Nature reviews. Neuroscience
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Nat. Rev. Neurosci. · May 2014
ReviewMicroglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease.
Mononuclear phagocytic cells in the CNS used to be defined according to their anatomical location and surface marker expression. Recently, this concept has been challenged by the results of developmental and gene expression profiling studies that have used novel molecular biological tools to unravel the origin of microglia and to define their role as specialized tissue macrophages with long lifespans. Here, we describe how these results have redefined microglia and helped us to understand how different myeloid cell populations operate in the CNS based on their cell-specific gene expression signatures, distinct ontogeny and differential functions. Moreover, we describe the vulnerability of microglia to dysfunction and propose that myelomonocytic cells might be used in the treatment of neurological and psychiatric disorders that are characterized by primary or secondary 'microgliopathy'.
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The neurotransmitters GABA and glycine mediate fast synaptic inhibition by activating ligand-gated chloride channels--namely, type A GABA (GABA(A)) and glycine receptors. Both types of receptors are anchored postsynaptically by gephyrin, which self-assembles into a scaffold and interacts with the cytoskeleton. ⋯ Moreover, post-translational modifications of gephyrin regulate the formation and plasticity of GABAergic synapses by altering the clustering properties of postsynaptic scaffolds and thereby the availability and function of receptors and other signalling molecules. Here, we discuss the formation and regulation of the gephyrin scaffold, its role in GABAergic and glycinergic synaptic function and the implications for the pathophysiology of brain disorders caused by abnormal inhibitory neurotransmission.
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Chemicals that are used experimentally to evoke itch elicit activity in diverse subpopulations of cutaneous pruriceptive neurons, all of which also respond to painful stimuli. However, itch is distinct from pain: it evokes different behaviours, such as scratching, and originates from the skin or certain mucosae but not from muscle, joints or viscera. New insights regarding the neurons that mediate the sensation of itch have been gained from experiments in which gene expression has been manipulated in different types of pruriceptive neurons as well as from comparisons between psychophysical measurements of itch and the neuronal discharges and other properties of peripheral and central pruriceptive neurons.