Activity-dependent Increases in Local Oxygen Consumption Correlate with Postsynaptic Currents in the Mouse Cerebellum In Vivo

被引:33
作者
Mathiesen, Claus [1 ,2 ]
Caesar, Kirsten [2 ]
Thomsen, Kirsten [2 ]
Hoogland, Tycho M. [3 ]
Witgen, Brent M. [2 ]
Brazhe, Alexey [4 ]
Lauritzen, Martin [2 ,5 ]
机构
[1] Univ Copenhagen, Inst Neurosci & Pharmacol, Panum Inst 18 5, Dept Neurosci & Pharmacol, DK-2200 Copenhagen N, Denmark
[2] Univ Copenhagen, Ctr Hlth Aging, DK-2200 Copenhagen N, Denmark
[3] Netherlands Inst Neurosci, NL-1000 GC Amsterdam, Netherlands
[4] Moscow MV Lomonosov State Univ, Fac Biol, Moscow 119991, Russia
[5] Glostrup Cty Hosp, Dept Clin Neurophysiol, DK-2600 Glostrup, Denmark
基金
英国医学研究理事会;
关键词
CEREBRAL-BLOOD-FLOW; RAT-BRAIN; SYNAPTIC ACTIVITY; CALCIUM; CORTEX; CA2+; MITOCHONDRIA; CHANNELS; INHIBITION; INCREMENTS;
D O I
10.1523/JNEUROSCI.4526-11.2011
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Evoked neural activity correlates strongly with rises in cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF). 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 (i.e., the sum of excitatory, negative currents during the whole stimulation period) field EPSCs (Sigma fEPSCs) in Purkinje cells (PCs) in response to stimulation of the climbing fiber (CF) pathway. Blocking stimulus-evoked rises in cytosolic Ca2+ in PCs with the P/Q-type channel blocker omega-agatoxin-IVA (omega-AGA), or the GABA(A) receptor agonist muscimol, did not lead to a time-locked reduction in CMRO2, and excitatory synaptic or action potential currents. During stimulation, neither omega-AGA or (mu-oxo)-bis-(transformatotetramine-ruthenium) (Ru360), a mitochondrial Ca2+ uniporter inhibitor, affected the ratio of CMRO2 to fEPSCs or evoked local field potentials. 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.
引用
收藏
页码:18327 / 18337
页数:11
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