Astrocyte-neuron lactate transport is required for long-term memory formation |
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Authors: | Suzuki Akinobu Stern Sarah A Bozdagi Ozlem Huntley George W Walker Ruth H Magistretti Pierre J Alberini Cristina M |
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Institution: | 1 Department of Neuroscience, Mount Sinai School of Medicine, New York, New York 10029 2 Department of Psychiatry, Mount Sinai School of Medicine, New York, New York 10029 3 Department of Neurology, James J. Peters VAMC, Bronx, NY 10468 4 Department of Neurology, Mount Sinai School of Medicine, New York, New York 10029 5 Laboratory of Neuroenergetics and Cellular Dynamics, Brain Mind Institute, Ecole Polytechnique Fédérale de Lausanne (EPFL) and Center for Psychiatric Neuroscience, University of Lausanne-CHUV, Lausanne, Switzerland |
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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. |
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