Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo: Calcium, synaptic currents and oxygen
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Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo : Calcium, synaptic currents and oxygen. / Mathiesen, Claus; Caesar, Kirsten; Thomsen, Kirsten Joan; Hoogland, Tycho; Witgen, Brent Marvin; Brazhe, Alexey; Lauritzen, Martin.
In: Journal of Neuroscience, Vol. 31, No. 50, 14.12.2011, p. 18327-37.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo
T2 - Calcium, synaptic currents and oxygen
AU - Mathiesen, Claus
AU - Caesar, Kirsten
AU - Thomsen, Kirsten Joan
AU - Hoogland, Tycho
AU - Witgen, Brent Marvin
AU - Brazhe, Alexey
AU - Lauritzen, Martin
PY - 2011/12/14
Y1 - 2011/12/14
N2 - Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow. Activity-dependent rises in CMRO2 fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca2+ 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 Ca2+ rises of neuronal origin on activity-dependent rises in CMRO2. We used two-photon microscopy and current source density analysis to study real-time Ca2+ dynamics and transmembrane ionic currents in relation to CMRO2 in the mouse cerebellar cortex in vivo. We report a direct correlation between CMRO2 and summed field excitatory postsynaptic currents (SfEPSC) in Purkinje cells (PCs) in response to stimulation of the climbing fiber pathway (CF). Blocking stimulus-evoked rises in cytosolic Ca2+ in PCs with the P/Q-type channel blocker ¿-agatoxin-IVA (¿-AGA), or the GABAA receptor agonist muscimol, did not lead to a time-locked reduction in CMRO2, excitatory synaptic or action potential currents. During stimulation, neither ¿-AGA or (µ-oxo)-bis-(trans-formatotetramine-ruthenium) (Ru360), a mitochondrial Ca2+ uniporter inhibitor, affected the ratio of CMRO2 to fEPSCs or evoked local field potentials (LFPs). However, baseline CBF and CMRO2 decreased gradually with Ru360. Our data suggest that in vivo activity-dependent rises in CMRO2 are correlated with synaptic currents and postsynaptic spiking in PCs. Our study did not reveal a unique role of neuronal cytosolic Ca2+ signals in controlling CMRO2 increases during CF stimulation.
AB - Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow. Activity-dependent rises in CMRO2 fluctuate with ATP turnover due to ion pumping. In vitro studies suggest that increases in cytosolic Ca2+ 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 Ca2+ rises of neuronal origin on activity-dependent rises in CMRO2. We used two-photon microscopy and current source density analysis to study real-time Ca2+ dynamics and transmembrane ionic currents in relation to CMRO2 in the mouse cerebellar cortex in vivo. We report a direct correlation between CMRO2 and summed field excitatory postsynaptic currents (SfEPSC) in Purkinje cells (PCs) in response to stimulation of the climbing fiber pathway (CF). Blocking stimulus-evoked rises in cytosolic Ca2+ in PCs with the P/Q-type channel blocker ¿-agatoxin-IVA (¿-AGA), or the GABAA receptor agonist muscimol, did not lead to a time-locked reduction in CMRO2, excitatory synaptic or action potential currents. During stimulation, neither ¿-AGA or (µ-oxo)-bis-(trans-formatotetramine-ruthenium) (Ru360), a mitochondrial Ca2+ uniporter inhibitor, affected the ratio of CMRO2 to fEPSCs or evoked local field potentials (LFPs). However, baseline CBF and CMRO2 decreased gradually with Ru360. Our data suggest that in vivo activity-dependent rises in CMRO2 are correlated with synaptic currents and postsynaptic spiking in PCs. Our study did not reveal a unique role of neuronal cytosolic Ca2+ signals in controlling CMRO2 increases during CF stimulation.
M3 - Journal article
VL - 31
SP - 18327
EP - 18337
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
SN - 0270-6474
IS - 50
ER -
ID: 38462169