With the recent discoveries of phenomena such as plateau potentials, bistability, and synaptic amplification the focus of motoneuron research has been directed to the dendritic processes giving rise to these latent behaviors. The common consensus is that the mechanism behind bistability (an L-type calcium channel generating a persistent inward current, PIC; Schwindt and Crill 1980, Hounsgaard and Kiehn 1985, 1989) is also responsible for the amplification of synaptic input in motoneurons. However, modeling studies utilizing only calcium-based PICs (Powers 1993, Booth et al. 1997, Elbasinouy et al. 2005) have been unable to reproduce the high degree of synaptic amplification observed in experimental preparations (Prather et al. 2001, Lee et al. 2003, Hultborn et al. 2003). The present work examines a theoretical amplification mechanism (electrotonic compression), based on a sodium PIC of dendritic origin, which acts to supplement the synaptic amplification due to the calcium PIC. The current goal is to test the "goodness-of-fit" of electrotonic compression with established mechanisms and behaviors. The findings of this modeling study support the concept of a dendritic sodium PIC which acts to reduce the attenuation of synaptic currents enroute to the motoneuron soma. Furthermore, it is suggested that the ratiometric expression of ion channels giving rise to this mechanism takes the form of a distribution "rule" applied ubiquitously across the dendritic tree, while the plateau-producing L-type calcium channels undergo a more discretized or regional distribution. This study demonstrates the power inherent to the controlled expansion of morphological complexity in an already complex model. While modeling studies are suitable testbeds for the evaluation of theoretical and/or experimentally intractable facets of physiology, great care and consideration should be given to the specification of models with high dimensionality. With the continual progression of our knowledge-base and computational capabilities, we can expect that more and more empirical observations will find their way into models of increasing complexity wherein the layers of embedded hypotheses are frequently implicit. It is therefore imperative that the neural modeling discipline adopt more rigorous methodologies to both accommodate and rein-in this growing complexity.

Le cerveau antérieur est l’aire cérébrale supportant les fonctions biologiques les plus complexes. Certaines altérations de son développement peuvent entraîner des maladies psychiatriques comme l’autisme ou encore la schizophrénie. Ainsi, les cellules du cerveau, appelées neurones, doivent être correctement positionnés au sein du cerveau et établir des connexions (appelées synapses) avec les autres neurones. Ce travail de thèse vise à mieux comprendre comment le positionnement des neurones et la formation des synapses sont régulés dans le cerveau antérieur. En premier lieu, nous avons étudié l’impact de l’activité neuronale sur le positionnement des différents types de neurones du bulbe olfactif. Dans un second temps, nous avons identifié le gène NeuroD2 comme régulateur majeur de la formation synaptique dans le cortex, l’absence de ce gène dans le cortex provoquant également l’altération du comportement social des souris. / The forebrain is the brain area that supports the most complex biological functions. Any alteration during its development can provoke psychiatric disorders such as autism or schizophrenia. The cells composing the brain, called neurons, must be adequately positioned and must establish functional connections (named synapses) with other neurons. This thesis work aims at understanding how neuronal positioning and synapse formation are controlled in the forebrain. In a first instance, we explored the impact of neuronal activity on the positioning of the different subtypes of olfactory bulb neurons. In a second instance, we identified the gene NeuroD2 as a major regulator of synapse formation in the cortex, the absence of this gene leading to social behavior deficits as well.

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