma (8050 Chamilly, Saint Leonard) are $85 per person with cocktails at 6:00 pm, dinner and dancing to follow. For reservations or more information contact: Maria Menger, 514-254-0723, maria_menger@can.salvationarmy.org or Annibale, 450-662-6975.

Brain Awareness Week Neuroscience graduate students have once again organized activities for Brain Awareness Week, March 15-18, 2004. To celebrate this annual event, marked across North America, students will present programs at local schools and have planned a series of public lectures. This is a great opportunity to introduce your friends to the field of neuroscience. A complete list of activities is posted at http://www.sfn-montreal.ca/BAW/.

Neuro at Night “Stroke – Latest findings on preventing and coping” is the topic of the next Neuro at Night, Tuesday, April 13 at 7:30 pm in the Jeanne Timmins Amphitheatre. Dr. Robert Côté and Dr. Nancy Mayo will speak at this free, public lecture.

Speakers Calendar For a complete list of Seminars, Lectures and Rounds please check the MNI Calendar.

Recent visitors The MNI was privileged to host Mrs. Jeanine Yamamoto, her daughter, Anne Marie, and granddaughters Hilary and Meredith at the symposium honouring the memory of her husband, Dr. Lucas Yamamoto. Dr. Yamamoto, trained as a neurosurgeon, worked as a radiochemist for over 30 years at the MNI. His commitment to training Japanese scientists and to treating patients in the Japanese community in Montreal was recognized by his former colleagues, including Dr. Hideaki Nukui, Dean, Faculty of Medicine Yamanashi University (former student) and Mr. Tetsuo Shioguchi, Consul General of Japan.  At the symposium, Dr. Nukui presented a gift of $20,000 from the Japanese fellows of the MNI to the Neuro library in honour of Dr. Yamamoto.

Dr. Arthur Porter, newly named CEO of the MUHC, met with David Colman. Dr. Porter previously visited and toured the MNH.

In the News Dr. Doug Arnold’s group reported widespread nerve fibre damage in brains of patients with multiple sclerosis (MS) associated with fatigue. These findings, published in February issue of The Archives of Neurology, suggest that diffuse white matter disease translates into an increase in the central nervous system effort required by a patient with MS to perform the same activity as compared with a disease-free subject. (press release)

Dr. Amit Bar-Or’s work, appearing in this month’s Journal of Immunology will receive attention in the “Highlights” section of Nature Reviews Immunology. His research describes a fundamental mechanism by which normal human B cells may regulate immune responses. These responses could be relevant to diseases such as multiple sclerosis.

Dr. Peter McPherson's group reported, in the March 16th issue of the Proceedings of the National Academy of Sciences of the USA, the most complete picture to date of the components of the molecular machinery that controls the entry of nutrients and other molecules into cells. Dr. McPherson and colleagues used a proteomics approach to identify 209 proteins of clathrin-coated vesicles.

These vesicles are the vehicles by which cells are able to take up nutrients, such as cholesterol, from their environment. Defects in this uptake process have profound repercussions on cellular function and human health. (press release) Congratulations to Dr. Antonio Strafella who received a CFI New Opportunities Grant.