You’re Perfect, Now Change — Redefining the Role of Developmental Plasticity

The receptive field properties of neurons in the developing brain can in many cases be remarkably similar to those of adult neurons. This raises the question of why these same neurons need the capacity for such impressive developmental plasticity, most clearly demonstrated by the rewiring that occurs in response to sensory deprivation. The roles of developmental neuronal plasticity in the assimilation of neurons into a larger network, including temporal and cross-modal integration, are discussed

A Developmental Sensitive Period for Spike Timing-Dependent Plasticity in the Retinotectal Projection

The retinotectal projection in Xenopus laevis has been shown to exhibit correlation-based refinement of both anatomical and functional connectivity during development. Spike timing-dependent plasticity (STDP) is an appealing experimental model for correlation-based synaptic plasticity because, in contrast to plasticity induction paradigms using tetanic stimulation or sustained postsynaptic depolarization, its induction protocol more closely resembles natural physiological activity. In Xenopus tadpoles, where anatomical remodeling has been reported throughout much of the life of the animal, in vivo retinotectal STDP has only been examined under a limited set of experimental conditions. Using perforated-patch recordings of retina-evoked EPSCs in tectal neurons, we confirmed that repeatedly driving a retinotectal EPSP 5–10 ms prior to inducing an action potential in the postsynaptic cell, reliably produced timing-dependent long-term potentiation (t-LTP) of the retinotectal synapse in young wild type tadpoles (stages 41–44). At these stages, retinotectal timing-dependent long-term depression (t-LTD) also could be induced by evoking an EPSP to arrive 5–10 ms after an action potential in the tectal cell. However, retinotectal STDP using this standard protocol was limited to a developmental sensitive period, as we were unable to induce t-LTP or t-LTD after stage 44. Surprisingly, this STDP protocol also failed to induce reliable STDP in albino tadpoles at the early ages when it was effective in wild type pigmented animals. Nonetheless, low-frequency flashes to the eye produced a robust NMDA receptor-dependent retinotectal LTD in stage 47 albino tadpoles, demonstrating that the retinotectal synapse can nonetheless be modified in these animals using different plasticity paradigms

White Matter Plasticity Keeps the Brain in Tune: Axons Conduct While Glia Wrap.

Precise timing of neuronal inputs is crucial for brain circuit function and development, where it contributes critically to experience-dependent plasticity. Myelination therefore provides an important adaptation mechanism for vertebrate circuits. Despite its importance to circuit activity, the interplay between neuronal activity and myelination has yet to be fully elucidated. In recent years, significant attention has been devoted to uncovering and explaining the phenomenon of white matter (WM) plasticity. Here, we summarize some of the critical evidence for modulation of the WM by neuronal activity, ranging from human diffusion tensor imaging (DTI) studies to experiments in animal models. These experiments reveal activity-dependent changes in the differentiation and proliferation of the oligodendrocyte lineage, and in the critical properties of the myelin sheaths. We discuss the implications of such changes for synaptic function and plasticity, and present the underlying mechanisms of neuron-glia communication, with a focus on glutamatergic signaling and the axomyelinic synapse. Finally, we examine evidence that myelin plasticity may be subject to critical periods. Taken together, the present review aims to provide insights into myelination in the context of brain circuit formation and function, emphasizing the bidirectional interplay between neurons and myelinating glial cells to better inform future investigations of nervous system plasticity

White Matter Plasticity Keeps the Brain in Tune: Axons Conduct While Glia Wrap

Precise timing of neuronal inputs is crucial for brain circuit function and development, where it contributes critically to experience-dependent plasticity. Myelination therefore provides an important adaptation mechanism for vertebrate circuits. Despite its importance to circuit activity, the interplay between neuronal activity and myelination has yet to be fully elucidated. In recent years, significant attention has been devoted to uncovering and explaining the phenomenon of white matter (WM) plasticity. Here, we summarize some of the critical evidence for modulation of the WM by neuronal activity, ranging from human diffusion tensor imaging (DTI) studies to experiments in animal models. These experiments reveal activity-dependent changes in the differentiation and proliferation of the oligodendrocyte lineage, and in the critical properties of the myelin sheaths. We discuss the implications of such changes for synaptic function and plasticity, and present the underlying mechanisms of neuron–glia communication, with a focus on glutamatergic signaling and the axomyelinic synapse. Finally, we examine evidence that myelin plasticity may be subject to critical periods. Taken together, the present review aims to provide insights into myelination in the context of brain circuit formation and function, emphasizing the bidirectional interplay between neurons and myelinating glial cells to better inform future investigations of nervous system plasticity

Neurodevelopmental effects of chronic exposure to elevated levels of pro-inflammatory cytokines in a developing visual system

<p>Abstract</p> <p>Background</p> <p>Imbalances in the regulation of pro-inflammatory cytokines have been increasingly correlated with a number of severe and prevalent neurodevelopmental disorders, including autism spectrum disorder, schizophrenia and Down syndrome. Although several studies have shown that cytokines have potent effects on neural function, their role in neural development is still poorly understood. In this study, we investigated the link between abnormal cytokine levels and neural development using the <it>Xenopus laevis </it>tadpole visual system, a model frequently used to examine the anatomical and functional development of neural circuits.</p> <p>Results</p> <p>Using a test for a visually guided behavior that requires normal visual system development, we examined the long-term effects of prolonged developmental exposure to three pro-inflammatory cytokines with known neural functions: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α. We found that all cytokines affected the development of normal visually guided behavior. Neuroanatomical imaging of the visual projection showed that none of the cytokines caused any gross abnormalities in the anatomical organization of this projection, suggesting that they may be acting at the level of neuronal microcircuits. We further tested the effects of TNF-α on the electrophysiological properties of the retinotectal circuit and found that long-term developmental exposure to TNF-α resulted in enhanced spontaneous excitatory synaptic transmission in tectal neurons, increased AMPA/NMDA ratios of retinotectal synapses, and a decrease in the number of immature synapses containing only NMDA receptors, consistent with premature maturation and stabilization of these synapses. Local interconnectivity within the tectum also appeared to remain widespread, as shown by increased recurrent polysynaptic activity, and was similar to what is seen in more immature, less refined tectal circuits. TNF-α treatment also enhanced the overall growth of tectal cell dendrites. Finally, we found that TNF-α-reared tadpoles had increased susceptibility to pentylenetetrazol-induced seizures.</p> <p>Conclusions</p> <p>Taken together our data are consistent with a model in which TNF-α causes premature stabilization of developing synapses within the tectum, therefore preventing normal refinement and synapse elimination that occurs during development, leading to increased local connectivity and epilepsy. This experimental model also provides an integrative approach to understanding the effects of cytokines on the development of neural circuits and may provide novel insights into the etiology underlying some neurodevelopmental disorders.</p

Activity‐dependent alteration of early myelin ensheathment in a developing sensory circuit

Funder: Montreal Neurological Institute – University of Cambridge CollaborationFunder: Natural Sciences and Engineering Research Council of Canada; Id: http://dx.doi.org/10.13039/501100000038Abstract: Myelination allows for the regulation of conduction velocity, affecting the precise timing of neuronal inputs important for the development and function of brain circuits. In turn, myelination may be altered by changes in experience, neuronal activity, and vesicular release, but the links between sensory experience, corresponding neuronal activity, and resulting alterations in myelination require further investigation. We thus studied the development of myelination in the Xenopus laevis tadpole, a classic model for studies of visual system development and function because it is translucent and visually responsive throughout the formation of its retinotectal system. We begin with a systematic characterization of the timecourse of early myelin ensheathment in the Xenopus retinotectal system using immunohistochemistry of myelin basic protein (MBP) along with third harmonic generation (THG) microscopy, a label‐free structural imaging technique. Based on the mid‐larval developmental progression of MBP expression in Xenopus, we identified an appropriate developmental window in which to assess the effects of early temporally patterned visual experience on myelin ensheathment. We used calcium imaging of axon terminals in vivo to characterize the responses of retinal ganglion cells over a range of stroboscopic stimulation frequencies. Strobe frequencies that reliably elicited robust versus dampened calcium responses were then presented to animals for 7 d, and differences in the amount of early myelin ensheathment at the optic chiasm were subsequently quantified. This study provides evidence that it is not just the presence but also to the specific temporal properties of sensory stimuli that are important for myelin plasticity

A CANDLE for a deeper in-vivo insight

A new Collaborative Approach for eNhanced Denoising under Low-light Excitation (CANDLE) is introduced for the processing of 3D laser scanning multiphoton microscopy images. CANDLE is designed to be robust for low signal-to-noise ratio (SNR) conditions typically encountered when imaging deep in scattering biological specimens. Based on an optimized non-local means filter involving the comparison of filtered patches, CANDLE locally adapts the amount of smoothing in order to deal with the noise inhomogeneity inherent to laser scanning fluorescence microscopy images. An extensive validation on synthetic data, images acquired on microspheres and in vivo images is presented. These experiments show that the CANDLE filter obtained competitive results compared to a state-of-the-art method and a locally adaptive optimized non-local means filter, especially under low SNR conditions (PSNR < 8 dB). Finally, the deeper imaging capabilities enabled by the proposed filter are demonstrated on deep tissue in vivo images of neurons and fine axonal processes in the Xenopus tadpole brain.We want to thank Florian Luisier for providing free plugin of his PureDenoise filter. We also want to thank Markku Makitalo for providing the code of their OVST. This study was supported by the Canadian Institutes of Health Research (CIHR, MOP-84360 to DLC and MOP-77567 to ESR) and Cda (CECR)-Gevas-OE016. MM holds a fellowship from the Deutscher Akademischer Austasch Dienst (DAAD) and a McGill Principal's Award. ESR is a tier 2 Canada Research Chair. This work has been partially supported by the Spanish Health Institute Carlos III through the RETICS Combiomed, RD07/0067/2001. This work benefited from the use of ImageJ.Coupé, P.; Munz, M.; Manjón Herrera, JV.; Ruthazer, ES.; Collins, DL. (2012). A CANDLE for a deeper in-vivo insight. Medical Image Analysis. 16(4):849-864. https://doi.org/10.1016/j.media.2012.01.002S84986416