Brain’s enormous energy consumption (something I have dubbed the brain

Brain’s enormous energy consumption (something I have dubbed the brain’s dark energy [6,7]1) is little affected by task performance, an observation first made more than 50 years ago by Louis Sokoloff, Seymour Kety and their colleagues [8] but rarely cited (see also [4] for an interesting evolutionary perspective). What is the nature of this ongoing intrinsic activity that commands such a large amount of the brain’s energy resources? Assessments of brain energy budget using a variety of approaches (for review, see [5]) would suggest that 60?80 of overall brain energy consumption is devoted to spike-generated glutamate cycling and, hence, neural signalling processes involving principal cells. The basis for this estimate, however, should be viewed with caution for several reasons. First, it is important to realize that most of the ongoing electrical activity of the neocortex is, in fact, subthreshold depolarizations rather than action potential firing ([9], see also [10]). Second, early estimates of the cost of spikes fell far short of explaining the cost of brain function [11]. Also, current estimates leave for future consideration the demands placed on the brain’s energy budget by the activity of inhibitory interneurons [12?17], astrocytes [18,19] and other supporting cells [20]. Furthermore, it is important to emphasize that biosynthesis may be a significant contributor to the cost of brain function [21]. Eve Marder has described the situation nicely [22, p. 563]: `Humans and other long-lived animals . . . have neurons that live and function for decades. By contrast, ion channel proteins, synaptic receptors and the components of signal transduction pathways are constantly turning over in the membrane and being replaced, with half-lives of minutes, hours, days or weeks. Therefore, each neuron is constantly rebuilding itself from its constituent proteins, using all of the molecular and biochemical machinery of the cell. This allows for plastic changes in development and learning but also poses the problem of how stable neuronal function is maintained . . . ‘ As Locasale Cantley [21] have pointed out, basal cellular maintenance of the type Eve Marder describes is very costly, something probably underestimated [23]. This is a subject to which I will return later in this essay (see Intrinsic activity and metabolism).Phil. Trans. R. Soc. B 370:3. The organization of intrinsic activityImportant insights into the organization of intrinsic activity have come from two perspectives: a top?down approach using brain imaging with PET and fMRI as well as genetics in normal humans and electrocorticography in selected patients; and a bottom p approach using laboratory animals and more invasive, high-resolution (spatial and temporal) studies employing neurophysiological as well as optical imaging techniques. Together a picture of the dynamic organization of intrinsic activity emerges that is remarkably complementary across these levels of analysis.(a) Top own view: activity decreases from a resting stateBy the early 1980s, PET began to receive serious attention as a potential functional NS-018MedChemExpress NS-018 neuroimaging device in human subjects [32]. The study of human cognition with neuroimaging was aided greatly by the involvement of cognitive psychologists in the 1980s whose experimental strategies for dissecting human behaviours fitted well with the emerging capabilities of functional brain imaging [33]. This strategy, involving the purchase CP 472295 careful selection of task and con.Brain’s enormous energy consumption (something I have dubbed the brain’s dark energy [6,7]1) is little affected by task performance, an observation first made more than 50 years ago by Louis Sokoloff, Seymour Kety and their colleagues [8] but rarely cited (see also [4] for an interesting evolutionary perspective). What is the nature of this ongoing intrinsic activity that commands such a large amount of the brain’s energy resources? Assessments of brain energy budget using a variety of approaches (for review, see [5]) would suggest that 60?80 of overall brain energy consumption is devoted to spike-generated glutamate cycling and, hence, neural signalling processes involving principal cells. The basis for this estimate, however, should be viewed with caution for several reasons. First, it is important to realize that most of the ongoing electrical activity of the neocortex is, in fact, subthreshold depolarizations rather than action potential firing ([9], see also [10]). Second, early estimates of the cost of spikes fell far short of explaining the cost of brain function [11]. Also, current estimates leave for future consideration the demands placed on the brain’s energy budget by the activity of inhibitory interneurons [12?17], astrocytes [18,19] and other supporting cells [20]. Furthermore, it is important to emphasize that biosynthesis may be a significant contributor to the cost of brain function [21]. Eve Marder has described the situation nicely [22, p. 563]: `Humans and other long-lived animals . . . have neurons that live and function for decades. By contrast, ion channel proteins, synaptic receptors and the components of signal transduction pathways are constantly turning over in the membrane and being replaced, with half-lives of minutes, hours, days or weeks. Therefore, each neuron is constantly rebuilding itself from its constituent proteins, using all of the molecular and biochemical machinery of the cell. This allows for plastic changes in development and learning but also poses the problem of how stable neuronal function is maintained . . . ‘ As Locasale Cantley [21] have pointed out, basal cellular maintenance of the type Eve Marder describes is very costly, something probably underestimated [23]. This is a subject to which I will return later in this essay (see Intrinsic activity and metabolism).Phil. Trans. R. Soc. B 370:3. The organization of intrinsic activityImportant insights into the organization of intrinsic activity have come from two perspectives: a top?down approach using brain imaging with PET and fMRI as well as genetics in normal humans and electrocorticography in selected patients; and a bottom p approach using laboratory animals and more invasive, high-resolution (spatial and temporal) studies employing neurophysiological as well as optical imaging techniques. Together a picture of the dynamic organization of intrinsic activity emerges that is remarkably complementary across these levels of analysis.(a) Top own view: activity decreases from a resting stateBy the early 1980s, PET began to receive serious attention as a potential functional neuroimaging device in human subjects [32]. The study of human cognition with neuroimaging was aided greatly by the involvement of cognitive psychologists in the 1980s whose experimental strategies for dissecting human behaviours fitted well with the emerging capabilities of functional brain imaging [33]. This strategy, involving the careful selection of task and con.

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