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

By Akinobu Suzuki, Sarah A. Stern, O. Bozdagi, G. W. Huntley, R. Walker, Pierre J. Magistretti, C. Alberini. Cell, 2011

1,591 citations recorded by the source corpus.

SUMMARY We report that in the rat hippocampus learning leads to a significant increase in extracellular lactate levels, which 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 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.

Subfields: Biochemistry, Cellular and Molecular Neuroscience, Developmental Neuroscience

View Paper: https://www.semanticscholar.org/paper/4ac3cf43610451d7a0b34e8b7eb053fc09cf3a3d

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Citations in the corpus

Sugar for the brain: the role of glucose in physiological and pathological brain function (2013, background): “The notions that glycogen-derived lactate is necessary as the bioenergetic basis for neuronal memory consolidation [7, 32] and that glucose-derived lactate from oligodendrocytes is required to support axons [33, 34] demand direct experimental proof of the magnitude and contribution of lactate shuttl”
Synaptic energy use and supply. (2012, positive): “In addition, long-term potentiation and memory are disrupted by deletion of lactate transporters (Suzuki et al., 2011; Newman et al., 2011), but it is unclear whether this reflects an energetic or a signaling function of lactate (see above).”
Presynaptic stochasticity improves energy efficiency and helps alleviate the stability-plasticity dilemma (2021, background): “Firstly, there is evidence that memory formation requires energy (Morris et al., 2010; Suzuki et al., 2011; Hebert-Chatelain et al., 2016; Alberini et al., 2018).”
Astrocytes: a central element in neurological diseases (2016, background): “Insults to the CNS, regardless of their aetiology, strain the organ homeostasis and these are astrocytes, which, through dedicated molecular cascades, protect neurones against glutamate excitotoxicity, extracellular K+ overload, reactive oxygen species, and these are also astrocytes that supply stre”
Physiology of Astroglia. (2018, positive): “Glycogenolysis is also critically important for maintenance of LTP (1706) and for memory consolidation (573).”
Sweet Sixteen for ANLS (2012, background): “…the behavioral effects observed, the in vivo induction of long-term potentiation and of genes know to be required for memory formation such as phospho-CREB, Arc and phospho-cofilin is prevented by inhibition of glycogenolysis and MCT4 expression in a lactate-reversible manner (Suzuki et al, 2011).”
Brain metabolism in health, aging, and neurodegeneration (2017, positive): “Furthermore, pharmacological inhibition or genetic targeting of MCT2 irreversibly impairs long-term memory in mice (Newman et al, 2011; Suzuki et al, 2011).”
A cellular perspective on brain energy metabolism and functional imaging. (2015, background): “The occurrence of this metabolic process is substantiated by the elevated lactate levels detected bymicrosensors and microdialysis in rodents and by MRS in humans in the activated area (Hu and Wilson, 1997; Just et al., 2013; Prichard et al., 1991; Sappey-Marinier et al., 1992; Schaller et al., 2013”
Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. (2011, background): “…that astrocyte-neuron interactions at the energy metabolism level (in particular through lactate release by astrocytes) also influence higher brain functions (Ainscow et al., 2002; Lam et al., 2005; Shimizu et al., 2007; Erlichman et al., 2008; Parsons and Hirasawa, 2010; Suzuki et al., 2011).”