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Hebb's postulate provided a crucial framework to understand synaptic alterations underlying learning and memory. Hebb's theory proposed that neurons that fire together, also wire together, which provided the logical framework for the strengthening of synapses. Weakening of synapses was however addressed by "not being strengthened", and it was only later that the active decrease of synaptic strength was introduced through the discovery of long-term depression caused by low frequency stimulation of the presynaptic neuron. In 1994, it was found that the precise relative timing of pre and postynaptic spikes determined not only the magnitude, but also the direction of synaptic alterations when tw...
Fast inhibitory transmission exerts a powerful control on neuronal excitability and network oscillations thought to be associated with high cognitive functions. An alteration of inhibitory signaling is associated with major neurological and psychiatric disorders including epilepsy. Once released from presynaptic nerve terminals, GABA and glycine cross the synaptic cleft and bind to postsynaptic receptors localized in precise apposition to presynaptic release sites. The functional organization of inhibitory synapses consists in a dynamic process which relies on a number of highly specialized proteins that ensure the correct targeting, clustering, stabilization and subsequent fate of synaptic ...
A new perspective on brain function depends upon an understanding of the interaction and integration of excitation and inhibition. A recent surge in research activity focused on inhibitory interneurons now makes a more balanced view possible. Technological advances such as improved imaging methods, visualized patch-clamp recording, multiplex single-cell PCR, and gene-targeted deletion or knock-in mice are some of the novel tools featured in this book. This book will provide an integrated view of neuron function, operating in a balanced regime of excitation and inhibition. It is a timely contribution emphasizing how this balance is established, maintained, and modified from the molecular to system levels. The broad spectrum of topics from molecular to cellular and system/computational neuroscience will appeal to a wide audience of advanced graduate students, post-docs, and faculty. Moreover, this book this book features active young researchers from around the world, who are currently educating the brain scientists of tomorrow.
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...
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...
The first book to expose how the Catholic Church systematically covers up scandal by moving abusers across borders. Clerical sexual abuse is as global as the Roman Catholic Church, with bishops moving credibly accused priests not simply between parishes but also across international borders. Unforgivable follows the movement of one such perpetrator from the Great Plains of central Minnesota to the Indigenous highlands of Guatemala, where this priest had access to children and even raised one as his own. Although Father David Roney is at the center of this particular story, author Kevin Lewis O'Neill offers ample evidence that offshoring priests is a common practice. These maneuvers and the callous indifference of the Church--even once caught red-handed--reveal the limits of justice. They also lay bare the disturbing fact that the scale of clerical sexual abuse is far bigger than anyone has yet considered. Rigorously researched and viscerally important, this book raises urgent questions about holding the Catholic Church accountable.
The genetic, molecular, and cellular mechanisms of neural development are essential for understanding evolution and disorders of neural systems. Recent advances in genetic, molecular, and cell biological methods have generated a massive increase in new information, but there is a paucity of comprehensive and up-to-date syntheses, references, and historical perspectives on this important subject. The Comprehensive Developmental Neuroscience series is designed to fill this gap, offering the most thorough coverage of this field on the market today and addressing all aspects of how the nervous system and its components develop. Particular attention is paid to the effects of abnormal development ...
In the past several years, there has been an exciting body of new research that links impairments in the expression or function of neuronal chloride transporters to a growing number of diseases spanning from autism to brain aging. This book introduces the core concepts and highlights the recent advances in understanding the physiology and pathophysiology of the KCC and NKCC families of neuronal chloride transporters. Neuronal chloride transporter biology is reviewed, including roles in setting the transmembrane chloride gradient and the chloride transport-independent functions, such as regulating excitatory neurotransmission. Chapters are also dedicated to addressing the structure, post-tran...