A TEMPORARY LOCAL ENERGY POOL COUPLED TO NEURONAL-ACTIVITY - FLUCTUATIONS OF EXTRACELLULAR LACTATE LEVELS IN RAT-BRAIN MONITORED WITH RAPID-RESPONSE ENZYME-BASED SENSOR

A successfully developed enzyme-based lactate microsensor with rapid r esponse time allows the direct and continuous in vivo measurement of l actic acid concentration with high temporal resolution in brain extrac ellular fluid. The fluctuations coupled to neuronal activity in extrac ellular lactate concentration were explored in the dentate gyrus of th e hippocampus of the rat brain after electrical stimulation of the per forant pathway. Extracellular glucose and oxygen levels were also dete cted simultaneously by coimplantation of a fast-response glucose senso r and an oxygen electrode, to provide novel information of trafficking of energy substances in real time related to local neuronal activity. The results first give a comprehensive picture of complementary energ y supply and use of lactate and glucose in the intact brain tissue. In response to acute neuronal activation, the brain tissue shifts immedi ately to significant energy supply by lactate. A local temporary fuel ''reservoir'' is established behind the blood-brain barrier, evidenced by increased extracellular lactate concentration. The pool can be dep leted rapidly, up to 28% in 10-12 s, by massive, acute neuronal use af ter stimulation and can be replenished in similar to 20 s. Glutamate-s timulated astrocytic glycolysis and the increase of regional blood flo w may regulate the lactate concentration of the pool in different time scales to maintain local energy homeostasis.