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The early postnatal period is a crucial stage for hippocampal development. During this critical period, the neonatal hippocampus is highly sensitive to the detrimental consequences of adverse environmental factors. Extensive clinical and preclinical evidence has shown that traumatic events early in life have profound and persistent effects on hippocampal function and behavior. This research topic focuses on the acute and lasting effects of early-life stress on various developmental processes in the hippocampus, and aims to uncover the molecules that are responsible for early-life stress-programmed effects and underlie resilience or vulnerability to stress-related neuropsychiatric disorders later in life. We hope the articles in this research topic will provide novel insights and stimulate future studies on the mechanisms of early-life stress and brain development.
early-life stress --- Hippocampus --- development --- plasticity --- molecular mechanism --- psychiatric disorders
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The hippocampus mediates several higher brain functions, such as learning, memory, and spatial coding. The input region of the hippocampus, the dentate gyrus, plays a critical role in these processes. Several lines of evidence suggest that the dentate gyrus acts as a preprocessor of incoming information, preparing it for subsequent processing in CA3. For example, the dentate gyrus converts input from the entorhinal cortex, where cells have multiple spatial fields, into the spatially more specific place cell activity characteristic of the CA3 region. Furthermore, the dentate gyrus is involved in pattern separation, transforming relatively similar input patterns into substantially different output patterns. Finally, the dentate gyrus produces a very sparse coding scheme in which only a very small fraction of neurons are active at any one time. How are these unique functions implemented at the level of cells and synapses? Dentate gyrus granule cells receive excitatory neuron input from the entorhinal cortex and send excitatory output to the hippocampal CA3 region via the mossy fibers. Furthermore, several types of GABAergic interneurons are present in this region, providing inhibitory control over granule cell activity via feedback and feedforward inhibition. Additionally, hilar mossy cells mediate an excitatory loop, receiving powerful input from a small number of granule cells and providing highly distributed excitatory output to a large number of granule cells. Finally, the dentate gyrus is one of the few brain regions exhibiting adult neurogenesis. Thus, new neurons are generated and functionally integrated throughout life. How these specific cellular and synaptic properties contribute to higher brain functions remains unclear. One way to understand these properties of the dentate gyrus is to try to integrate experimental data into models, following the famous Hopfield quote: "Build it, and you understand it." However, when trying this, one faces two major challenges. First, hard quantitative data about cellular properties, structural connectivity, and functional properties of synapses are lacking. Second, the number of individual neurons and synapses to be represented in the model is huge. For example, the dentate gyrus contains ~1 million granule cells in rodents, and ~10 million in humans. Thus, full scale models will be complex and computationally demanding. In this Frontiers Research Topic, we collect important information about cells, synapses, and microcircuit elements of the dentate gyrus. We have put together a combination of original research articles, review articles, and a methods article. We hope that the collected information will be useful for both experimentalists and modelers. We also hope that the papers will be interesting beyond the small world of "dentology", i.e., for scientists working on other brain areas. Ideally, the dentate gyrus may serve as a blueprint, helping neuroscientists to define strategies to analyze network organization of other brain regions.
Hippocampus --- Dentate Gyrus --- granule cells --- mossy cells --- mossy fibers --- mossy fiber synapses --- adult neurogenesis
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This Frontiers Research Topic on ‘Neural Circuits: Japan’ explores the diversity of neural circuit research occurring across Japan by innovative researchers using cutting-edge approaches. This issue has brought together papers revealing the development, structure, and physiology of neuronal circuits involved in sensory perception, sleep and wakefulness, behavioral selection, and motor command generation in a range of species from the nematode to the primate. Like the USA and Europe, Japan is now making a strong effort to elucidate neural circuit function in diverse organisms by taking advantages of optogenetics and innovative approaches for gene manipulation, traditional physiological and anatomical approaches, and neural pathway-selective inactivation techniques that have recently been developed in Japan.
Neocortex --- Hippocampus --- Olfactory Bulb --- Basal Ganglia --- Hypothalamus --- Cerebellum --- Drosophila --- C. elegans
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Coping has a myriad of facets: knowledge concerning the circumstances of threats to emotional and physical well being, the ability to meet immediate needs to mitigate, the potential for recurrence, the ability to apply efforts and resources to manage recurrence, and the complex assessment of competing motivations and changing circumstances. Successful coping is measured in the efficiency of efforts in balance with the degree of threat and likelihood of future occurrence. As one means of coping, avoidance encompass thoughts and efforts toward prevention of future aversive experiences and events. Anxiety disorders exemplify an extreme bias toward avoidance. A diathesis learning model focuses research efforts on individual vulnerabilities to acquire and express avoidance, the neurobiology of avoidance learning and its attendant circuitry. A fundamental understanding of avoidance through a diathesis learning model offers will facilitate the development of effective treatment protocols in alleviating anxiety disorders.
Anxiety --- posttraumatic stress disorder --- coping --- stress --- expectancy --- RDoC --- Diathesis --- cingulate --- Amygdala --- Hippocampus
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Glial cells are no longer considered passive bystanders in neuronal brain circuits. Not only are they required for housekeeping and brain metabolism, they are active participants in regulating the physiological function and plasticity of brain circuits and the online control of behavior both in invertebrate and vertebrate model systems. In invertebrates, glial cells are essential for normal function of sensory organs (C. elegans) and necessary for the circadian regulation of locomotor activity (D. melanogaster). In the mamallian brain, astrocytes are implicated in the regulation of cortical brain rhythms and sleep homeostasis. Disruption of AMPA receptor function in a subset of glial cell types in mice shows behavioral deficits. Furthermore, genetic disruption of glial cell function can directly control behavioral output. Regulation of ionic gradients by glia can underlie bistability of neurons and can modulate the fidelity of synaptic transmission. Grafting of human glial progenitor cells in mouse forebrain results in human glial chimeric mice with enhanced plasticity and improved behavioral performance, suggesting that astrocytes have evolved to cope with information processing in more complex brains. Taken together, current evidence is strongly suggestive that glial cells are essential contributors to information processing in the brain. This Research Topic compiles recent research that shows how the molecular mechanisms underlying glial cell function can be dissected, reviews their impact on plasticity and behavior across species and presents novel approaches to further probe their function.
glia --- Astrocytes --- plasticity --- Behavior --- Gq --- DREADD --- C. elegans --- Hippocampus --- Cerebellum --- Cortex
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It is in general well appreciated that the cortical interneurons play various important roles in cortical neuronal networks both in normal and pathological states. Based on connectivity pattern, developmental, morphological and electrophysiological properties, distinct subgroups of GABAergic interneurons can be differentiated in the neocortex as well as in the hippocampal formation. In this E-Book, we are focusing our attention on inhibitory interneurons expressing calcium-binding protein calretinin (CR). The aim of the E-Book is to consolidate the knowledge about this interneuronal population and to inspire further research on the function and malfunction of these neurons, which – functionally – seem to stand "at the top of the pyramid" of cortical interneuronal types.
calretinin --- Interneurons --- Cortical Circuits --- Cortical development --- GABA --- Calcium-Binding Proteins --- Epilepsy --- claustrum --- Hippocampus --- Neocortex
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The aim of this special topic is to bring together experts on the cellular and molecular mechanisms regulating the wiring properties of the CA3 hippocampal microcircuit in both physiological and pathological conditions, synaptic plasticity, behavior and cognition.We will particularly emphasize the dual glutamatergic and GABAergic phenotype of MF-CA3 synapses at early developmental stages and the steps that regulate the integration of newly generated neurons into the adult dentate gyrus-CA3 circuit.
Hippocampus --- CA3 subfield --- mossy fibers --- Associative network --- Theta Rhythm --- spatial representation --- episodic memory
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There is an assumption that environmental threats could cause important damages in central nervous system. As a consequence, several forms of brain structural plasticity could be affected. The environmentally mediated risks include generally physical (such as brain and spinal cord injury) and psychological / psychosocial influences (e.g. stress). In general, the response of the organism to these environmental challenges passes via adaptive responses to maintain homeostasis or functional recovery. These processes engage the immune system, the autonomic nervous system (ANS) besides the hypothalamo-hypophyseo-adrenal (HPA) axis via specific hormones, neurotransmitters, neuropeptides and other factors which participate, in several cases, in structural remodeling in particular brain areas. To what extent a brain and / or spinal cord recovery after structural and / or physiological / psychological damage could occur and by which mechanisms, this is the goal of this Research Topic. It concerns neurogenesis, growth factors and their receptors, and morphological plasticity. On the other hand, it is well known that stress experienced an obvious impact on many behavioral and physiological aspects. Thus, environmental stress affects neuroendocrine structure and function and hence such aspects may influence brain development. Knowing normal organization of neurotensin receptors’ system during postnatal development in human infant will help understanding the dysfunction of this neuropetidergic system in “sudden infant syndrome” victims. Stress could affect also other non-neuroendocrine regions and systems. GABA is one of the classical neurotransmitter sensitive to stress either when applied acutely or repetitively as well as its receptor GABAA. Furthermore, the modulation of this receptor complex notably by neurosteroids is also affected by acute stress. These steroids seem to play a role in the resilience retained by the stressed brain. Their modulatory role will be studied in the context of chronic stress in rats. Finally, one of the major impacts of stress besides changes in psychological behavior is the alteration of food intake control causing in final eating disorders. This alteration is the result of changes occurring in activity of brain regions involved in stress responses (principally HPA and ANS) and which are also involved in food intake control. The series of studies presented here, will try to explain how different stress paradigms affect this function and the eventual interactions of glucocorticoids with orexigenic (neuropetide Y: NPY/Agouti Related Peptide: AgRP) and anorexigenic peptides (Pre-opiomelanocortin peptide: POMC/Cocaine Amphetamine regulatory Transcript peptide: CART).
Neurotoxicity --- Stem Cells --- Neuroprotection --- neurological recovery --- Neurogenesis --- Hypothalamic regulation --- NO-producing cells --- Neurotensin --- Epilepsy --- hippocampus
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"Intrinsic Clocks" presents an array of current research activities on intrinsic clocks and their contributions to biology and physiology. It elucidates the current models for the intrinsic clocks, their molecular components and key mechanisms as well as the key brain regions and animal models for their behavioral analysis.It provides a timely view on how these clocks guide behavior, and how their disruption may cause depressive-like behavior and impairment in cognitive functions. Thereby, any specific method by which the mood-related functions of the intrinsic clocks might be influenced bears therapeutic potential and has clinical interest.The importance of some of these mechanisms was highlighted by the 2017 award of the Nobel Prize in Physiology or Medicine to Jeffrey C. Hall, Michael Rosbash, and Michael W. Young for their discoveries of the genetic control of the daily biological rhythm. The key to the explanation was the discovery of transcription-translation feedback loops of the so-called “clock genes.”
circadian --- cryptochrome --- diurnal --- hippocampus --- mood --- nocturnal --- oscillation --- seasonal --- small-molecule --- tanycytes
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Episodic memory refers to the ability to remember personal experiences in terms of what happened and where and when it happened. Humans are also able to remember the specific perceptions, emotions and thoughts they had during a particular experience. This highly sophisticated and unique memory system is extremely sensitive to cerebral aging, neurodegenerative and neuropsychiatric diseases. The field of episodic memory research is a continuously expanding and fascinating area that unites a broad spectrum of scientists who represent a variety of research disciplines including neurobiology, medicine, psychology and philosophy. Nevertheless, important questions still remain to be addressed. This research topic on the Progress in Episodic Memory Research covers past and current directions in research dedicated to the neurobiology, neuropathology, development, measurement and treatment of episodic memory.
episodic memory --- episodic-like memory --- mental time travel --- autobiographical memory --- non-declarative memory --- animal cognition --- Hippocampus --- Consciousness --- medial temporal lobe --- metacognition
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