Environmental events simultaneously transduced by more than one sensory modality underlie multisensory processing in the CNS. While most studies of multisensory processing examine functional effects, none have evaluated the influence of local or columnar circuitry. The goal of the present study is to examine of local features of the ferret lateral rostral suprasylvian sulcus (LRSS), a multisensory cortex. Immunostaining revealed the cytoarchitectonic features of the LRSS: thick supragranular layers, a narrow layer IV, and moderately stained but differentiated infragranular layers. Golgi-Cox techniques were used with light microscopy and digital reconstruction to document neuronal morphology. Among the 90 reconstructed neurons, 4 distinct forms or pyramidal and 2 types of non-pyramidal neurons were found. Measurement of maximal dendritic spread indicates that a cortical column in the LRSS was 250.9 um in diameter. These results describe local features of the LRSS upon which future experiments of intrinsic circuitry will be based.

La formation de la mémoire spatiale est un mécanisme complexe qui transforme les informations récemment acquises en traces mnésique robustes à long terme. D’un point de vue moléculaire, ces phénomènes sont dépendants de l’expression de deux formes opposées de plasticité synaptique ; la potentialisation à long terme (LTP) et la dépression à long terme (LTD). L’induction de la LTP/LTD dépend de la fine régulation entre des kinases et des phosphatases sensibles au Ca2+ qui vont activer respectivement la LTP et la LTD dans la densité postsynaptique (PSD). Cette régulation met également en jeu des interactions en avale entre les récepteurs et des protéines d’échafaudages spécialisées au sein de la PSD. Scribble1 (Scrib1) est une de ces protéines d’échafaudage appartenant à la famille des LAP (leucine-rich repeats & PDZ domains) avec 16 répétitions riches en leucine et 4 domaines PDZ (PSD-95/Dlg/ZO-1). Lors de cette étude, nous avons développé de souris « knock-out » conditionnelles avec une délétion complète de la Scrib1 dans les principaux neurones de l’encéphale antérieur, dont les neurones excitateurs de l’hippocampe, grâce au système Cre-lox (Scrib1f/f,CaMKII-cre). Les souris Scrib1f/f,CaMKII-cre présentent une altération de la morphologie des dendrites apicales sans modification de la morphologie ni de la densité des épines dans la région CA1 de l’hippocampe. Sur le plan fonctionnel, les neurones du CA1 des souris Scrib1f/f,CaMKII-cre présentent une augmentation du nombre de synapses silencieuses (non-fonctionnelles). Ceci réduit le nombre de synapses actives et entraine une diminution globale de la transmission basale des synapses CA3-CA1 comparée aux synapses Scrib1f/f. Les souris Scrib1f/f,CaMKII-cre montrent une augmentation de la LTP mais sont incapables d’exprimer une LTD ni la depotentiation à long terme. De plus, des protocoles de LTD induisent une LTP chez ces souris. Au niveau moléculaire, nous avons mis en évidence une interaction directe au sein des synapses entre Scrib1 et la phosphatase PP2A impliquée dans la LTD. De plus, l’absence de Scrib1 entraine une réduction des niveaux de PP2A dans la PSD chez les souris Scrib1f/f,CaMKII-cre. Ceci implique une diminution de l’activation de la voie de signalisation de la LTD via PP2A au profit de celle de la CAMKII et la LTP, ce qui pourrait expliquer l’induction d’une LTP à la place d’une LTD chez les souris Scrib1f/f,CaMKII-cre. Sur le plan cognitif, les souris Scrib1f/f,CaMKII-cre présentent des déficits dans la flexibilité de l’apprentissage spatial comparées aux souris Scrib1f/f. Chez les souris Scrib1f/f,CaMKII-cre, la la mémoire spatiale à court terme n’était pas altérée tandis que la mémoire à long terme était déficiente. Ainsi, ces données révèlent un rôle majeur de Srib1 dans consolidation de la mémoire spatiale. Lors de cette étude, nous avons montré un rôle pour Scrib1 dans les connections et la morphologie des neurones CA1, ainsi que la conversion fonctionnelle des synapses silencieuses en synapses actives. D’une manière importante, Scrib1 permet l’expression de la plasticité synaptique bidirectionnelle à travers une interaction avec PP2A et module la formation de la mémoire spatiale à long terme. / Spatial memory formation is a complex process that transforms newly-acquired information into long-lasting and solid memories. Molecularly, these phenomena rely on the expression of two opposite forms of synaptic plasticity; long-term potentiation (LTP) and long-term depression (LTD). LTP/LTD induction relies on a fine balance between Ca2+-sensitive kinases and phosphatases that activate specific pathways of either LTP or LTD, respectively. This regulation also involves downstream interactions between receptors and highly specialized scaffold proteins, at the PSD. Scribble1 (Scrib1) is a scaffold protein that belongs to the LAP (leucine-rich repeats and PDZ domains) protein family, with 16 leucine rich repeats and 4 PDZ (PSD-95/Dlg/ZO-1) domains. Here, we developed conditional knock-out mice with a complete loss of Scrib1 expression in the major neurons of the postnatal forebrain, including hippocampal excitatory neurons, using the Cre-Lox system (Scrib1f/f,CaMKII-cre). Scrib1f/f,CaMKII-cre presented altered morphology of apical dendrites but intact spine density and spine morphology in the CA1 region. Functionally, we found increased number of silent (non-functional) synapses that decreases the number of active synapses in Scrib1f/f,CaMKII-cre CA1 neurons leading to a global decrease in basal glutamatergic synaptic transmission at CA3-CA1 synapses compared to Scrib1f/f synapses. Scrib1f/f,CaMKII-cre synapses displayed enhanced LTP but were unable to express LTD or long-term depotentiation. More strikingly, LTD-inducing protocols generated LTP in Scrib1f/f,CaMKII-cre synapses. Molecularly, we revealed a direct interaction between Scrib1 and the phosphatase PP2A that signals LTD at the synapse. Moreover, we found that the absence of Scrib1 results in a reduction of synaptic PP2A levels in Scrib1f/f,CaMKII-cre mice. This probably leads to a decrease in PP2A signaling pathway activation which favors the competing pathway downstream CaMKII resulting in LTP induction instead of LTD in Scrib1f/f,CaMKII-cre mice. On the cognitive level, we found that spatial learning was slower and inflexible in Scrib1f/f,CaMKII-cre compared to Scrib1f/f mice. Short-term spatial memory was intact while long-term memory was impaired. These results argue for an important role of Scrib1 in spatial memory consolidation. We here report that Scrib1 is important for appropriate neuronal shaping and wiring of CA1 neurons as well as functional conversion of silent synapses into active ones. Importantly, it allows bidirectional synaptic plasticity through interaction with PP2A and modulates long-term spatial memory formation

There have been a number of computational modelling studies that aim to replicate the cerebellar Purkinje cell, though these typically use the morphology of rodent cells. While many species, including rodents, display intricate dendritic branching, it is not a universal feature among Purkinje cells. This study uses morphological reconstructions of 24 Purkinje cells from seven species to explore the changes that occur to the cell through evolution and examine whether this has an effect on the processing capacity of the cell. This is achieved by combining several modes of study in order to gain a comprehensive overview of the variations between the cells in both morphology and behaviour. Passive and active computational models of the cells were created, using the same electrophysiological parameters and ion channels for all models, to characterise the voltage attenuation and electrophysiological behaviour of the cells. These results and several measures of branching and size were then used to look for clusters in the data set using machine learning techniques. They were also used to visualise the differences within each species group. Information theory methods were also employed to compare the estimated information transfer from input to output across each cell. Along with a literature review into what is known about Purkinje cells and the cerebellum across the phylogenetic tree, these results show that while there are some obvious differences in morphology, the variation within species groups in electrophysiological behaviour is often as high as between them. This suggests that morphological changes may occur in order to conserve behaviour in the face of other changes to the cerebellum.