Lactate as a supplemental fuel for synaptic transmission and neuronal network oscillations: Potentials and limitations.
Level 5 - mechanism / opinion, no new human data
Narrative review of ex vivo preclinical and bench electrophysiology studies
PubMed 37309602 · doi:10.1111/jnc.15867
What was done
This review synthesized findings from electrophysiological studies in ex vivo hippocampal slice preparations (using electrical stimulation, optogenetic tools, and receptor ligands) evaluating whether lactate can substitute for glucose to sustain synaptic transmission and various neural network activation states.
What was found
The reviewed literature indicates that lactate without glucose impairs high-energy demand states (cerebral metabolic rate of oxygen, CMRO2, set to 100%), including gamma (30-70 Hz) and theta-gamma oscillations, causing oscillation attenuation or moderate neural bursting. Bursting is suppressed by elevating the glucose fraction. Conversely, lactate sustains lower-energy activity such as sharp wave-ripples (CMRO2 ~65%), where lactate increases oxygen consumption by about 9%. Additionally, lactate attenuates neurotransmission in glutamatergic pyramidal cells and fast-spiking GABAergic interneurons by reducing presynaptic neurotransmitter release, while axonal action potential generation and propagation remain regular.
Why it matters
The paper clarifies the metabolic constraints of lactate oxidation in the brain, showing that lactate cannot fully replace glucose during high-energy network rhythms that require aerobic glycolysis.
Limits
The conclusions are drawn from narrative synthesis of ex vivo brain slice preparations, which lack intact systemic metabolism and vascular regulation. No systematic review methodology, study count (n), or human clinical data are reported.
Cited by
- supports The brain can use lactate as an energy fuel, albeit to lower levels than glucose and ketones.