title: Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo.
abstract: Neuronal activity is tightly coupled with brain energy metabolism. Numerous studies have suggested that lactate is equally important as an energy substrate for neurons as glucose. Lactate production is reportedly triggered by glutamate uptake, and independent of glutamate receptor activation. Here we show that climbing fibre stimulation of cerebellar Purkinje cells increased extracellular lactate by 30% within 30 s of stimulation, but not for briefer stimulation periods. To explore whether lactate production was controlled by pre- or postsynaptic events we silenced AMPA receptors with CNQX. This blocked all evoked rises in postsynaptic activity, blood flow, and glucose and oxygen consumption. CNQX also abolished rises in lactate concomitantly with marked reduction in postsynaptic currents. Rises in lactate were unaffected by inhibition of glycogen phosphorylase, suggesting that lactate production was independent of glycogen breakdown. Stimulated lactate production in cerebellum is derived directly from glucose uptake, and coupled to neuronal activity via AMPA receptor activation.
authors.affiliation: Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Caesar
authors.forename: Parastoo
authors.initials: P
authors.lastname: Hashemi
authors.forename: Aicha
authors.initials: A
authors.lastname: Douhou
authors.forename: Gilles
authors.initials: G
authors.lastname: Bonvento
authors.forename: Martyn G
authors.initials: MG
authors.lastname: Boutelle
authors.forename: Anne B
authors.initials: AB
authors.lastname: Walls
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D002531:Cerebellum / Q000098:blood supply / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D009457:Neuroglia / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism*; D011689:Purkinje Cells / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D012039:Regional Blood Flow / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology
chemical_list: D018691:Excitatory Amino Acid Antagonists; D007773:Lactates; D018091:Receptors, AMPA; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D005947:Glucose; D010100:Oxygen