Trends in neurosciences
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Endogenous neurosteroids and their synthetic analogs (neuroactive steroids) are potent modulators of GABA(A) receptors. Thus, they are of physiological and clinical relevance for their ability to modulate inhibitory function in the CNS. Despite their importance, fundamental issues of neurosteroid actions remain unresolved. ⋯ Other recent studies have identified putative neurosteroid binding sites on GABA(A) receptors. In this Opinion, we argue that neurosteroids require a membranous route of access to transmembrane-domain binding sites within GABA(A) receptors. This has implications for the design of future neuroactive steroids because the lipid solubility and related accessibility properties of the ligand are likely to be key determinants of receptor modulation.
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Trends in neurosciences · Aug 2009
ReviewTripartite synapses: astrocytes process and control synaptic information.
The term 'tripartite synapse' refers to a concept in synaptic physiology based on the demonstration of the existence of bidirectional communication between astrocytes and neurons. Consistent with this concept, in addition to the classic 'bipartite' information flow between the pre- and postsynaptic neurons, astrocytes exchange information with the synaptic neuronal elements, responding to synaptic activity and, in turn, regulating synaptic transmission. Because recent evidence has demonstrated that astrocytes integrate and process synaptic information and control synaptic transmission and plasticity, astrocytes, being active partners in synaptic function, are cellular elements involved in the processing, transfer and storage of information by the nervous system. Consequently, in contrast to the classically accepted paradigm that brain function results exclusively from neuronal activity, there is an emerging view, which we review herein, in which brain function actually arises from the coordinated activity of a network comprising both neurons and glia.
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Trends in neurosciences · Jul 2009
ReviewNucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling.
In neurons multiple signaling pathways converge in the nucleus to regulate the expression of genes associated with long-term structural changes of synapto-dendritic input. Of pivotal importance for this type of transcriptional regulation is synapse-to-nucleus communication. ⋯ We discuss the mechanisms involved in their translocation and their role in the control of nuclear gene expression. Finally, we summarize the current thinking regarding the functional implications of nuclear signaling and address open questions in this evolving area of neuroscience.
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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.