Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

TY - JOUR

T1 - Activity-dependent increases in local oxygen consumption correlate with postsynaptic currents in the mouse cerebellum in vivo

AU - Mathiesen, Claus

AU - Caesar, Kirsten

AU - Thomsen, Kirsten Engelund

AU - Hoogland, Tycho M

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 (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-(transformatotetramine-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.

AB - 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-(transformatotetramine-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.

U2 - http://dx.doi.org/10.1523/JNEUROSCI.4526-11.2011

DO - http://dx.doi.org/10.1523/JNEUROSCI.4526-11.2011

M3 - Journal article

SN - 0270-6474

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

IS - 50

ER -