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Cortical neurons in neurovascular and neurometabolic coupling| old_uid | 9382 |
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| title | Cortical neurons in neurovascular and neurometabolic coupling |
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| start_date | 2010/12/08 |
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| schedule | 11h |
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| online | no |
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| summary | Tight coupling between neuronal activity, local cerebral blood flow and metabolism is at the basis of contemporary brain imaging techniques, largely used to infer neuronal activity in health and disease. In the cerebral cortex, the hemodynamic response triggered by neuronal activity involves the release of various vasoactive messengers synthesized and released by different cell types including neurons and astrocytes. These hemodynamic changes are followed by a transient rise in lactate flux, extracellular glucose levels remaining fairly constant. Despite this physiopathological importance the cellular and molecular mechanisms, or even the functional consequences, of neurovascular and neurometabolic coupling are poorly understood. Several Glutamatergic and GABAergic neurons produce vasodilatory and/or vasoconstricting substances and are likely to account, at least partially, for the complex spatiotemporal hemodynamic response. However the large diversity of cortical neurons in the cerebral cortex makes it difficult to study their function(s) in neurovascular coupling. We sought to classify systematically cortical neurons allowing us to identify and to characterize different neuronal types potentially involved in neurovascular coupling. We showed that the activation of some of these neuronal types evoked vascular responses. These vasomotor neurons were dilating if they expressed type 2 cyclo-oxygenase, VIP or nNOS and constricting if they expressed somatostatin or NPY. To evaluate further the physiological consequences of changes in energy supply, we studied the influence of metabolic environments on neuronal activity, focusing on ATP sensitive K+ (KATP) channels. By coupling energy states with membrane potential these hyperpolarizing channels act as metabolic sensors. We observed that the vast majority of cortical neurons expressed functional KATP channels composed of Kir6.2 and SUR1 subunits. Using perforated patch recordings, which preserve intracellular metabolism, we found that an increased energy supply via glucose had little or no effect on neuronal activity. In contrast, increased energy supply via lactate doubled the evoked firing rate of neurons. We demonstrated that lactate-sensing in cortical neurons was mediated by lactate uptake and KATP channel closure. These results indicate that under physiological conditions cortical neurons prefer to metabolize lactate. The lactate-sensing of cortical neurons also suggests that negative feedback mechanisms might be recruited to prevent an explosive enhancement of neuronal activity by lactate supply. |
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| responsibles | Fabre-Thorpe |
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