Plasticité du cortex visuel: «homéodynamie» des connexions neuronales et modèle d’effets d’antidépresseurs

Sensory informations are computed in the cortex by networks of co-activated neurons forming functional ensembles. Visual processing in the cortex underlies several aspects of neuronal characteristics such as anatomical, electrophysiological and molecular.  In the primary visual cortex,  neurons  display  selectivity  for  stimulus  features  such  as  orientation,  motion direction and spatial frequency. Each stimulus property elicits a maximal firing rate of specific neuronal populations.  Visual neurons display transient modifications of their response properties following prolonged exposure to an appropriate stimulus using visual learning or visual adaptation to a non-preferred stimulus.  The main objective of this thesis is to investigate the neuronal mechanisms underlying the visual processing during adaptation-induced plasticity in adult animals. These mechanisms are examined through different aspects: the neuronal connectivity, the neuronal selectivity, the electrical properties of neurons, and the effects of drugs (serotonin and fluoxetine). The tested model is the orientation columns of the primary visual cortex.  The present thesis is divided into four main chapters. The first chapter (A) focuses on the cortical reorganization following visual adaptation. The second chapter (B) examines the neuronal connectivity using pair-wise correlations and populational correlations of neuronal activities. The third chapter (C) further relate the previous aspects, i.e. the adaptation effects and the functional connectivity to the properties of neurons (two classes: regular-spiking and   fast-spiking neurons). Finally, the fourth chapter (D) investigates the coupling of visual adaptation with the local administration of drugs (serotonin and fluoxetine).      Methodology Using in vivo extracellular recordings of the neural activity in the primary visual cortex (V1) combined with intrinsic optical brain imaging, we record the spiking activity of neuronal populations and examine, from the multi-unit activity, the activity of individual neurons. The analysis of brain activity uses different algorithms: the electrophysiological distinctions between neurons are based on the trough-to-peak time of each spike (spike-width), the selectivity of neurons is based on the firing rate at different stimuli, and the functional connectivity uses a crosscorrelation computation. The usage of drugs is performed locally on the visual cortex (after craniotomy and removing of the dura). Results and conclusions In the first chapter, we demonstrate the ability of neurons to modify their selectivity to the presented stimuli following visual adaptation, exhibiting a well-organized reprogramming of the orientation columns; we attribute this result to a flexibility of functional units rather than rigid anatomical structures. Indeed, we observe an extensive restructuring of the complete orientation domain in order to refine the columnar organization where every stimulus is equally represented. This is further confirmed in the second chapter where in this case, the connectivity maps are investigated. In concordance with the previous results, the connectivity maps also exhibit restructuring but interestingly, neurons use a summative strategy to stabilize their total connectivity weights. These connectivity dynamics are examined in the third chapter in relation to electrophysiological properties of neurons. Indeed, two differently firing modes dissociate between two classes of neurons. Their distinct correlation dynamics point to the fact that they play different key roles in stimulus encoding within a neuronal population. Finally, in the last chapter, visual adaptation is coupled with the administration of serotonin and fluoxetine. Both drugs produce similar effects by facilitating the acquisition of the imposed stimulus. The non-preferred stimulus when adapted with the presence of the drug results in an increased firing rate of neurons at this particular stimulus. We present a neuronal model based on our findings to explain the fluctuations of firing with and without the drug.        This thesis provides new insights into how visual neurons adapt to change their selectivity in the interplay between their plastic ability and their homeostatic dynamic.

Keyphrases: Adaptation, Visual cortex, Plasticity, Neurons, Serotonin, Fluoxetine, Connectivity, Correlation