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

Cell. 2011 Mar 4;144(5):810-23. doi: 10.1016/j.cell.2011.02.018.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arabinose
  • Astrocytes / metabolism*
  • Glycogen / metabolism
  • Hippocampus / metabolism
  • Imino Furanoses
  • Lactic Acid / metabolism*
  • Memory, Long-Term* / drug effects
  • Monocarboxylic Acid Transporters / metabolism*
  • Muscle Proteins / metabolism
  • Neurons / metabolism*
  • Rats
  • Sugar Alcohols / pharmacology
  • Symporters / metabolism


  • Imino Furanoses
  • Monocarboxylic Acid Transporters
  • Muscle Proteins
  • Slc16a4 protein, mouse
  • Sugar Alcohols
  • Symporters
  • monocarboxylate transport protein 1
  • 1,4-dideoxy-1,4-iminoarabinitol
  • Lactic Acid
  • Glycogen
  • Arabinose