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TiNS Special Issue: Circuit Development and Remodeling
Editorial
TiNS Special Issue: Circuit Development and Remodeling Andrew M. Clark Trends in Neurosciences, Cell Press, 600 Technology Square 5th Floor, Cambridge, MA 02139, USA
This month’s issue of Trends in Neurosciences focuses on the mechanisms underlying the construction and refinement of neural circuits, highlighting the important role that learning and injury, in addition to normal developmental processes, play in shaping both form and function in the juvenile and mature brain. Understanding circuit development and remodeling is important for formulating a more complete picture of both normal and pathological brain function, as circuits are considered to be a fundamental computational unit within the nervous system and circuit dysfunction is increasingly seen as central to many neurological and psychiatric diseases. During development, neural progenitor cells (NPCs) give rise to a myriad array of excitatory and inhibitory neurons and glia. Self-renewal, multipotency, and fate determination in NPCs is subject to a host of factors, including the action of the basic helix–loop–helix (bHLH) family of transcription factors. In this issue, Imayoshi and Kageyama review recent research into the effects of differential temporal expression of particular bHLH factors on fate determination, the versatile actions of particular bHLH factors on NPC function, and the structure of the bHLH signaling pathway. Excitatory–inhibitory (E–I) balance, the ratio of excitatory to inhibitory synaptic inputs to a given cell, is increasingly appreciated as a key determinant of network function, strongly affecting gain control at both the cellular and network level. Accumulating evidence suggests imbalances in E–I ratio exist in epilepsy and some forms of autism. In this issue, de Wit and Ghosh review work on the molecular organization of excitatory and inhibitory synapses, focusing on the role of leucine-rich repeat (LRR) proteins in coordinating synapse formation, differentiation, and plasticity. Proper routing of axons to their targets is essential for neural circuits to be wired correctly during development. This process is dependent upon a host of attractive and repulsive signals, and is central to appropriate function of local- and long-range circuits. In a Feature Review in this issue, Chedotal details the genetic and molecular mechanisms governing axon guidance in subsets of commissural neurons, cells whose axons cross the midline, in the brain and spinal cord that control and coordinate locomotion. For many years, conventional wisdom held that there are no new-born neurons in the juvenile and adult brain. Corresponding author: Clark, A.M. ([email protected]). 0166-2236/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tins.2014.09.004
Now, it is widely acknowledged that neurogenesis does continue past development within several specialized zones in the mature brain. In these pages, Lim and Buylla discuss recent work examining the organization of neural stem cells (NSCs) in one of these niches, the so-called ventricular–subventricular zone (V–SVZ), which gives rise to various types of neurons that are eventually integrated into olfactory bulb circuits. Recent findings regarding neuronal production and the epigenetic mechanisms that maintain adult neurogenesis in the V–SVZ have the capacity to impact our understanding of neural development more broadly. Axonal degeneration occurs normally in development as initially broad and non-selective connectivity is shaped by experience. Axon loss is also a feature of injury and several diseases of the nervous system; thus, identifying mechanisms of axonal preservation and survival are important both for understanding neural development and developing methods for treating and preventing neurodegenerative disease. In this issue, Pease and Segal review recent research into the mechanisms underlying axonal survival in normal development and following insult or disease. Following insult, severed axons in the adult CNS have little capacity for regeneration, a fact that limits functional recovery following severe injury. In recent years, the mechanisms underlying this inhibition of axonal re-growth, as well as the mechanisms underlying post-injury sprouting and reorganization, have begun to yield to empirical investigation. In the pages of this issue, Chen and Zheng detail recent progress in this area, arguing that the days of therapeutic stimulation of directed circuit re-wiring are within reach. Not all new synaptic connections formed following injury are beneficial, as seen from work examining synaptic reorganization following retinal degeneration. Synaptic remodeling during development, or following injury or disease can be readily studied in the retina, due to its exquisite and well-understood organization and connectivity. Here, D’Orazi, Suzuki, and Wong review recent discoveries concerning the mechanisms which govern retinal circuit remodeling during development, and discuss how establishment of aberrant patterns of connectivity following damage or disease might limit retinal function. Finally, it is now well-appreciated that everyday experience is constantly sculpting and shaping neural circuits. Accumulating evidence suggests that connectivity In this issue, Caroni et al. outline recent work examining this process of dynamic circuit re-organization, via selective addition, validation and elimination of synapses, across molecular, cellular, and systems levels. Trends in Neurosciences, October 2014, Vol. 37, No. 10
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Editorial Obviously, there is too much exciting work being done on the development and remodeling of neural circuits to cover the subject exhaustively in the pages of a single issue. Although the articles included here thus only represent a sampling of this diverse and interesting topic, I believe they provide an interesting and, I hope, illuminating snapshot of the exciting work that is being done in this field. I would like to extend my thanks and appreciation to all of the authors and reviewers for their contributions to this issue. I would also like to add that readers interested in this topic can search a new web resource that
524
Trends in Neurosciences October 2014, Vol. 37, No. 10
spotlights review content drawn from all Cell Press titles at: www.cell.com/reviews and they can discuss this topic and others on the Trends Facebook page at: www. facebook.com/trendscellpress. On a final note, I will be at the upcoming Society for Neuroscience conference in Washington DC next month, please stop by the Cell Press/Elsevier booth to chat and pick up a free copy of this special issue of TiNS, or stop me in a poster aisle or at a symposium, to let me know your thoughts on how the journal can best continue to offer engaging, accessible, and up-to-date content.
TiNS Special Issue: Circuit Development and Remodeling Andrew M. Clark Trends in Neurosciences, Cell Press, 600 Technology Square 5th Floor, Cambridge, MA 02139, USA
This month’s issue of Trends in Neurosciences focuses on the mechanisms underlying the construction and refinement of neural circuits, highlighting the important role that learning and injury, in addition to normal developmental processes, play in shaping both form and function in the juvenile and mature brain. Understanding circuit development and remodeling is important for formulating a more complete picture of both normal and pathological brain function, as circuits are considered to be a fundamental computational unit within the nervous system and circuit dysfunction is increasingly seen as central to many neurological and psychiatric diseases. During development, neural progenitor cells (NPCs) give rise to a myriad array of excitatory and inhibitory neurons and glia. Self-renewal, multipotency, and fate determination in NPCs is subject to a host of factors, including the action of the basic helix–loop–helix (bHLH) family of transcription factors. In this issue, Imayoshi and Kageyama review recent research into the effects of differential temporal expression of particular bHLH factors on fate determination, the versatile actions of particular bHLH factors on NPC function, and the structure of the bHLH signaling pathway. Excitatory–inhibitory (E–I) balance, the ratio of excitatory to inhibitory synaptic inputs to a given cell, is increasingly appreciated as a key determinant of network function, strongly affecting gain control at both the cellular and network level. Accumulating evidence suggests imbalances in E–I ratio exist in epilepsy and some forms of autism. In this issue, de Wit and Ghosh review work on the molecular organization of excitatory and inhibitory synapses, focusing on the role of leucine-rich repeat (LRR) proteins in coordinating synapse formation, differentiation, and plasticity. Proper routing of axons to their targets is essential for neural circuits to be wired correctly during development. This process is dependent upon a host of attractive and repulsive signals, and is central to appropriate function of local- and long-range circuits. In a Feature Review in this issue, Chedotal details the genetic and molecular mechanisms governing axon guidance in subsets of commissural neurons, cells whose axons cross the midline, in the brain and spinal cord that control and coordinate locomotion. For many years, conventional wisdom held that there are no new-born neurons in the juvenile and adult brain. Corresponding author: Clark, A.M. ([email protected]). 0166-2236/ ß 2014 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tins.2014.09.004
Now, it is widely acknowledged that neurogenesis does continue past development within several specialized zones in the mature brain. In these pages, Lim and Buylla discuss recent work examining the organization of neural stem cells (NSCs) in one of these niches, the so-called ventricular–subventricular zone (V–SVZ), which gives rise to various types of neurons that are eventually integrated into olfactory bulb circuits. Recent findings regarding neuronal production and the epigenetic mechanisms that maintain adult neurogenesis in the V–SVZ have the capacity to impact our understanding of neural development more broadly. Axonal degeneration occurs normally in development as initially broad and non-selective connectivity is shaped by experience. Axon loss is also a feature of injury and several diseases of the nervous system; thus, identifying mechanisms of axonal preservation and survival are important both for understanding neural development and developing methods for treating and preventing neurodegenerative disease. In this issue, Pease and Segal review recent research into the mechanisms underlying axonal survival in normal development and following insult or disease. Following insult, severed axons in the adult CNS have little capacity for regeneration, a fact that limits functional recovery following severe injury. In recent years, the mechanisms underlying this inhibition of axonal re-growth, as well as the mechanisms underlying post-injury sprouting and reorganization, have begun to yield to empirical investigation. In the pages of this issue, Chen and Zheng detail recent progress in this area, arguing that the days of therapeutic stimulation of directed circuit re-wiring are within reach. Not all new synaptic connections formed following injury are beneficial, as seen from work examining synaptic reorganization following retinal degeneration. Synaptic remodeling during development, or following injury or disease can be readily studied in the retina, due to its exquisite and well-understood organization and connectivity. Here, D’Orazi, Suzuki, and Wong review recent discoveries concerning the mechanisms which govern retinal circuit remodeling during development, and discuss how establishment of aberrant patterns of connectivity following damage or disease might limit retinal function. Finally, it is now well-appreciated that everyday experience is constantly sculpting and shaping neural circuits. Accumulating evidence suggests that connectivity In this issue, Caroni et al. outline recent work examining this process of dynamic circuit re-organization, via selective addition, validation and elimination of synapses, across molecular, cellular, and systems levels. Trends in Neurosciences, October 2014, Vol. 37, No. 10
523
Editorial Obviously, there is too much exciting work being done on the development and remodeling of neural circuits to cover the subject exhaustively in the pages of a single issue. Although the articles included here thus only represent a sampling of this diverse and interesting topic, I believe they provide an interesting and, I hope, illuminating snapshot of the exciting work that is being done in this field. I would like to extend my thanks and appreciation to all of the authors and reviewers for their contributions to this issue. I would also like to add that readers interested in this topic can search a new web resource that
524
Trends in Neurosciences October 2014, Vol. 37, No. 10
spotlights review content drawn from all Cell Press titles at: www.cell.com/reviews and they can discuss this topic and others on the Trends Facebook page at: www. facebook.com/trendscellpress. On a final note, I will be at the upcoming Society for Neuroscience conference in Washington DC next month, please stop by the Cell Press/Elsevier booth to chat and pick up a free copy of this special issue of TiNS, or stop me in a poster aisle or at a symposium, to let me know your thoughts on how the journal can best continue to offer engaging, accessible, and up-to-date content.