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.

The adult brain is not as hard-wired as traditionally thought. By modifying their small- or large-scale morphology, neurons can make new synaptic connections or break existing ones (structural plasticity). Structural changes accompany memory formation and learning, and are induced by neurogenesis, neurodegeneration and brain injury such as stroke. Exploring the role of structural plasticity in the brain can be greatly assisted by mathematical and computational models, as they enable us to bridge the gap between system-level dynamics and lower level cellular and molecular processes. However, most traditional neural network models have fixed neuronal morphologies and a static connectivity pattern, with plasticity merely arising from changes in the strength of existing synapses (synaptic plasticity). In The Rewiring Brain, the editors bring together for the first time contemporary modeling studies that investigate the implications of structural plasticity for brain function and pathology. Starting with an experimental background on structural plasticity in the adult brain, the book covers computational studies on homeostatic structural plasticity, the impact of structural plasticity on cognition and cortical connectivity, the interaction between synaptic and structural plasticity, neurogenesis-related structural plasticity, and structural plasticity in neurological disorders. Structural plasticity adds a whole new dimension to brain plasticity, and The Rewiring Brain shows how computational approaches may help to gain a better understanding of the full adaptive potential of the adult brain. The book is written for both computational and experimental neuroscientists. - Reviews the current state of knowledge of structural plasticity in the adult brain - Gives a comprehensive overview of computational studies on structural plasticity - Provides insights into the potential driving forces of structural plasticity and the functional implications of structural plasticity for learning and memory - Serves as inspiration for developing novel treatment strategies for stimulating functional repair after brain damage

Neurogenesis in the adult brain has emerged as one of the most dynamic and rapidly moving fields in modern neuroscience research. The implications of adult neurogenesis for health and well-being are wide-ranging, with findings in this area having distinct relevance for treatment and rehabilitation in neurology and psychopathology. Adult Neurogenesis in the Hippocampus addresses these implications by providing an up-to-date account on how neurogenesis in the adult hippocampus contributes to critical psychological and physiological processes, such as learning and memory, and how it is modified by life experiences, such as aging, environmental enrichment, exercise, and dieting. The book also provides the most current reviews of how adult hippocampal neurogenesis influences the pathogenesis of mood disorders, addiction, and key neurological disorders. This book is the ideal resource for researchers and advanced graduates seeking focused knowledge on the role of adult neurogenesis in brain health and disease. - Provides a unique overview of how adult hippocampal neurogenesis contributes to adaptive processes, brain psychopathology, and disease - Includes state-of-the-art reviews by leading world experts in adult neurogenesis

The CA3 hippocampal region receives information from the entorhinal cortex either directly from the perforant path or indirectly from the dentate gyrus via the mossy fibers (MFs). According to their specific targets (principal/mossy cells or interneurons), MFs terminate with large boutons or small filopodial extensions, respectively. MF-CA3 synapses are characterized by a low probability of release and pronounced frequency-dependent facilitation. In addition MF terminals are endowed with mGluRs that regulate their own release. We will describe the intrinsic membrane properties of pyramidal cells, which can sometimes fire in bursts, together with the geometry of their dendritic arborization. The single layer of pyramidal cells is quite distinct from the six-layered neocortical arrangement. The resulting aligned dendrites provides the substrate for laminated excitatory inputs. They also underlie a precise, diversity of inhibitory control which we will also describe in detail. The CA3 region has an especially rich internal connectivity, with recurrent excitatory and inhibitory loops. In recent years both in vivo and in vitro studies have allowed to better understand functional properties of the CA3 auto-associative network and its role in information processing. This circuit is implicated in encoding spatial representations and episodic memories. It generates physiological population synchronies, including gamma, theta and sharp-waves that are presumed to associate firing in selected assemblies of cells in different behavioral conditions. The CA3 region is susceptible to neurodegeneration during aging and after stresses such as infection or injury. Loss of some CA3 neurones has striking effects on mossy fiber inputs and can facilitate the generation of pathologic synchrony within the CA3 micro-circuit. 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.

Clinical musings on the nature of reality and “known experience.” Therapists must rely on their clients’ reporting of experience in order to assess, treat, and offer help. Yet we all experience the world through various filters of one sort or another, and our experiences are transformed through several nonconscious processes before reaching our conscious awareness. Science, philosophy, and wisdom traditions share the belief that our awareness is very restricted. How, then, can anyone accurately report their experience, let alone get help with it? Neuropsychologist Aldrich Chan examines how our experience of reality is assembled and shaped by biological, psychological, sociocultural, and existential processes. Each chapter explores processes within these domains that may act as “veils.” Topics in the book include: the default mode network, cognitive distortions, decision-making heuristics, the interconnected mind, memory, and cultural concepts of distress. By understanding the ways in which reality can be distorted, clinicians can more effectively help their clients reach their personal psychotherapeutic goals.

This is the 2nd edition of a very well received and popular book that reflects the current state-of-the-art of the ongoing research avenues concerning the hippocampus and processing units bridging the gap between single cell activity, network activity and global brain function. It aims to provide a methodology to anyone interested in developing microcircuit level models of the hippocampus. The book is divided into two thematic areas: (I) Experimental background and (II) Computational analysis. In part I, leading experimental neuroscientists discuss the morphological, physiological and molecular characteristics as well as the connectivity and synaptic properties of the various cell types found in the hippocampus. Behaviour-related ensemble activity patterns of morphologically identified neurons in anesthetized and freely moving animals provide insights on the function of the hippocampal areas. In part II, computational neuroscientists present models of the hippocampal microcircuits at various levels of detail (e.g. single cell level, network level, etc.). Synaptomics and connectomics models of hippocampal structures are initially discussed. Then, network models of memory, rhythm generation and spatial navigation are presented, followed by abstract and biophysical models of synaptic plasticity. Network models of hippocampal implicated disorders (epilepsy and schizophrenia) are then detailed and how their network topologies, connectivities and activities change in these diseases. Finally, two chapters are dedicated to describing simulator environments of single neurons and networks currently used by computational neuroscientists in developing their models and modelling tools to parametrically constrain them. This engaging volume is invaluable to experimental and computational neuroscientists, electrical engineers, physicists, mathematicians and others interested in developing microcircuit models of the hippocampus. Graduate level students and trainees in all of these fields can find this book a significant source of information.