title: Lactate-mediated glia-neuronal signalling in the mammalian brain.
abstract: Astrocytes produce and release L-lactate as a potential source of energy for neurons. Here we present evidence that L-lactate, independently of its caloric value, serves as an astrocytic signalling molecule in the locus coeruleus (LC). The LC is the principal source of norepinephrine to the frontal brain and thus one of the most influential modulatory centers of the brain. Optogenetically activated astrocytes release L-lactate, which excites LC neurons and triggers release of norepinephrine. Exogenous L-lactate within the physiologically relevant concentration range mimics these effects. L-lactate effects are concentration-dependent, stereo-selective, independent of L-lactate uptake into neurons and involve a cAMP-mediated step. In vivo injections of L-lactate in the LC evokes arousal similar to the excitatory transmitter, L-glutamate. Our results imply the existence of an unknown receptor for this 'glio-transmitter'.
authors: 1] School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK [2].
authors: F
authors: F
authors: Tang
authors: 1] School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK [2].
authors: S
authors: S
authors: Lane
authors: Department of Neuroscience, Physiology & Pharmacology, University College London, London WC1E 6BT, UK.
authors: A
authors: A
authors: Korsak
authors: School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors: J F R
authors: JF
authors: Paton
authors: Department of Neuroscience, Physiology & Pharmacology, University College London, London WC1E 6BT, UK.
authors: A V
authors: AV
authors: Gourine
authors: School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors: S
authors: S
authors: Kasparov
authors: School of Physiology and Pharmacology, University of Bristol, Bristol BS8 1TD, UK.
authors: A G
authors: AG
authors: Teschemacher
mesh_terms: D059331:Adrenergic Neurons / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism*; D008125:Locus Coeruleus / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction
chemical_list: D019344:Lactic Acid; D009638:Norepinephrine