Producing neuronal energy.

I wish to comment on the Report “Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis” by K. A. Kasischke et al. (2 July, p. 99) on energy metabolism involving interactions between neurons and astrocytes, and on the commentary to this paper, “Let there be (NADH) light” (L. Pellerin, P. J. Magistretti, Perspectives, 2 July, p. 50). Kasischke et al. present evidence for the coupling between oxidative metabolism in the dendritic shaft and glycolytic activity in the astrocyte to provide sustained neuronal energy in the form of adenosine triphosphate (ATP). The ATP produced by mitochondria in the dendritic shaft is presumed to travel into the dendritic spine, the site of the synapse, because there are no mitochondria in the spine. However, 7 years ago ([1][1]), another energy-producing system, forming ATP, was found to exist in the spine itself, produced by glycolytic enzymes localized in a structure called the postsynaptic density (PSD) at the postsynaptic membrane of the synapse. The significance of these findings is that the ATP generated at this important synapse site can be used at ion channels there, by various protein kinases there to phosphorylate proteins for signal transduction, and also for protein synthesis in the spine. Thus, there could exist two energy-producing systems, one existing in the astrocyte and in the dendritic shaft in the production of energy for general “housekeeping” metabolic functions, and the other at the postsynaptic PSD site for the processing of nerve signal transduction. With regards to the latter, the communication requirement of the central nervous system almost invites a specialized, localized, structural site for its most important mission. 1. 1.[↵][2]1. K. Wu, 2. C. Aoki, 3. A. Elste, 4. A. Rogalski-Wilk, 5. P. Siekevitz , Proc. Natl. Acad. Sci. U.S.A. 94, 13273 (1997). [OpenUrl][3][Abstract/FREE Full Text][4] # Response {#article-title-2} Siekevitz raises an interesting point, and we were well aware of his intriguing proposal of glycolytic generation of ATP in the dendritic spine during synaptic activity. It appears that according to his model, the temporal pattern of the presumed glycolytic response in the dendritic spine would have to closely, if not directly, follow the presynaptic input in order to meet metabolic needs induced by nerve signal conduction. In our experiments, we did not observe a rapid glycolytic burst. In contrast, the glycolytic response did not start until 10 s after stimulus onset and reached its peak after the cessation of the stimulus. However, our described experimental setup was not optimized to detect or locate a presumed brief transient glycolytic burst in the spine. We have shown that the activity-dependent glycolytic and oxidative metabolic responses in the central nervous system (CNS) are highly compartmentalized between astrocytes and neurons. It might indeed be intriguing to learn whether the (sub)cellular compartmentalization and specialization of the CNS is even more refined on a higher temporal and smaller spatial scale. [1]: #ref-1 [2]: #xref-ref-1-1 "View reference 1. in text" [3]: {openurl}?query=rft.jtitle%253DPNAS%26rft.stitle%253DProc.%2BNatl.%2BAcad.%2BSci.%2BUSA%26rft.aulast%253DWu%26rft.auinit1%253DK.%26rft.volume%253D94%26rft.issue%253D24%26rft.spage%253D13273%26rft.epage%253D13278%26rft.atitle%253DThe%2Bsynthesis%2Bof%2BATP%2Bby%2Bglycolytic%2Benzymes%2Bin%2Bthe%2Bpostsynaptic%2Bdensity%2Band%2Bthe%2Beffect%2Bof%2Bendogenously%2Bgenerated%2Bnitric%2Boxide%26rft_id%253Dinfo%253Adoi%252F10.1073%252Fpnas.94.24.13273%26rft_id%253Dinfo%253Apmid%252F9371836%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/ijlink/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czoxMToiOTQvMjQvMTMyNzMiO3M6NDoiYXRvbSI7czoyMjoiL3NjaS8zMDYvNTY5NS80MTAuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9