Papers by Bernard Poulain
HAL (Le Centre pour la Communication Scientifique Directe), 2015
Philosophical Transactions of the Royal Society B, Jan 5, 2014
Cite this article: Khelfaoui M et al. 2014 Lack of the presynaptic RhoGAP protein oligophrenin1 l... more Cite this article: Khelfaoui M et al. 2014 Lack of the presynaptic RhoGAP protein oligophrenin1 leads to cognitive disabilities through dysregulation of the cAMP/PKA signalling pathway.
Pathologie Biologie
ABSTRACT
Toxins, 2020
Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurologic... more Epsilon toxin (ETX), produced by Clostridium perfringens types B and D, causes serious neurological disorders in animals. ETX can bind to the white matter of the brain and the oligodendrocytes, which are the cells forming the myelin sheath around neuron axons in the white matter of the central nervous system. After binding to oligodendrocytes, ETX causes demyelination in rat cerebellar slices. We further investigated the effects of ETX on cerebellar oligodendrocytes and found that ETX induced small transmembrane depolarization (by ~ +6.4 mV) in rat oligodendrocytes primary cultures. This was due to partial inhibition of the transmembrane inward rectifier potassium current (Kir). Of the two distinct types of Kir channel conductances (~25 pS and ~8.5 pS) recorded in rat oligodendrocytes, we found that ETX inhibited the large-conductance one. This inhibition did not require direct binding of ETX to a Kir channel. Most likely, the binding of ETX to its membrane receptor activates intrac...
Neurosecretion: Secretory Mechanisms, 2020
The mechanism by which bacterial toxins alter or interfere with secretion mechanisms are addresse... more The mechanism by which bacterial toxins alter or interfere with secretion mechanisms are addressed in this chapter. After a brief description of the general mechanism of bacterial exotoxins, examples of key toxins affecting neurosecretion are commented upon. These comprise the botulinum and tetanus neurotoxins (BoNT and TeNT), which are toxins that divert synaptic vesicle (SV) recycling to enter nerve endings, and impair exocytosis by cleaving the soluble N-ethyl-maleimide-sensitive-factor attachment receptors (SNAREs). Given the important role of Rho, Rac, CDC42 GTPase, and F-actin in the vesicle/granule intracellular traffic and secretion processes, we address several examples of key bacterial cytotoxins affecting their cellular functions. We also briefly comment on the action of a few bacterial toxins that potentiate release of neurotransmitters.
From planification to execution, cerebellar microcircuits encode different features of skilled mo... more From planification to execution, cerebellar microcircuits encode different features of skilled movements. However, it is unknown whether cerebellar synaptic connectivity maps encode movement features in a motor context specific manner. Here we investigated the spatial organization of excitatory synaptic connectivity in mice cerebellar cortex in different locomotor contexts: during development and in normal, trained or altered locomotor conditions. We combined optical, electrophysiological and graph modelling approaches to describe synaptic connectivity between granule cells (GCs) and Purkinje cells (PCs). Synaptic map maturation during development revealed a critical period in juvenile animals before the establishment of a stereotyped functional organization in adults. However, different locomotor conditions lead to specific GC-PC connectivity maps in PCs. Ultimately, we demonstrated that the variability in connectivity maps directly accounts for individual specific behavioral featu...
In the cerebellum, molecular layer interneurons (MLIs) play an essential role in motor behavior b... more In the cerebellum, molecular layer interneurons (MLIs) play an essential role in motor behavior by exerting precise temporal control of Purkinje cells, the sole output of the cerebellar cortex. The recruitment of MLIs is tightly controlled by the release of glutamate from granule cells (GCs) during high-frequency activities. Here we study how single MLIs are recruited by their distinct unitary GC inputs during burst of GC stimulations. Stimulation of individual GC-MLI synapses revealed four classes of connections segregated by their profile of short-term plasticity. Each class of connection differentially drives MLI recruitment. Molecular and ultrastructural analyses revealed that GC-MLI synaptic diversity is underlain by heterogeneous expression of synapsin II at individual GC terminals. In synapsin II knock-out mice, the number of classes is reduced to profiles associated with slow MLI recruitment. Our study reveals that molecular diversity across GC terminals enables diversity in...
Toxins, 2019
Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and c... more Botulinum neurotoxins (BoNTs) are the most lethal toxins among all bacterial, animal, plant and chemical poisonous compounds. Although a great effort has been made to understand their mode of action, some questions are still open. Why, and for what benefit, have environmental bacteria that accidentally interact with their host engineered so diverse and so specific toxins targeting one of the most specialized physiological processes, the neuroexocytosis of higher organisms? The extreme potency of BoNT does not result from only one hyperactive step, but in contrast to other potent lethal toxins, from multi-step activity. The cumulative effects of the different steps, each having a limited effect, make BoNTs the most potent lethal toxins. This is a unique mode of evolution of a toxic compound, the high potency of which results from multiple steps driven by unknown selection pressure, targeting one of the most critical physiological process of higher organisms.
The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are d... more The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are differentially poised for exocytosis shapes short-term plasticity at depressing synapses. Here, we used in vitro recording and modeling of synaptic activity at the facilitating mice cerebellar granule cell to Purkinje cell synapse to demonstrate the existence of two sub-pools of vesicles in the RRP that can be differentially recruited upon fast changes in the stimulation frequency. We show that upon low-frequency stimulation, a population of fully-releasable vesicles is silenced, leading to full blockage of synaptic transmission. A second population of vesicles, reluctant to release by simple stimuli, is recruited in a millisecond time scale by high-frequency stimulation to support an ultrafast recovery of neurotransmitter release after low-frequency depression. The frequency-dependent mobilization or silencing of sub-pools of vesicles in granule cell terminals should play a major role in...
Expert Opinion on Drug Discovery, 2017
Bossu (2017): Organotypic cultures of cerebellar slices as a model to investigate demyelinating d... more Bossu (2017): Organotypic cultures of cerebellar slices as a model to investigate demyelinating disorders, Expert Opinion on Drug Discovery,
European Journal of Neuroscience, 2009
Bacterial Toxins, 2000
ABSTRACT
Current Topics in Microbiology and Immunology, 1995
Methods in Neurosciences, 1992
Publisher Summary This chapter discusses the mode of action on neurotransmitter release by botuli... more Publisher Summary This chapter discusses the mode of action on neurotransmitter release by botulinal neurotoxins. Botulinal neurotoxins (BoNTs) are among the most potent biological agents known so far. Seven immunologically distinguishable forms of these neuroparalytic proteins, designated as types A, B, C 1 , D, E, F, and G, are produced by different strains of the anaerobic, spore-forming bacterium, Clostridium botulinum. These neurotoxins are synthesized as single-chain proteins. Depending on the physiology of the bacterium and the conditions of the bacterial culture, they may be cleaved into a di-chain protein. The possibility that BoNTs can affect presynaptic Ca 2+ entry and/or intraterminal Ca 2+ levels has been tested. The chapter describes a method in which microelectrodes is inserted in the perineurium of small preterminal nerve bundles to record electric signals related to membrane currents. It is found that BoNT type A or D poisoned endings display normal Ca 2+ currents.
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Papers by Bernard Poulain