Title | Astrocyte-neuron lactate transport is required for long-term memory formation. |
Publication Type | Journal Article |
Year of Publication | 2011 |
Authors | Suzuki, A, Stern, SA, Bozdagi, O, Huntley, GW, Walker, RH, Magistretti, PJ, Alberini, CM |
Journal | Cell |
Volume | 144 |
Issue | 5 |
Pagination | 810-23 |
Date Published | 2011 Mar 4 |
ISSN | 1097-4172 |
Keywords | Animals, Arabinose, Astrocytes, Glycogen, Hippocampus, Imino Furanoses, Lactic Acid, Memory, Long-Term, Monocarboxylic Acid Transporters, Muscle Proteins, Neurons, Rats, Sugar Alcohols, Symporters |
Abstract | We report that, in the rat hippocampus, learning leads to a significant increase in extracellular lactate levels that derive from glycogen, an energy reserve selectively localized in astrocytes. Astrocytic glycogen breakdown and lactate release are essential for long-term but not short-term memory formation, and for the maintenance of long-term potentiation (LTP) of synaptic strength elicited in vivo. Disrupting the expression of the astrocytic lactate transporters monocarboxylate transporter 4 (MCT4) or MCT1 causes amnesia, which, like LTP impairment, is rescued by L-lactate but not equicaloric glucose. Disrupting the expression of the neuronal lactate transporter MCT2 also leads to amnesia that is unaffected by either L-lactate or glucose, suggesting that lactate import into neurons is necessary for long-term memory. Glycogenolysis and astrocytic lactate transporters are also critical for the induction of molecular changes required for memory formation, including the induction of phospho-CREB, Arc, and phospho-cofilin. We conclude that astrocyte-neuron lactate transport is required for long-term memory formation. |
DOI | 10.1016/j.cell.2011.02.018 |
Alternate Journal | Cell |
PubMed ID | 21376239 |
PubMed Central ID | PMC3073831 |
Grant List | R01 MH065635 / MH / NIMH NIH HHS / United States R01 MH065635-07 / MH / NIMH NIH HHS / United States R01 MH065635-08 / MH / NIMH NIH HHS / United States R01 MH065635-09 / MH / NIMH NIH HHS / United States R01 MH065635-09S1 / MH / NIMH NIH HHS / United States R01 MH065635-10 / MH / NIMH NIH HHS / United States R01 MH074736 / MH / NIMH NIH HHS / United States R01 MH074736-03 / MH / NIMH NIH HHS / United States R01 MH074736-04 / MH / NIMH NIH HHS / United States R01 MH074736-05 / MH / NIMH NIH HHS / United States R01-MH065635 / MH / NIMH NIH HHS / United States R01-MH074736 / MH / NIMH NIH HHS / United States T32 MH087004 / MH / NIMH NIH HHS / United States T32-MH087004 / MH / NIMH NIH HHS / United States |
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