Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo: Calcium, synaptic currents and oxygen

Claus Mathiesen; Kirsten Caesar; Kirsten Joan Thomsen; Tycho Hoogland; Brent Marvin Witgen; Alexey Brazhe; Martin Lauritzen

Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo: Calcium, synaptic currents and oxygen

Claus Mathiesen, Kirsten Caesar, Kirsten Joan Thomsen, Tycho Hoogland, Brent Marvin Witgen, Alexey Brazhe, Martin Lauritzen

Abstract

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.

Translated title of the contribution	Aktivitets-afhængig øgning af lokal ilt forbrug korrelerer med post-synaptisk strøm i mus cerebellar kortex: calcium, synaptisk strøm og ilt
Original language	English
Journal	Journal of Neuroscience
Volume	31
Issue number	50
Pages (from-to)	18327-37
Number of pages	10
ISSN	0270-6474
Publication status	Published - 14 Dec 2011

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http://www.ncbi.nlm.nih.gov/pubmed/22171036

Cite this

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 et al.

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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title = "Activity-dependent increases in local oxygen consumption correlate with post-synaptic currents in the mouse cerebellum in vivo: Calcium, synaptic currents and oxygen",

abstract = "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.",

author = "Claus Mathiesen and Kirsten Caesar and Thomsen, {Kirsten Joan} and Tycho Hoogland and Witgen, {Brent Marvin} and Alexey Brazhe and Martin Lauritzen",

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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

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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

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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 -