Layer- and area-specific actions of norepinephrine on cortical synaptic transmission
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The cerebral cortex is a critical target of the central noradrenergic system. The importance of norepinephrine (NE) in the regulation of cortical activity is underscored by clinical findings that involve this catecholamine and its receptor subtypes in the regulation of a large number of emotional and cognitive functions and illnesses. In this review, we highlight diverse effects of the LC/NE system in the mammalian cortex. Indeed, electrophysiological, pharmacological, and behavioral studies in the last few decades reveal that NE elicits a mixed repertoire of excitatory, inhibitory, and biphasic effects on the firing activity and transmitter release of cortical neurons. At the intrinsic cellular level, NE can produce a series of effects similar to those elicited by other monoamines or acetylcholine, associated with systemic arousal. At the synaptic level, NE induces numerous acute changes in synaptic function, and 'gates' the induction of long-term plasticity of glutamatergic synapses, consisting in an enhancement of engaged and relevant cortical synapses and/or depression of unengaged synapses. Equally important in shaping cortical function, in many cortical areas NE promotes a characteristic, most often reversible, increase in the gain of local inhibitory synapses, whose extent and temporal properties vary between different areas and sometimes even between cortical layers of the same area. While we are still a long way from a comprehensive theory of the function of the LC/NE system, its cellular, synaptic, and plastic effects are consistent with the hypothesis that noradrenergic modulation is critical in coordinating the activity of cortical and subcortical circuits for the integration of sensory activity and working memory. This article is part of a Special Issue entitled SI: Noradrenergic System. © 2016 Elsevier B.V.
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Abbreviations α-AR alpha adrenoceptor; ACC anterior cingulate cortex; ACh acetylcholine; AHP after hyper polarization current; AMPA amino propionic acid; AMPAR amino propionic acid sensitive receptor; CaMKII Calcium calmodulin kinase type 2; cAMP cyclic adenosine monophosphate; CNS Central Nervous System; CREB cAMP Response Element Binding protein; G-protein GTP-binding protein; GABA γ amino-butyric acid; GABAAR GABA receptor type A; GluR glutamate receptor; GTP guanosine 3-phosphate; HCN hyperpolarization activated cyclic nucleotide gated (cation channel); HPA Hypothalamus-Pituitary-Adrenal gland (axis); LC Locus Ceruleus; LTD long-term depression; LTP long-term potentiation; mPFC medial PFC; NE norepinephrine; NMDA N-methyl D aspartate; NMDAR NMDA receptor; OFC orbitofrontal cortex; PFC prefrontal cortex; PFC Prefrontal cortex; PKA protein kinase A; PKC protein kinase C; PLC phospholipase C; PLC phospholipase C; S/N signal-to-noise ratio; sAHP slow AHP; STDP spike-time dependent plasticity; TREK two-pore domain K+ (channel); β-AR beta adrenoceptor 4 aminobutyric acid; acetylcholine; adrenergic receptor; alpha 1 adrenergic receptor; beta adrenergic receptor; calcium; glutamic acid; monoamine; n methyl dextro aspartic acid receptor; noradrenalin; noradrenalin; adrenergic activity; anesthesia induction; arousal; brain cell; brain cortex; brain electrophysiology; cognition; depression; human; in vivo study; intrinsic activity; locus ceruleus; long term care; mammal; neocortex; nerve cell plasticity; nerve stimulation; neuromodulation; neurotransmitter release; nonhuman; noradrenergic nerve; prefrontal cortex; priority journal; Review; sensory gating; signal transduction; synaptic membrane; synaptic transmission; therapy effect; working memory; anatomy and histology; animal; brain cortex; cytology; metabolism; nerve cell; physiology; synaptic transmission; Animals; Cerebral Cortex; Humans; Neurons; Norepinephrine; Synaptic Transmission
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