Astrocyte-neuron lactate transport is required for long-term memory formation

Akinobu Suzuki, Sarah A. Stern, Ozlem Bozdagi, George W. Huntley, Ruth H. Walker, Pierre J. Magistretti, Cristina M. Alberini

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)810-823
Number of pages14
JournalCell
Volume144
Issue number5
DOIs
StatePublished - Mar 4 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., & Alberini, C. M. (2011). Astrocyte-neuron lactate transport is required for long-term memory formation. Cell, 144(5), 810-823. https://doi.org/10.1016/j.cell.2011.02.018