Lactate from astrocytes fuels learning-induced mRNA translation in excitatory and inhibitory neurons

Commun Biol. 2019 Jul 2;2:247. doi: 10.1038/s42003-019-0495-2. eCollection 2019.

Abstract

Glycogenolysis and lactate transport from astrocytes to neurons is required for long-term memory formation, but the role of this lactate is poorly understood. Here we show that the Krebs cycle substrates pyruvate and ketone body B3HB can functionally replace lactate in rescuing memory impairment caused by inhibition of glycogenolysis or expression knockdown of glia monocarboxylate transporters (MCTs) 1 and 4 in the dorsal hippocampus of rats. In contrast, either metabolite is unable to rescue memory impairment produced by expression knockdown of MCT2, which is selectively expressed by neurons, indicating that a critical role of astrocytic lactate is to provide energy for neuronal responses required for long-term memory. These responses include learning-induced mRNA translation in both excitatory and inhibitory neurons, as well as expression of Arc/Arg3.1. Thus, astrocytic lactate acts as an energy substrate to fuel learning-induced de novo neuronal translation critical for long-term memory.

Keywords: Astrocyte; Consolidation; Learning and memory; Neuroscience.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / metabolism*
  • Avoidance Learning
  • Brain / metabolism
  • Citric Acid Cycle
  • Gangliosides
  • Glycogenolysis
  • Hippocampus / metabolism
  • Lactic Acid / metabolism*
  • Male
  • Memory Consolidation*
  • Memory Disorders / metabolism
  • Memory, Episodic
  • Monocarboxylic Acid Transporters / genetics
  • Neurons / metabolism*
  • Pyruvic Acid / metabolism
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Long-Evans

Substances

  • Gangliosides
  • Monocarboxylic Acid Transporters
  • RNA, Messenger
  • sialyl dimeric Le(X) glycononaosyl ceramide
  • Lactic Acid
  • Pyruvic Acid