Trends in neurosciences
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Trends in neurosciences · Jul 2008
ReviewCholinergic control of GABA release: emerging parallels between neocortex and hippocampus.
Release of acetylcholine (ACh) into the neocortex and hippocampus profoundly alters cellular excitability, network synchronization and behavioral state. Despite its diverse cellular and synaptic targets, the actions of ACh can be highly specific, altering the excitability of distinct inhibitory and excitatory cell types. This review presents evidence for the selectivity of cholinergic neuromodulation in GABAergic interneurons and identifies emerging parallels between the neocortex and hippocampus. In light of growing evidence that neuromodulatory specializations relate to neurochemical identity, I propose that differential engagement of neurochemically distinct interneuron subtypes is a unifying principle by which ACh orchestrates the flow of sensory information in the neocortex and hippocampus.
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Gephyrin is a multifunctional protein responsible for molybdenum cofactor synthesis and the clustering of glycine and GABA(A) receptors at inhibitory synapses. Based on the structure of its two conserved domains, G and E, gephyrin is thought to form a hexagonal lattice serving as a scaffold for accessory proteins at postsynaptic sites. ⋯ Here we review the current state of knowledge about gephyrin, highlighting new research avenues based on a different structural model and a revised nomenclature for gephyrin splice variants. Unraveling the biology of gephyrin will further our understanding of glycinergic and GABAergic synapses in health and disease.
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Investigation of the basic mechanisms of chronic pain not only provides insights into how the brain processes and modulates sensory information but also provides the basis for designing novel treatments for currently intractable clinical conditions. Human brain imaging studies have revealed new roles of cortical neuronal networks in chronic pain, including its unpleasant quality, and mouse studies have provided molecular and synaptic mechanisms underlying relevant cortical plasticity. This review paper will critically examine the current literature and propose a cortical network model for chronic pain.
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Gain-of-function mutations or dysregulated expression of voltage-gated sodium channels can produce neuronal hyperexcitability, leading to acute or chronic pain. The sodium channel Na(v)1.7 is expressed preferentially in most slowly conducting nociceptive neurons and in sympathetic neurons. Gain-of-function mutations in the Na(v)1.7 channel lead to DRG neuron hyperexcitability associated with severe pain, whereas loss of the Na(v)1.7 channel in patients leads to indifference to pain. The contribution of Na(v)1.7 to acquired and inherited pain states and the absence of motor, cognitive and cardiac deficits in patients lacking this channel make it an attractive target for the treatment of neuropathic pain.