Neuroscience
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Sensory information in the brain is organized into spatial representations, including retinotopic, somatotopic, and tonotopic maps, as well as ocular dominance columns. The spatial representation of sensory inputs is thought to be a fundamental organizational principle that is important for information processing. Topographic maps are plastic throughout an animal's life, reflecting changes in development and aging of brain circuitry, changes in the periphery and sensory input, and changes in circuitry, for instance in response to experience and learning. Here, we review mechanisms underlying the role of activity in the development, stability and plasticity of topographic maps, focusing on recent work suggesting that the spatial information in the visual field, and the resulting spatiotemporal patterns of activity, provide instructive cues that organize visual projections.
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The main focus of research for which Friedrich Bonhoeffer's work is known in the Neuroscience community was pioneer experiments on how axonal projections could organize into "maps", what mechanisms are involved in axon guidance and involve gradients of guiding molecules, and isolation of the first such molecules, e.g. RAGS (ephrin A5) and RGM (repulsive guidance molecule). ⋯ In the mid-eighties, I made a 2-year stay in his lab and initiated a line of research on development of binocular connections in Mammals, particularly the guidance of retinal fibers to one or the other side of the brain. In this paper I recall these circumstances as they pertain to Neuroscience as it stood at the time, and explain as best as I can how his lab was a conducive setting for the discoveries made there and how Friedrich Bonhoeffer acted for me as a scientist and a tutor.
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Synapse formation between neurons is critical for proper circuit and brain function. Prior to activity-dependent refinement of connections between neurons, activity-independent cues regulate the contact and recognition of potential synaptic partners. Formation of a synapse results in molecular recognition events that initiate the process of synaptogenesis. ⋯ Of these families, the EphBs and ephrin-Bs are required during each phase of synaptic development from target selection, recruitment of synaptic proteins, and formation of spines to regulation of synaptic plasticity at glutamatergic spine synapses in the mature brain. These roles also place EphBs and ephrin-Bs as important regulators of human neurological diseases. This review will focus on the role of EphBs and ephrin-Bs at synapses.
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Investigating axonal behaviors while neurons are connecting with each other has been a challenge since the early studies on nervous system development. While molecule-driven axon pathfinding has been theorized by observing neurons at different developmental stages in vivo, direct observation and measurements of axon guidance behaviors required the invention of in vitro systems enabling to test the impact of molecules or cellular extracts on axons growing in vitro. With time, the development of novel in vivo approaches has confirmed the mechanisms highlighted in culture and has led in vitro systems to be adapted for cellular processes that are still inaccessible in intact organisms. We here review the evolution of these in vitro assays, which started with crucial contributions from the Bonhoeffer lab.
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Friedrich Bonhoeffer made seminal contributions to the study of axon guidance in the developing nervous system. His discoveries of key cellular and molecular mechanisms that dictate wiring specificity laid the foundation for countless investigators who have followed in his footsteps. Perhaps his most significant contribution was the cloning and characterization of members of the conserved ephrin family of repulsive axon guidance cues. ⋯ Specifically, we focus our discussion on the post-translational regulation of two major families of repulsive axon guidance factors: ephrin ligands and their Eph receptors, and slit ligands and their Roundabout (Robo) receptors. We will give special emphasis to the ways in which regulated endocytic trafficking events allow navigating axons to adjust their responses to repellant signals and how these trafficking events are intimately related to receptor signaling. By highlighting parallels and differences between the regulation of these two important repulsive axon guidance pathways, we hope to identify key outstanding questions for future investigation.