title: Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo.
abstract: Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF). Activity-dependent rises in CMRO(2) fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca(2+) stimulate oxidative metabolism via mitochondrial signaling, but whether this also occurs in the intact brain is unknown. Here we applied a pharmacological approach to dissect the effects of ionic currents and cytosolic Ca(2+) rises of neuronal origin on activity-dependent rises in CMRO(2). We used two-photon microscopy and current source density analysis to study real-time Ca(2+) dynamics and transmembrane ionic currents in relation to CMRO(2) in the mouse cerebellar cortex in vivo. We report a direct correlation between CMRO(2) and summed (i.e., the sum of excitatory, negative currents during the whole stimulation period) field EPSCs (∑fEPSCs) in Purkinje cells (PCs) in response to stimulation of the climbing fiber (CF) pathway. Blocking stimulus-evoked rises in cytosolic Ca(2+) in PCs with the P/Q-type channel blocker ω-agatoxin-IVA (ω-AGA), or the GABA(A) receptor agonist muscimol, did not lead to a time-locked reduction in CMRO(2), and excitatory synaptic or action potential currents. During stimulation, neither ω-AGA or (μ-oxo)-bis-(trans-formatotetramine-ruthenium) (Ru360), a mitochondrial Ca(2+) uniporter inhibitor, affected the ratio of CMRO(2) to fEPSCs or evoked local field potentials. However, baseline CBF and CMRO(2) decreased gradually with Ru360. Our data suggest that in vivo activity-dependent rises in CMRO(2) are correlated with synaptic currents and postsynaptic spiking in PCs. Our study did not reveal a unique role of neuronal cytosolic Ca(2+) signals in controlling CMRO(2) increases during CF stimulation.
authors.affiliation: Department of Neuroscience and Pharmacology, and Center for Healthy Aging, University of Copenhagen, DK-2200 Copenhagen N, Denmark. mathiesenator@gmail.com
authors.forename: Claus
authors.initials: C
authors.lastname: Mathiesen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Caesar
authors.forename: Kirsten
authors.initials: K
authors.lastname: Thomsen
authors.forename: Tycho M
authors.initials: TM
authors.lastname: Hoogland
authors.forename: Brent M
authors.initials: BM
authors.lastname: Witgen
authors.forename: Alexey
authors.initials: A
authors.lastname: Brazhe
authors.forename: Martin
authors.initials: M
authors.lastname: Lauritzen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002531:Cerebellum / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology*; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D020867:omega-Agatoxin IVA / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020867:omega-Agatoxin IVA; D002118:Calcium