Comprehensive Summary
This study demonstrates that lactate transport and exchange are not necessary for sustained synchronized synaptic transmission in persistent gamma oscillations (~40Hz), and sharp wave-ripples (~250Hz). Using AR-C155858, monocarboxylate transporters 1 and 2 -- glial MCT1 and neuronal MCT2 -- were blocked in rat hippocampal slices that generate gamma oscillations and mouse slices that generate sharp wave-ripples. Lactate concentration was measured in all slices supplied with glucose using Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The tissues demonstrated lactate production within the tissue and blocking the transporters did not disrupt synchronized synaptic transmission when glucose was available. However, when provided with low glucose and lactate was supplied instead, inhibiting the transporters lowered the synchronized frequency oscillations. When provided with low glucose, gamma oscillation decreased by 86%. However, supplying lactate gave partial recovery to an only 46% reduction. The study demonstrated that lactate transport is important in low glucose environments, but is not necessary for synchronized synaptic transmission in the presence of glucose.
Outcomes and Implications
Understanding lactate shuttling its impact on sustained synchronized synaptic transmission is important to understanding the neural network oscillations that are responsible for higher brain functions. This study contributes to better understanding of potential clinical diseases and diagnosis where the brain is under metabolic stress. Such as disruptions in MCT1 or MCT2 functioning potentially worsening outcomes in metabolic or neurodegenerative diseases that impair energy metabolism.