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Learning and memory are believed to depend on plastic changes of neuronal circuits due to activity-dependent potentiation or depression of specific synapses. During the last two decades, plasticity of brain circuits was hypothesized to mainly rely on the flexibility of glutamatergic excitatory synapses, whereas inhibitory synapses were assumed relatively invariant, to ensure stable and reliable control of the neuronal network. As a consequence, while considerable efforts were made to clarify the main mechanisms underlying plasticity at excitatory synapses, the study of the cellular/molecular mechanisms of inhibitory plasticity has received much less attention. Nevertheless, an increasing bod...
Several types of brain injuries are causes of acquired temporal lobe epilepsy (TLE). The seizure-free "latent period" that often follows the brain injury is of unknown mechanistic significance but is commonly considered as the "epileptogenic" period characterized by gradual pathogenic processes leading to the onset of clinically detectable epilepsy. Acute convulsive status epilepticus (SE) is often associated with an adverse developmental outcome characterized by learning disabilities related to the cumulative effects of seizures and development of TLE. The symptomatic manifestations of TLE appear only after a widespread irreversible damage of entorhinal cortex, and hippocampus, the brain ar...
This volume is based on an advanced course on epileptogenic and excitotoxic mechanisms with emphasis on development. Information on partial and generalized epileptogenesis, derived from different experimental models, is comprehensively reviewed. Special sections are devoted to anatomical, biochemical and functional aspects of the maturing brain and to their interaction with epileptogenic agents.
GABAergic neurons provide most of the inhibitory drive of adult networks and play major roles in the integrative properties of brain networks. Alterations of GABAergic signals are associated with major neurological disorders and GABA mimetic drugs are widely used as comfort molecules and to treat several brain disorders. Thus, the inhibitory drive is altered in epilepsies, infantile developmentally related disorders but also Parkinson disease, and anoxo-ischemic insults to just name a few. From the developmental stand point, GABAergic neurons mature before principal neurons and provide an important source of early activities and are thus instrumental in activity dependent modulation of the c...
Stroke remains one of the most devastating diseases in industrialized countries. Recanalization of the occluded arterial vessel using thrombolysis is the only causal therapy available. However, thrombolysis is limited due to severe side effects and a limited time window. As such, only a minority of patients receives this kind of therapy, showing a need for new and innovative treatment strategies. Although neuroprotective drugs have been shown to be beneficial in a variety of experimental stroke models, they ultimately failed in clinical trials. Consequently, recent scientific focus has been put on modulation of post-ischemic neuroregeneration, either via stimulation of endogenous neurogenesi...
Autism spectrum disorders (ASDs) are a group of genetically and clinically heterogeneous neurodevelopmental disorders characterized by impaired reciprocal social interactions and communication, and restricted and repetitive patterns of behaviors and interests. Studies in genetics, neurobiology and systems biology are providing insights into the pathogenesis of ASDs. Investigation of neural and synaptic defects in ASDs not only sheds light on the molecular and cellular mechanisms that govern the function of the central nervous system, but may lead to the discovery of potential therapeutic targets for autism and other cognitive disorders. Our Research Topic which constitutes this e-book documents the recent development and ideas in the study of pathogenesis and treatment of ASDs, with an emphasis on syndromic disorders such as fragile X and Rett syndromes. In addition, model systems and methodological approaches with translational relevance to autism are covered herein. We hope that the Research Topic will enhance the global knowledge base in the autism research community and foster new research directions in autism related biology.
This volume critically examines the functional actions of the kainate‐type glutamate receptors (KARs). Following on from the larger body of work on the NMDA‐ and AMPA-type ionotropic glutamate receptors (GluRs), studies with KARs have consistently thrown up exceptions to general rules about synaptic modulation. Contributors herein provide an insight to the idiosyncracies that now almost typify the KAR field. The fascinating insights provided in this volume serve to encourage searching mechanistic questions.
A new phase of anti-epileptic drugs (AEDs) investigation has begun in which new drugs can be designed to target specific epileptogenic mechanisms. A rational approach to therapy today requires not only a full awareness of phamacokinetics of AEDs but also a thorough knowledge of their molecular targets and of their influence on excitatory and inhibitory mechanisms in the brain. This book provides a multi-author systematic look at this subject, from neurobiological bases to clinical applications. It includes four sections dealing with fundamental aspects of cortical excitability, models of epileptic disorders, targets for anti-epileptic drugs and rational approaches to therapy. Each chapter provides a review of a specific topic prepared by well known scientists active in the field, introducing their most recent results in a concise and comprehensive form.
The understanding of parallel processing and of the mechanisms underlying neural networks in the brain is certainly one of the most challenging problems of contemporary science. During the last decades significant progress has been made by the combination of different techniques, which have elucidated properties at a cellular and molecular level. However, in order to make significant progress in this field, it is necessary to gather more direct experimental data on the parallel processing occurring in the nervous system. Indeed the nervous system overcomes the limitations of its elementary components by employing a massive degree of parallelism, through the extremely rich set of synaptic int...
Autism is an extremely complex neurodevelopmental disorder that is expressed in a spectrum of phenotypes and is characterised by impaired reciprocal social communication and stereotyped patterns of interests and activities. Its aetiopathogenesis remains poorly understood. This exhaustive synthesis discusses various aspects: A focus on the neurobiology of autism: the candidate genes implicate an involvement of numerous brain regions and a concomitant malfunctioning of neurotransmitter, immunologic, and other mechanisms; The most incisive rehabilitation models in their original formulation and the results achieved with the same or similar protocols in Italian centres (understanding, language therapy, social skill training; The psychopharmacologic options for the condition of autism per se and for its associated, very frequent, comorbidities. It suggests a potential influence on professional practice and enables an up-to-date approach to effective diagnosis and treatment.