William Iñaki Alan Haynes

312 Pages·2015·24.48 MB·French

by  William I. Haynes

Université Pierre et Marie Curie
Ecole Doctorale 158: Cerveau Cognition Comportement

WHEN ANATOMY DRIVES PHYSIOLOGY:
EXPANDING THE ACTOR-CRITIC MODEL OF THE BASAL GANGLIA TO NEW SUB-
THALAMUS CONNECTIONS

Doctoral thesis presented by
William Iñaki Alan Haynes

To obtain the title of Doctor in Neuroscience from the Université Pierre et Marie Curie

Defended on the 8th September 2014
In front of the following Jury

Luc Mallet, M.D., Ph.D. Directeur
Suzanne N. Haber, Ph.D. Directeur
Christelle Baunez, Ph.D. Rapporteur
Olivier David, Ph.D. Rapporteur
Philippe Faure, Ph.D.
Carine Karachi, M.D., Ph.D.
Stéphane Palfi, M.D.
Pierre Pollak, M.D., Ph.D.

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PREFACE

It is with pleasure tinged with a bit of frustration that I write down the last words of this
thesis. While I am glad to have reached the end of this journey and proud of the work I have
done, there is still much left to do and I feel as if I had enough material for a second thesis.
But this shall have to wait. My first thanks go to my jury, Drs Baunez and David, my
rapporteurs, Drs Faure and Karachi, and the Profs Palfi and Pollak. While this thesis will
probably not be the ideal light reading for the summer, I hope that it will be interesting to you
nevertheless.
I wandered into science a bit by happenstance. After the end of the first year of medical
school, wanting to keep my options open, I applied to the MD-PhD program of the Université
Paris Descartes. I have to thank Prof. Chottard, Prof. Chelly and Prof Ascher for this
opportunity as well as the wonderful Mylène Bisson who’s maternal love and bossyness have
been a key to this program’s success. Prof Ascher will note how, ironically, I am the only one
to have pushed the door to neuroscience. In the same line, I need to thank Jehanne, a
classmate at that time, for sending me, unknowingly, to Luc’s lab. For a reason now obscure I
wanted to study the effects of morphine on depression, but she had already applied to the said
lab. So, browsing through the list of teams, I came across this one group that stuck electrodes
in human brains and thought ‘that looks cool’.
I still remember my first meeting with Luc, Jérôme and Marie-Laure and how I was adamant
about never doing electrophysiology and would prefer to try my hand at functional MRI. Five
years later, I am extremely happy of my choice despite never doing functional MRI. Luc, these
have been great years. I am especially grateful of you pushing me out of my comfort zone and
challenging my various ideas, hypotheses and wild thoughts, forcing me to build rationally
what I guessed at intuitively. If things might have been rocky at some points in my progression
through what my friends Ben and Sarah call the ‘five stages of the PhD student’, I hope we
will continue to be such good friends. I still do not think that I will become a psychiatrist but
you have another three years to convince me otherwise.
Jérôme, thank you for your anatomical support in this team of functionalists. While we always
had a quiet relationship, your advice was precious and our musical discussions a welcome
distraction. I do not despair of one day seeing those Golgi cases for myself. Marie-Laure, it is
you I have to thank for introducing me to the world of DBS, SUA and LFP and other
acronymns. I would not have survived my first years without your clinical and experimental
insight.
We had to rotations in our MD-PhD program. While I enjoyed my only summer so far in
Paris for the first one, I wanted to try somewhere new for the second. Dear Suzanne, I believe
you might have been my toughest boss so far but I am glad to have learned an anatomist’s
rigor. This does not mean I had a bad time in Rochester. On the contrary, I very much
enjoyed my time there whether charting fibres in an OCD fashion or having dinner in your
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backyard. Admittedly, I will make sure that any future visit will take place during the summer.
At this point, I also need to thank the French Fulbright commission for awarding me the grant
that has covered my last nine months in Rochester.
During these five years I was also blessed with two wonderful teams without whom I would
not have survived. Margot, I am sorry never to have developed checking symptoms to
integrate your cohort. Maybe our psychotherapy sessions by the coffee machine are to blame
for this setback. Anne-Hélène you have been a great friend and support all along even though
you had already left the lab. You gave me an outlet knowing both what I was going through
and where I am headed. Christian, you’re worse than the peskiest of little brothers. Thanks
for taking the time to poke me in the ribs at least once a day. Aure-Elise, teaching you was a
pleasure and made me learn just as much as my own work. I wish you luck wherever you are
going. Karim, despite my occasional whining, your technical help has been invaluable and I
hope we will continue to work together. We did not have much time to talk Eric, but
congratulations for your new position and might your mice prove as wonderful as you would
like them to be. Marine, I promise you that you will survive MatLab.
Sarah, working alongside you was great fun even if we drove the others nuts during the
journal clubs. I am going to miss those epic arguments. I hope you will too. I am also
indebted to you and Ben for your precious help in managing my last minute analyses before
SfN this year. Eun-Young, you will now be able to invade that middle table after months
hardly thought. Thanks for making fun of me and helping me unwind. If ever you come to
Australia I’ll make sure to take you to a baaa. Julia, your technical mentoring was and is still
invaluable. My only regret is to not have joined in the mud run. Anna and Lisa, thank you for
saving me, respectively, from my clumsiness in the wet lab and from the UofR administration.
As for you Ziad, you are now the only male left in our lab outside of the occasional monkey.
Forgive me for abandoning you to Sarah and Eun-Young’s full attention.
The multiple methods used in my thesis meant that I was also dependent on a number of
people outside my team. Thus, I wish to thank the Dr Karachi once again, this time for
opening us the doors to her operating room, as well as the rest of the neurosurgical staff for
being always smiling and helpful. I am also extremely grateful to the patients of preSTOC2
and METATOC for not only participating but also been as involved as they were in our
experiments. In this context, I was also dependent on Antoine Ducorps and Christophe Gitton
smiling help and good will to access the MEG scanner at sometimes very short notice. Thank
you also Sara for giving me my first MatLab crash-course and setting me up for my MRI
analyses, and Alexandre Vignaud for your experience in structural MRI.
If my PhD years were so great it is also that I was surrounded by wonderful people outside
the lab. Jack, Jim and Rebecca, thank you for being such good friends in Rochester, picking
me up from the airport so often and making sure I experienced the real Halloween and
Thanksgiving. I hope I will be able to return the favour one day. Morgane, I met you at the
ICM yet we saw each other most often upstate NY. Your French touch and presents of foie
gras were most appreciated. Together, we also founded the Ajités which was an enriching
experience. Through them, I met Kristen, Jean, Pinar, Alexandra, Patricia, Morwena and all
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the others who were always ready for a coffee break or a drink after work. Organising the
association was hard work but I hope you can continue doing such a good job.
Mathilda, Elinor and my dear parents, thank you for being so supportive and giving so much
of your time in the final stages of this thesis. Your confidence in me has always been a boost.
Finally, dearest Christoph, thank you for sticking with me half a planet away and visiting me
so often. Thank you for bearing with me during these last two months here yet not there. I
never expected as much and it meant the world to me.

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