HCAR1-mediated lactate signaling: implications for neuronal excitability and nervous system function

The limited understanding of the role of lactate in the nervous system we had in the past conferred to this metabolite negative connotation since it was mostly considered a hallmark of oxygen deprivation. This view has been drastically changed by scientific advances that highlighted the fundamental role of lactate in neuroprotection, cognition and as neuronal fuel. The discovery that lactate is the specific ligand of the GPCR receptor HCAR1 also brought to light the ability of lactate to initiate several intracellular pathways regulating important processes like neurodevelopment, neurogenesis, angiogenesis and motor learning. Lactate signaling via HCAR1 serves as neuromodulatory pathway regulating neuronal firing by means of heterogenous cascades exhibiting region specificity. This Mini Review focuses on the progresses made in understanding these processes and their implications for neuronal modulation both in physiological and pathological conditions.