Bases neurales de la représentation de soi chez le primate non-humain grâce à l'imagerie par résonance magnétique fonctionnelle (IRMf)

The aim of this thesis is to investigate the neural basis of self-representation in the non human primate. We studied the multimodal convergence both 1) at the area level precisely mapping auditory, tactile and visual convergence in the intraparietal sulcus and 2) at the whole brain level capturing the spatial pattern of visuo-tactile cortical convergence. We also investigated the neural network subserving multisensory integration in a dynamical visuo tactile context, showing that the strongest behavioral and cortical are obtained when the visual stimuli is predictive of the tactile stimulus rather than during simultaneous presentations. Finally, we studied the representation of space by characterizing the neural bases of near space and far space in a real naturalistic environment, thus providing the neural grounds for the observed behavioral and neuropsychological dissociation between near and far space processingL'objectif de cette thèse est d'identifier les bases neurales de la représentation de soi chez le primate non-humain, par une approche d'imagerie par résonnance magnétique fonctionnelle. Nous avons pour cela étudié la convergence multimodale 1) à l'échelle de l'aire par la description de la cartographie du sillon intraparietal dans un contexte de stimulations auditives, tactiles et visuelles et 2) à l'échelle du cerveau entier où nous décrivons précisément les sites de convergence visuo-tactile au niveau cortical. Nous avons également étudié le phénomène d'intégration multisensorielle dans un contexte visuo-tactile dynamique, pour lequel nous montrons que les effets comportementaux (étude psychophysique menée chez l'homme) et le réseau d'activations cortical sont maximisés quand le stimulus visuel prédit le stimulus tactile plutôt que lors de leur présentation simultanée. Enfin, nous avons étudié la représentation de l'espace en caractérisant les bases neurales de l'espace proche et de l'espace lointain à partir d'un dispositif expérimental naturaliste et nous montrons l'existence de deux réseaux corticaux qui traitent séparément les informations appartenant à l'espace proche et à l'espace lointai

The murine orthologue of the Golgi-localized TPTE protein provides clues to the evolutionary history of the human TPTE gene family

Abstract.: The human TPTE gene encodes a testis-specific protein that contains four potential transmembrane domains and a protein tyrosine phosphatase motif, and shows homology to the tumor suppressor PTEN/MMAC1. Chromosomal mapping revealed multiple copies of the TPTE gene present on the acrocentric chromosomes 13, 15, 21 and 22, and the Y chromosome. Zooblot analysis suggests that mice may possess only one copy of TPTE. In the present study, we report the isolation and initial characterization of the full-length cDNA of the mouse homologue Tpte. At least three different mRNA transcripts (Tpte.a, b, c) are produced via alternative splicing, encoding predicted proteins that would contain four potential transmembrane domains and a protein tyrosine phosphatase motif. Transfection of a 5′EGFP-TPTE fusion protein in Hela cells revealed an intracellular localization within the Golgi apparatus. Tpte was mapped by radiation hybrid to a region of mouse chromosome 8 that shows conserved synteny with human 13q14.2-q21 between NEK3 and SGT1. This region of the human genome was found to contain a partial, highly diverged copy of TPTE that is likely to represent the ancestral copy from which the other copies of TPTE arose through duplication events. The Y chromosome copy of TPTE is a pseudogene and is not therefore involved in the testis expression of this gene famil

Neural basis of self-representation in the non-human primate thanks to functional magnetic resonance imaging (fMRT)

L'objectif de cette thèse est d'identifier les bases neurales de la représentation de soi chez le primate non-humain, par une approche d'imagerie par résonnance magnétique fonctionnelle. Nous avons pour cela étudié la convergence multimodale 1) à l'échelle de l'aire par la description de la cartographie du sillon intraparietal dans un contexte de stimulations auditives, tactiles et visuelles et 2) à l'échelle du cerveau entier où nous décrivons précisément les sites de convergence visuo-tactile au niveau cortical. Nous avons également étudié le phénomène d'intégration multisensorielle dans un contexte visuo-tactile dynamique, pour lequel nous montrons que les effets comportementaux (étude psychophysique menée chez l'homme) et le réseau d'activations cortical sont maximisés quand le stimulus visuel prédit le stimulus tactile plutôt que lors de leur présentation simultanée. Enfin, nous avons étudié la représentation de l'espace en caractérisant les bases neurales de l'espace proche et de l'espace lointain à partir d'un dispositif expérimental naturaliste et nous montrons l'existence de deux réseaux corticaux qui traitent séparément les informations appartenant à l'espace proche et à l'espace lointainThe aim of this thesis is to investigate the neural basis of self-representation in the non human primate. We studied the multimodal convergence both 1) at the area level precisely mapping auditory, tactile and visual convergence in the intraparietal sulcus and 2) at the whole brain level capturing the spatial pattern of visuo-tactile cortical convergence. We also investigated the neural network subserving multisensory integration in a dynamical visuo tactile context, showing that the strongest behavioral and cortical are obtained when the visual stimuli is predictive of the tactile stimulus rather than during simultaneous presentations. Finally, we studied the representation of space by characterizing the neural bases of near space and far space in a real naturalistic environment, thus providing the neural grounds for the observed behavioral and neuropsychological dissociation between near and far space processin

The Caenorhabditis elegans ortholog of C21orf80, a potential new protein O-fucosyltransferase, is required for normal development

Down syndrome (DS), as a phenotypic result of trisomy 21, is the most frequent aneuploidy at birth and the most common known genetic cause of mental retardation. DS is also characterized by other phenotypes affecting many organs, including brain, muscle, heart, limbs, gastrointestinal tract, skeleton, and blood. Any of the human chromosome 21 (Hsa21) genes may contribute to some of the DS phenotypes. To determine which of the Hsa21 genes are involved in DS, the effects of disrupting and overexpressing individual human gene orthologs in model organisms, such as the nematode Caenorhabditis elegans, can be analyzed. Here, we isolated and characterized C21orf80 (human chromosome 21 open reading frame 80), a potential novel protein O-fucosyltransferase gene that encodes three alternatively spliced transcripts. Transient expression of tagged C21orf80 proteins suggests a primary intracellular localization in the Golgi apparatus. To gain insight into the biological role of C21orf80 and its potential role in DS, we isolated its C. elegans ortholog, pad-2, and performed RNA interference (RNAi) and overexpression experiments. pad-2(RNAi) embryos showed failure to undergo normal morphogenesis. Transgenic worms with elevated dosage of pad-2 displayed severe body malformations and abnormal neuronal development. These results show that pad-2 is required for normal development and suggest potential roles for C21orf80 in the pathogenesis of DS

Cortical networks for encoding near and far space in the non-human primate

International audienc

Reward activations and face fields in monkey cingulate motor areas

International audienc

Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time

Transcranial magnetic stimulation (TMS) is increasingly used to perturb targeted human brain sites non-invasively, to test for causal effects on performance of cognitive tasks. TMS might also be used in non-human primates to complement invasive work and compare with human studies. Here, we targeted the frontal eye fields (FEF) in two macaques with a continuous theta-burst (cTBS) protocol, testing the impact on visually guided saccades. After unilateral cTBS over the FEF in either hemisphere, a small (mean 7 ms) but highly consistent decrease in saccadic reaction times (RTs) was observed. Lower latencies arose for saccades both contra- and ipsilateral to the stimulated FEF after cTBS. These results provide the first demonstration that TMS can be used to affect saccadic behavior in non-human primates. The unexpectedly bilateral impact on RTs may reflect an impact on 'fixation' neurons in the FEF and/or transcallosal modulation of both FEFs induced by unilateral cTBS. In either case, this study demonstrates a clear behavioral effect induced by TMS in awake behaving monkeys performing a cognitive task. This opens new opportunities for investigating the causal roles of targeted brain areas in behavior, for measuring physiological consequences of TMS in the primate brain, and ultimately for human-monkey comparisons.status: publishe

Transcranial magnetic stimulation of macaque frontal eye fields decreases saccadic reaction time

Transcranial magnetic stimulation (TMS) is increasingly used to perturb targeted human brain sites non-invasively, to test for causal effects on performance of cognitive tasks. TMS might also be used in non-human primates to complement invasive work and compare with human studies. Here, we targeted the frontal eye fields (FEF) in two macaques with a continuous theta-burst (cTBS) protocol, testing the impact on visually guided saccades. After unilateral cTBS over the FEF in either hemisphere, a small (mean 7 ms) but highly consistent decrease in saccadic reaction times (RTs) was observed. Lower latencies arose for saccades both contra- and ipsilateral to the stimulated FEF after cTBS. These results provide the first demonstration that TMS can be used to affect saccadic behavior in non-human primates. The unexpectedly bilateral impact on RTs may reflect an impact on 'fixation' neurons in the FEF and/or transcallosal modulation of both FEFs induced by unilateral cTBS. In either case, this study demonstrates a clear behavioral effect induced by TMS in awake behaving monkeys performing a cognitive task. This opens new opportunities for investigating the causal roles of targeted brain areas in behavior, for measuring physiological consequences of TMS in the primate brain, and ultimately for human-monkey comparisons