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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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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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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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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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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