GLUCOSE AND LACTATE PLAY DISTINCT ROLES IN SUSTAINING NEURONAL FUNCTIONS

The brain represents 2% of body weight but consumes 20% of the body’s glucose: 80% is used by neurons and 20% by astrocytes and other glial cells. While neurons were long thought to rely exclusively on glucose via GLUT3-dependent uptake, growing evidence highlights a role for astrocyte-derived lactate as an energy source, thereby leaving neuronal glucose available for functions such as coping with oxidative stress. Astrocytes, positioned between blood vessels and synapses, take up glucose and convert it into lactate. Lactate is released via MCT1/MCT4 transporters and taken up by neurons through MCT2 to generate ATP. Understanding when and how neurons switch between glucose and lactate as energy sources, and what the non-metabolic functions of glucose are, remain fundamental questions in the field of brain energetics. Our aim was to determine whether the choice of energy source depends on energy demand. We used a viral approach to downregulate either the neuronal glucose transporter GLUT3, the neuronal lactate transporter MCT2, or the astrocytic lactate transporters MCT1/MCT4 in the rat somatosensory cortex. During whole-cell patch-clamp recordings, basal synaptic transmission was assessed via miniature excitatory postsynaptic events, and neuronal excitability by firing frequency. Our data indicate that glucose and lactate regulate basal synaptic transmission. Regarding excitability, our data indicate that glucose plays a gatekeeper role. These findings reveal distinct roles for glucose and lactate in regulating neuronal functions.