Structure Function And Plasticity Of Hippocampal Dentate Gyrus Microcircuits

Structure, function, and plasticity of hippocampal dentate gyrus microcircuits

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.

Structure, Function, and Plasticity of Hippocampal Dentate Gyrus Microcircuits

The Rewiring Brain

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