The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
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Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a "small adult brain." One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride concentration [Cl(-)](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl(-)](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. ⋯ Here, the authors stress the importance of determining how [Cl(-)](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical perspective, agents that control [Cl(-)](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders.
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Autophagy is a cellular mechanism for degrading proteins and organelles. It was first described as a physiological process essential for cellular health and survival, and this is its role in most cells. ⋯ The authors here discuss these distinct roles of autophagy in the nervous system with a focus on the role of autophagy in mediating neuronal death. The development of new therapeutic strategies based on the manipulation of autophagy will need to take into account these opposing roles of autophagy.
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Nociceptive stimuli are transmitted through thinly myelinated or unmyelinated primary afferent fibers called nociceptors, which terminate mainly in the superficial dorsal horn of the spinal cord. While most nociceptive fibers terminate in the spinal segment of the entrance, (collateral) fibers may ascend and descend several segments upon their entry into the spinal cord, which is reflected in the receptive fields of central nociceptive neurons. ⋯ While anatomical, physiological, and psychophysical techniques have focused on one particular aspect of central sensitization at a time, functional imaging techniques like functional MRI, intrinsic optical imaging, and autofluorescent flavoprotein imaging (AFI) are able to capture both spatial and temporal dimensions of central sensitization simultaneously. AFI and other neuroimaging techniques may clarify fundamental aspects relating to the spread of nociceptive activity within the spinal cord and may thus provide a practical tool to test the efficacy of new analgesic drugs or procedures in animals and ultimately in humans.
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Recent advances in chromatin biology have identified a role for epigenetic mechanisms in the regulation of neuronal gene expression changes, a necessary process for proper synaptic plasticity and memory formation. Experimental evidence for dynamic chromatin remodeling influencing gene transcription in postmitotic neurons grew from initial reports describing posttranslational modifications of histones, including phosphorylation and acetylation occurring in various brain regions during memory consolidation. ⋯ This present review examines learning-induced gene transcription by chromatin remodeling underlying long-lasting changes in neurons, with direct implications for the study of epigenetic mechanisms in long-term memory formation and behavior. Furthermore, the study of epigenetic gene regulation, in conjunction with transcription factor activation, can provide complementary lines of evidence to further understanding transcriptional mechanisms subserving memory storage.
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Neuroimaging allows researchers and clinicians to noninvasively assess structure and function of the brain. With the advances of imaging modalities such as magnetic resonance, nuclear, and optical imaging; the design of target-specific probes; and/or the introduction of reporter gene assays, these technologies are now capable of visualizing cellular and molecular processes in vivo. Undoubtedly, the system biological character of molecular neuroimaging, which allows for the study of molecular events in the intact organism, will enhance our understanding of physiology and pathophysiology of the brain and improve our ability to diagnose and treat diseases more specifically. ⋯ Today, molecular neuroimaging is still an experimental approach with limited clinical impact; this is expected to change within the next decade. This article provides an overview of molecular neuroimaging approaches with a focus on rodent studies documenting the exploratory state of the field. Concepts are illustrated by discussing applications related to the pathophysiology of Alzheimer's disease.