Bone marrow transplantation chemotherapy disrupts regenerative brain cell populations

International audienc

Youth Comes But Once in a Lifetime for Adult-Born Neurons

Series: Seminal Neuroscience Papers 1978–2017International audienceUsing new methods to functionally dissect circuits, two papers from 2015 found enhanced synaptic properties of the inputs and outputs of hippocampal adult-born neurons specifically during a critical period of their development. These studies provided a circuit-level view of unique roles for new neurons and how they cope with the ever-changing environment

Adult neurogenesis beyond the niche: its potential for driving brain plasticity

Adult neurogenesis emerges as a tremendous form of plasticity with the continuous addition and loss of neurons in the adult brain. It is unclear how preexisting adult circuits generated during development are capable of modifying existing connections to accommodate the thousands of new synapses formed and exchanged each day. Here we first make parallels with sensory deprivation studies and its ability to induce preexisting non-neurogenic adult circuits to undergo massive reorganization. We then review recent studies that show high structural and synaptic plasticity in circuits directly connected to adult-born neurons. Finally, we propose future directions in the field to decipher how host circuits can accommodate new neuron integration and to determine the impact of adult neurogenesis on global brain plasticity.Fil: Sailor, Kurt A.. Centre National de la Recherche Scientifique; Francia. Instituto Pasteur; FranciaFil: Schinder, Alejandro Fabián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Lledo, Pierre-Marie. Centre National de la Recherche Scientifique; Francia. Instituto Pasteur; Franci

XTRPC1-dependent chemotropic guidance of neuronal growth cones

Calcium arising through release from intracellular stores and from influx across the plasma membrane is essential for signalling by specific guidance cues and by factors that inhibit axon regeneration. The mediators of calcium influx in these cases are largely unknown. Transient receptor potential channels (TRPCs) belong to a superfamily of Ca2+-permeable, receptor-operated channels that have important roles in sensing and responding to changes in the local environment. Here we report that XTRPC1, a Xenopus homolog of mammalian TRPC1, is required for proper growth cone turning responses of Xenopus spinal neurons to microscopic gradients of netrin-1, brain-derived neurotrophic factor and myelin-associated glycoprotein, but not to semaphorin 3A. Furthermore, XTRPC1 is required for midline guidance of axons of commissural interneurons in the developing Xenopus spinal cord. Thus, members of the TRPC family may serve as a key mediator for the Ca2+ influx that regulates axon guidance during development and inhibits axon regeneration in adulthood

Persistent Structural Plasticity Optimizes Sensory Information Processing in the Olfactory Bulb

International audienceIn the mammalian brain, the anatomical structure of neural circuits changes little during adulthood. As a result, adult learning and memory are thought to result from specific changes in synaptic strength. A possible exception is the olfactory bulb (OB), where activity guides interneuron turnover throughout adulthood. These adult-born granule cell (GC) interneurons form new GABAergic synapses that have little synaptic strength plasticity. In the face of persistent neuronal and synaptic turnover, how does the OB balance flexibility, as is required for adapting to changing sensory environments, with perceptual stability? Here we show that high dendritic spine turnover is a universal feature of GCs, regardless of their developmental origin and age. We find matching dynamics among postsynaptic sites on the principal neurons receiving the new synaptic inputs. We further demonstrate in silico that this coordinated structural plasticity is consistent with stable, yet flexible, decorrelated sensory representations. Together, our study reveals that persistent, coordinated synaptic structural plasticity between interneurons and principal neurons is a major mode of functional plasticity in the OB

Hematopoietic stem cell transplantation chemotherapy causes microglia senescence and peripheral macrophage engraftment in the brain

International audienceHematopoietic stem cell transplantation (HSCT) is a therapy used for multiple malignant and nonmalignant diseases, with chemotherapy used for pretransplantation myeloablation. The post-HSCT brain contains peripheral engrafted parenchymal macrophages, despite their absence in the normal brain, with the engraftment mechanism still undefined. Here we show that HSCT chemotherapy broadly disrupts mouse brain regenerative populations, including a permanent loss of adult neurogenesis. Microglial density was halved, causing microglial process expansion, coinciding with indicators of broad senescence. Although microglia expressed cell proliferation markers, they underwent cell cycle arrest in S phase with a majority expressing the senescence and antiapoptotic marker p21. In vivo single-cell tracking of microglia after recovery from chemical depletion showed loss of their regenerative capacity, subsequently replaced with donor macrophages. We propose that HSCT chemotherapy causes microglial senescence with a gradual decrease to a critical microglial density, providing a permissive niche for peripheral macrophage engraftment of the brain

New Approach to Accelerated Image Annotation by Leveraging Virtual Reality and Cloud Computing

International audienceThree-dimensional imaging is at the core of medical imaging and is becoming a standard in biological research. As a result, there is an increasing need to visualize, analyze and interact with data in a natural three-dimensional context. By combining stereoscopy and motion tracking, commercial virtual reality (VR) headsets provide a solution to this critical visualization challenge by allowing users to view volumetric image stacks in a highly intuitive fashion. While optimizing the visualization and interaction process in VR remains an active topic, one of the most pressing issue is how to utilize VR for annotation and analysis of data. Annotating data is often a required step for training machine learning algorithms. For example, enhancing the ability to annotate complex three-dimensional data in biological research as newly acquired data may come in limited quantities. Similarly, medical data annotation is often time-consuming and requires expert knowledge to identify structures of interest correctly. Moreover, simultaneous data analysis and visualization in VR is computationally demanding. Here, we introduce a new procedure to visualize, interact, annotate and analyze data by combining VR with cloud computing. VR is leveraged to provide natural interactions with volumetric representations of experimental imaging data. In parallel, cloud computing performs costly computations to accelerate the data annotation with minimal input required from the user. We demonstrate multiple proof-of-concept applications of our approach on volumetric fluorescent microscopy images of mouse neurons and tumor or organ annotations in medical images

The neuropeptide VIP potentiates intestinal innate type 2 and type 3 immunity in response to feeding

International audienceThe nervous system and the immune system both rely on an extensive set of modalities to perceive and act on perturbations in the internal and external environments. During feeding, the intestine is exposed to nutrients that may contain noxious substances and pathogens. Here we show that Vasoactive Intestinal Peptide (VIP), produced by the nervous system in response to feeding, potentiates the production of effector cytokines by intestinal type 2 and type 3 innate lymphoid cells (ILC2s and ILC3s). Exposure to VIP alone leads to modest activation of ILCs, but strongly potentiates ILCs to concomitant or subsequent activation by the inducer cytokines IL-33 or IL-23, via mobilization of cAMP and energy by glycolysis. Consequently, VIP increases resistance to intestinal infection by the helminth Trichuris muris and the enterobacteria Citrobacter rodentium. These findings uncover a functional neuro-immune crosstalk unfolding during feeding that increases the reactivity of innate immunity necessary to face potential threats associated with food intak