Abstract
Tight coupling of neuronal metabolism to synaptic activity is critical to ensure that the supply of metabolic substrates meets the demands of neuronal signaling. Given the impact of temperature on metabolism, and the wide fluctuations of brain temperature observed during clinical hypothermia, we examined the effect of temperature on neurometabolic coupling. Intrinsic fluorescence signals of the oxidized form of flavin adenine dinucleotide (FAD) and the reduced form of nicotinamide adenine dinucleotide (NADH), and their ratios, were measured to assess neural metabolic state and local field potentials were recorded to measure synaptic activity in the mouse brain. Brain slice preparations were used to remove the potential impacts of blood flow. Tight coupling between metabolic signals and local field potential amplitudes was observed at a range of temperatures below 29 °C. However, above 29 °C, the metabolic and synaptic signatures diverged such that FAD signals were diminished, but local field potentials retained their amplitude. It was also observed that the declines in the FAD signals seen at high temperatures (and hence the decoupling between synaptic and metabolic events) are driven by low FAD availability at high temperatures. These data suggest that neurometabolic coupling, thought to be critical for ensuring the metabolic health of the brain, may show temperature dependence, and is related to temperature-dependent changes in FAD supplies.
Similar content being viewed by others
References
Aihara H, Okada Y, Tamaki N (2001) The effects of cooling and rewarming on the neuronal activity of pyramidal neurons in guinea pig hippocampal slices. Brain Res 893:36–45
Al-Juboori SI, Dondzillo A, Stubblefield EA, Felsen G, Lei TC, Klug A (2013) Light scattering properties vary across different regions of the adult mouse brain. PLoS One 8:e67626. doi:10.1371/journal.pone.0067626
Alva N, Palomeque J, Carbonell T (2013) Oxidative stress and antioxidant activity in hypothermia and rewarming: can RONS modulate the beneficial effects of therapeutic hypothermia? Oxidative Med Cell Longev 2013:957054. doi:10.1155/2013/957054
Belanger M, Allaman I, Magistretti PJ (2011) Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation. Cell Metab 14:724–738. doi:10.1016/j.cmet.2011.08.016
Bernard SA, Gray TW, Buist MD, Jones BM, Silvester W, Gutteridge G, Smith K (2002) Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. N Engl J Med 346:557–563. doi:10.1056/NEJMoa003289
Burlington RF, Wiebers JE (1967) The effect of temperature on glycolysis in brain and skeletal muscle from a hibernator and a non-hibernator. Physiol Zool 40:201–206
Bingmann D, Kolde G (1982) PO2-profiles in hippocampal slices of the guinea pig. Exp Brain Res 48:89–96
Buzatu S (2009) The temperature-induced changes in membrane potential. Riv Biol 102:199–217
Chih CP, Lipton P, Roberts EL Jr (2001) Do active cerebral neurons really use lactate rather than glucose? Trends Neurosci 24:573–578
Christoforides C, Hedley-Whyte J (1969) Effect of temperature and hemoglobin concentration on solubility of O2 in blood. J Appl Physiol 27:592–596
Cooper JM, Gadian DG, Jentschke S, Goldman A, Munoz M, Pitts G, Banks T, Chong WK, Hoskote A, Deanfield J, Baldeweg T, de Haan M, Mishkin M, Vargha-Khadem F (2015) Neonatal hypoxia, hippocampal atrophy, and memory impairment: evidence of a causal sequence. Cereb Cortex 25:1469–1476. doi:10.1093/cercor/bht332
Costa C, Belcastro V, Tozzi A, Di Filippo M, Tantucci M, Siliquini S, Autuori A, Picconi B, Spillantini MG, Fedele E, Pittaluga A, Raiteri M, Calabresi P (2008) Electrophysiology and pharmacology of striatal neuronal dysfunction induced by mitochondrial complex I inhibition. J Neurosci 28:8040–8052. doi:10.1523/JNEUROSCI.1947-08.2008
Coutinho V, Mutoh H, Knopfel T (2004) Functional topology of the mossy fibre-granule cell—Purkinje cell system revealed by imaging of intrinsic fluorescence in mouse cerebellum. Eur J Neurosci 20:740–748. doi:10.1111/j.1460-9568.2004.03533.x
Cruikshank SJ, Rose HJ, Metherate R (2002) Auditory thalamocortical synaptic transmission in vitro. J Neurophysiol 87:361–384
de la Pena E, Malkia A, Vara H, Caires R, Ballesta JJ, Belmonte C, Viana F (2012) The influence of cold temperature on cellular excitability of hippocampal networks. PLoS One 7:e52475. doi:10.1371/journal.pone.0052475
Dong B (1997) Progresses in the study of ultrasonics in China, 1997. Zhonghua Yi Xue Za Zhi 77:927–929
Dufour S, Rousse N, Canioni P, Diolez P (1996) Top-down control analysis of temperature effect on oxidative phosphorylation. Biochem J 314(Pt 3):743–751
Edelstein A, Amodaj N, Hoover K, Vale R, Stuurman N (2010) Computer control of microscopes using microManager. Curr Protoc Mol Biol Chapter 14:Unit14 20. doi:10.1002/0471142727.mb1420s92
Erecinska M, Thoresen M, Silver IA (2003) Effects of hypothermia on energy metabolism in mammalian central nervous system. J Cereb Blood Flow Metab 23:513–530. doi:10.1097/01.WCB.0000066287.21705.21
Foster KA, Beaver CJ, Turner DA (2005) Interaction between tissue oxygen tension and NADH imaging during synaptic stimulation and hypoxia in rat hippocampal slices. Neuroscience 132:645–657. doi:10.1016/j.neuroscience.2005.01.040
Galeffi F, Somjen GG, Foster KA, Turner DA (2011) Simultaneous monitoring of tissue PO2 and NADH fluorescence during synaptic stimulation and spreading depression reveals a transient dissociation between oxygen utilization and mitochondrial redox state in rat hippocampal slices. J Cereb Blood Flow Metab 31:626–639. doi:10.1038/jcbfm.2010.136
Gao W, Chen G, Reinert KC, Ebner TJ (2006) Cerebellar cortical molecular layer inhibition is organized in parasagittal zones. J Neurosci 26:8377–8387. doi:10.1523/JNEUROSCI.2434-06.2006
Garofalo O, Cox DW, Bachelard HS (1988) Brain levels of NADH and NAD+ under hypoxic and hypoglycaemic conditions in vitro. J Neurochem 51:172–176
Gerich FJ, Funke F, Hildebrandt B, Fasshauer M, Muller M (2009) H(2)O(2)-mediated modulation of cytosolic signaling and organelle function in rat hippocampus. Pflugers Arch 458:937–952. doi:10.1007/s00424-009-0672-0
Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A, Gunn AJ (2005) Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 365:663–670. doi:10.1016/S0140-6736(05)17946-X
Gosseries O, Demertzi A, Noirhomme Q, Tshibanda J, Boly M, Op de Beeck M, Hustinx R, Maquet P, Salmon E, Moonen G, Luxen A, Laureys S, De Tiege X (2008) Functional neuroimaging (fMRI, PET and MEG): what do we measure? Rev Med Liege 63:231–237
Grosser E, Hirt U, Janc OA, Menzfeld C, Fischer M, Kempkes B, Vogelgesang S, Manzke TU, Opitz L, Salinas-Riester G, Muller M (2012) Oxidative burden and mitochondrial dysfunction in a mouse model of Rett syndrome. Neurobiol Dis 48:102–114. doi:10.1016/j.nbd.2012.06.007
Hagerdal M, Harp J, Siesjo BK (1975) Effect of hypothermia upon organic phosphates, glycolytic metabolites, citric acid cycle intermediates and associated amino acids in rat cerebral cortex. J Neurochem 24:743–748
Hajos N, Mody I (2009) Establishing a physiological environment for visualized in vitro brain slice recordings by increasing oxygen supply and modifying aCSF content. J Neurosci Methods 183:107–113. doi:10.1016/j.jneumeth.2009.06.005
Hajos N, Ellender TJ, Zemankovics R, Mann EO, Exley R, Cragg SJ, Freund TF, Paulsen O (2009) Maintaining network activity in submerged hippocampal slices: importance of oxygen supply. Eur J Neurosci 29:319–327. doi:10.1111/j.1460-9568.2008.06577.x
Hillered L, Chan PH (1988) Effects of arachidonic acid on respiratory activities in isolated brain mitochondria. J Neurosci Res 19:94–100. doi:10.1002/jnr.490190113
Hishida R, Kudoh M, Shibuki K (2014) Multimodal cortical sensory pathways revealed by sequential transcranial electrical stimulation in mice. Neurosci Res 87:49–55. doi:10.1016/j.neures.2014.07.004
Hodgman C (1958-1959) Handbook of chemistry and physics—fortieth edition. Chemical Rubber Publishing, Co., Cleveland
Horie M, Tsukano H, Takebayashi H, Shibuki K (2015) Specific distribution of non-phosphorylated neurofilaments characterizing each subfield in the mouse auditory cortex. Neurosci Lett 606:182–187. doi:10.1016/j.neulet.2015.08.055
Huchzermeyer C, Albus K, Gabriel HJ, Otahal J, Taubenberger N, Heinemann U, Kovacs R, Kann O (2008) Gamma oscillations and spontaneous network activity in the hippocampus are highly sensitive to decreases in pO2 and concomitant changes in mitochondrial redox state. J Neurosci 28:1153–1162. doi:10.1523/JNEUROSCI.4105-07.2008
Husson TR, Issa NP (2009) Functional imaging with mitochondrial flavoprotein autofluorescence theory, practice, and applications. Front Neurosci 221–253. doi:10.1201/9781420076851
Hypothermia after Cardiac Arrest Study G (2002) Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. N Engl J Med 346:549–556. doi:10.1056/NEJMoa012689
Ivanov A, Zilberter Y (2011) Critical state of energy metabolism in brain slices: the principal role of oxygen delivery and energy substrates in shaping neuronal activity. Front Neuroenerg 3:9. doi:10.3389/fnene.2011.00009
Ivanov AI, Malkov AE, Waseem T, Mukhtarov M, Buldakova S, Gubkina O, Zilberter M, Zilberter Y (2014) Glycolysis and oxidative phosphorylation in neurons and astrocytes during network activity in hippocampal slices. J Cereb Blood Flow Metab 34:397–407. doi:10.1038/jcbfm.2013.222
Ivanov AI, Bernard C, Turner DA (2015) Metabolic responses differentiate between interictal, ictal and persistent epileptiform activity in intact, immature hippocampus in vitro. Neurobiol Dis 75:1–14. doi:10.1016/j.nbd.2014.12.013
Jarmuszkiewicz W, Woyda-Ploszczyca A, Koziel A, Majerczak J, Zoladz JA (2015) Temperature controls oxidative phosphorylation and reactive oxygen species production through uncoupling in rat skeletal muscle mitochondria. Free Radic Biol Med 83:12–20. doi:10.1016/j.freeradbiomed.2015.02.012
Ji S, Chance B, Stuart BH, Nathan R (1977) Two-dimensional analysis of the redox state of the rat cerebral cortex in vivo by NADH fluorescence photography. Brain Res 119:357–373
Johnston D, Brown TH (1981) Giant synaptic potential hypothesis for epileptiform activity. Science 211:294–297
Jotty K, Shuttleworth CW, Valenzuela CF (2015) Characterization of activity-dependent changes in flavoprotein fluorescence in cerebellar slices from juvenile rats. Neurosci Lett 584:17–22. doi:10.1016/j.neulet.2014.09.052
Kaibara T, Sutherland GR, Colbourne F, Tyson RL (1999) Hypothermia: depression of tricarboxylic acid cycle flux and evidence for pentose phosphate shunt upregulation. J Neurosurg 90:339–347. doi:10.3171/jns.1999.90.2.0339
Kann O, Kovacs R, Njunting M, Behrens CJ, Otahal J, Lehmann TN, Gabriel S, Heinemann U (2005) Metabolic dysfunction during neuronal activation in the ex vivo hippocampus from chronic epileptic rats and humans. Brain 128:2396–2407. doi:10.1093/brain/awh568
Kann O, Huchzermeyer C, Kovacs R, Wirtz S, Schuelke M (2011) Gamma oscillations in the hippocampus require high complex I gene expression and strong functional performance of mitochondria. Brain 134:345–358. doi:10.1093/brain/awq333
Kasischke KA, Vishwasrao HD, Fisher PJ, Zipfel WR, Webb WW (2004) Neural activity triggers neuronal oxidative metabolism followed by astrocytic glycolysis. Science 305:99–103. doi:10.1126/science.1096485
Kim JA, Connors BW (2012) High temperatures alter physiological properties of pyramidal cells and inhibitory interneurons in hippocampus. Front Cell Neurosci 6:27. doi:10.3389/fncel.2012.00027
Kim DY, Vallejo J, Rho JM (2010) Ketones prevent synaptic dysfunction induced by mitochondrial respiratory complex inhibitors. J Neurochem 114:130–141. doi:10.1111/j.1471-4159.2010.06728.x
Kimura R, Ma LY, Wu C, Turner D, Shen JX, Ellsworth K, Wakui M, Maalouf M, Wu J (2012) Acute exposure to the mitochondrial complex I toxin rotenone impairs synaptic long-term potentiation in rat hippocampal slices. CNS Neurosci Ther 18:641–646. doi:10.1111/j.1755-5949.2012.00337.x
Koehn J, Kollmar R, Cimpianu CL, Kallmunzer B, Moeller S, Schwab S, Hilz MJ (2012) Head and neck cooling decreases tympanic and skin temperature, but significantly increases blood pressure. Stroke 43:2142–2148. doi:10.1161/STROKEAHA.112.652248
Kowalska A, Gyugos M, Szego D, Pineda AL, Ayala D, Xu Y, Hughes N, Tito A, Jabłonska J (2007) The thermal scanning fluorescence study on the conformational stability of glucose oxidase (GOD) from Aspergillus niger. Food Chem Biotechnol 71:35–48
Kubota Y, Kamatani D, Tsukano H, Ohshima S, Takahashi K, Hishida R, Kudoh M, Takahashi S, Shibuki K (2008) Transcranial photo-inactivation of neural activities in the mouse auditory cortex. Neurosci Res 60:422–430. doi:10.1016/j.neures.2007.12.013
Lee JC, Callaway JC, Foehring RC (2005) Effects of temperature on calcium transients and Ca2+-dependent afterhyperpolarizations in neocortical pyramidal neurons. J Neurophysiol 93:2012–2020. doi:10.1152/jn.01017.2004
Li LZ, Xu HN, Ranji M, Nioka S, Chance B (2009) Mitochondrial redox imaging for cancer diagnostic and therapeutic studies. J Innov Opt Health Sci 2:325–341. doi:10.1142/S1793545809000735
Llano DA, Theyel BB, Mallik AK, Sherman SM, Issa NP (2009) Rapid and sensitive mapping of long-range connections in vitro using flavoprotein autofluorescence imaging combined with laser photostimulation. J Neurophysiol 101:3325–3340. doi:10.1152/jn.91291.2008
Llano DA, Turner J, Caspary DM (2012) Diminished cortical inhibition in an aging mouse model of chronic tinnitus. J Neurosci 32:16141–16148. doi:10.1523/JNEUROSCI.2499-12.2012
Llano DA, Slater BJ, Lesicko AM, Stebbings KA (2014) An auditory colliculothalamocortical brain slice preparation in mouse. J Neurophysiol 111:197–207. doi:10.1152/jn.00605.2013
Ma H, Cai Q, Lu W, Sheng ZH, Mochida S (2009) KIF5B motor adaptor syntabulin maintains synaptic transmission in sympathetic neurons. J Neurosci 29:13019–13029. doi:10.1523/JNEUROSCI.2517-09.2009
Magistretti PJ (2006) Neuron-glia metabolic coupling and plasticity. J Exp Biol 209:2304–2311. doi:10.1242/jeb.02208
Magistretti PJ, Allaman I (2015) A cellular perspective on brain energy metabolism and functional imaging. Neuron 86:883–901. doi:10.1016/j.neuron.2015.03.035
Malthankar-Phatak GH, Patel AB, Xia Y, Hong S, Chowdhury GM, Behar KL, Orina IA, Lai JC (2008) Effects of continuous hypoxia on energy metabolism in cultured cerebro-cortical neurons. Brain Res 1229:147–154. doi:10.1016/j.brainres.2008.06.074
Mandeville ET, Ayata C, Zheng Y, Mandeville JB (2017) Translational MR neuroimaging of stroke and recovery. Transl Stroke Res 8:22–32. doi:10.1007/s12975-016-0497-z
Mayevsky A (1984) Brain NADH redox state monitored in vivo by fiber optic surface fluorometry. Brain Res 319:49–68
Mayevsky A, Chance B (1974) Repetitive patterns of metabolic changes during cortical spreading depression of the awake rat. Brain Res 65:529–533
Mayevsky A, Chance B (1982) Intracellular oxidation-reduction state measured in situ by a multichannel fiber-optic surface fluorometer. Science 217:537–540
Mayevsky A, Zarchin N, Friedli CM (1982) Factors affecting the oxygen balance in the awake cerebral cortex exposed to spreading depression. Brain Res 236:93–105
Michiels C (2004) Physiological and pathological responses to hypoxia. Am J Pathol 164:1875–1882. doi:10.1016/S0002-9440(10)63747-9
Middleton JW, Kiritani T, Pedersen C, Turner JG, Shepherd GM, Tzounopoulos T (2011) Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. Proc Natl Acad Sci U S A 108:7601–7606. doi:10.1073/pnas.1100223108
Mori K, Maeda M, Miyazaki M, Iwase H (1998) Effects of mild (33 degrees C) and moderate (29 degrees C) hypothermia on cerebral blood flow and metabolism, lactate, and extracellular glutamate in experimental head injury. Neurol Res 20:719–726
Mrozek S, Vardon F, Geeraerts T (2012) Brain temperature: physiology and pathophysiology after brain injury. Anesthesiol Res Pract 2012:989487. doi:10.1155/2012/989487
Nielsen N, Wetterslev J, Cronberg T, Erlinge D, Gasche Y, Hassager C, Horn J, Hovdenes J, Kjaergaard J, Kuiper M, Pellis T, Stammet P, Wanscher M, Wise MP, Aneman A, Al-Subaie N, Boesgaard S, Bro-Jeppesen J, Brunetti I, Bugge JF, Hingston CD, Juffermans NP, Koopmans M, Kober L, Langorgen J, Lilja G, Moller JE, Rundgren M, Rylander C, Smid O, Werer C, Winkel P, Friberg H, Investigators TTMT (2013) Targeted temperature management at 33 degrees C versus 36 degrees C after cardiac arrest. N Engl J Med 369:2197–2206. doi:10.1056/NEJMoa1310519
Osborne NN, Tobin AB, Ghazi H (1988) Role of inositol trisphosphate as a second messenger in signal transduction processes: an essay. Neurochem Res 13:177–191
Palladino WG, Proctor HJ, Jobsis FF (1983) Effect of hypothermia during hypoxic hypotension on cerebral metabolism. J Surg Res 34:388–393
Pellerin L, Magistretti PJ (1994) Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc Natl Acad Sci U S A 91:10625–10629
Phillips AA, Chan FH, Zheng MM, Krassioukov AV, Ainslie PN (2016) Neurovascular coupling in humans: physiology, methodological advances and clinical implications. J Cereb Blood Flow Metab 36:647–664. doi:10.1177/0271678X15617954
Quinn PJ (1988) Effects of temperature on cell membranes. Symp Soc Exp Biol 42:237–258
Ranji M, Kanemoto S, Matsubara M, Grosso MA, Gorman JH 3rd, Gorman RC, Jaggard DL, Chance B (2006) Fluorescence spectroscopy and imaging of myocardial apoptosis. J Biomed Opt 11:064036. doi:10.1117/1.2400701
Reinert KC, Dunbar RL, Gao W, Chen G, Ebner TJ (2004) Flavoprotein autofluorescence imaging of neuronal activation in the cerebellar cortex in vivo. J Neurophysiol 92:199–211. doi:10.1152/jn.01275.2003
Reinert KC, Gao W, Chen G, Ebner TJ (2007) Flavoprotein autofluorescence imaging in the cerebellar cortex in vivo. J Neurosci Res 85:3221–3232. doi:10.1002/jnr.21348
Reinert KC, Gao W, Chen G, Wang X, Peng YP, Ebner TJ (2011) Cellular and metabolic origins of flavoprotein autofluorescence in the cerebellar cortex in vivo. Cerebellum 10:585–599. doi:10.1007/s12311-011-0278-x
Ricker JH, Hillary FG, DeLuca J (2001) Functionally activated brain imaging (O-15 PET and fMRI) in the study of learning and memory after traumatic brain injury. J Head Trauma Rehabil 16:191–205
Roy CS, Sherrington CS (1890) On the regulation of the blood-supply of the brain. J Physiol 11(85–158):117
Sacktor B, Sanborn R (1956) The effect of temperature on oxidative phosphorylation with insect flight muscle mitochondria. J Biophys Biochem Cytol 2:105–107
Schneider J, Lewen A, Ta TT, Galow LV, Isola R, Papageorgiou IE, Kann O (2015) A reliable model for gamma oscillations in hippocampal tissue. J Neurosci Res 93:1067–1078. doi:10.1002/jnr.23590
Schuh RA, Matthews CC, Fishman PS (2008) Interaction of mitochondrial respiratory inhibitors and excitotoxins potentiates cell death in hippocampal slice cultures. J Neurosci Res 86:3306–3313. doi:10.1002/jnr.21772
Schurr A, Rigor BM (1998) Brain anaerobic lactate production: a suicide note or a survival kit? Dev Neurosci 20:348–357
Sepehr R, Staniszewski K, Maleki S, Jacobs ER, Audi S, Ranji M (2012) Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress. J Biomed Opt 17:046010. doi:10.1117/1.JBO.17.4.046010
Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, SA MD, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD, Finer NN, Carlo WA, Duara S, Oh W, Cotten CM, Stevenson DK, Stoll BJ, Lemons JA, Guillet R, Jobe AH, National Institute of Child H, Human Development Neonatal Research N (2005) Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 353:1574–1584. doi:10.1056/NEJMcps050929
Shibuki K, Hishida R, Murakami H, Kudoh M, Kawaguchi T, Watanabe M, Watanabe S, Kouuchi T, Tanaka R (2003) Dynamic imaging of somatosensory cortical activity in the rat visualized by flavoprotein autofluorescence. J Physiol 549:919–927. doi:10.1113/jphysiol.2003.040709
Shuttleworth CW (2010) Use of NAD(P)H and flavoprotein autofluorescence transients to probe neuron and astrocyte responses to synaptic activation. Neurochem Int 56:379–386. doi:10.1016/j.neuint.2009.12.015
Shuttleworth CW, Brennan AM, Connor JA (2003) NAD(P)H fluorescence imaging of postsynaptic neuronal activation in murine hippocampal slices. J Neurosci 23:3196–3208
Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG (1998) Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci U S A 95:316–321
Slater BJ, Fan AY, Stebbings KA, Saif MT, Llano DA (2015) Modification of a colliculo-thalamocortical mouse brain slice, incorporating 3-D printing of chamber components and multi-scale optical imaging. J Vis Exp doi:10.3791/53067
Stebbings KA, Choi HW, Ravindra A, Caspary DM, Turner JG, Llano DA (2016) Ageing-related changes in GABAergic inhibition in mouse auditory cortex, measured using in vitro flavoprotein autofluorescence imaging. J Physiol 594:207–221. doi:10.1113/JP271221
Steriade M, Amzica F (1999) Intracellular study of excitability in the seizure-prone neocortex in vivo. J Neurophysiol 82:3108–3122
Vanzetta I, Flynn C, Ivanov AI, Bernard C, Benar CG (2010) Investigation of linear coupling between single-event blood flow responses and interictal discharges in a model of experimental epilepsy. J Neurophysiol 103:3139–3152. doi:10.1152/jn.01048.2009
Varela C, Llano DA, Theyel BB (2012) An introduction to in vitro slice approaches for the study of neuronal circuitry. NeuroMethods 67:103–125. doi:10.1007/7657_2011_19
Vazquez AL, Masamoto K, Fukuda M, Kim SG (2010) Cerebral oxygen delivery and consumption during evoked neural activity. Front Neuroenerg 2:11. doi:10.3389/fnene.2010.00011
Vazquez AL, Fukuda M, Kim SG (2012) Evolution of the dynamic changes in functional cerebral oxidative metabolism from tissue mitochondria to blood oxygen. J Cereb Blood Flow Metab 32:745–758. doi:10.1038/jcbfm.2011.198
Viswanathan A, Freeman RD (2007) Neurometabolic coupling in cerebral cortex reflects synaptic more than spiking activity. Nat Neurosci 10:1308–1312. doi:10.1038/nn1977
Volgushev M, Vidyasagar TR, Chistiakova M, Yousef T, Eysel UT (2000) Membrane properties and spike generation in rat visual cortical cells during reversible cooling. J Physiol 522(Pt 1):59–76
Wang H, Wang B, Normoyle KP, Jackson K, Spitler K, Sharrock MF, Miller CM, Best C, Llano D, Du R (2014) Brain temperature and its fundamental properties: a review for clinical neuroscientists. Front Neurosci 8:307. doi:10.3389/fnins.2014.00307
Xu G, Perez-Pinzon MA, Sick TJ (2003) Mitochondrial complex I inhibition produces selective damage to hippocampal subfield CA1 in organotypic slice cultures. Neurotox Res 5:529–538
Yager JY, Asselin J (1996) Effect of mild hypothermia on cerebral energy metabolism during the evolution of hypoxic-ischemic brain damage in the immature rat. Stroke 27:919–925 discussion 926
Yaron-Jakoubovitch A, Koch C, Segev I, Yarom Y (2013) The unimodal distribution of sub-threshold, ongoing activity in cortical networks. Front Neural Circuits 7:116. doi:10.3389/fncir.2013.00116
Yenari M, Kitagawa K, Lyden P, Perez-Pinzon M (2008) Metabolic downregulation: a key to successful neuroprotection? Stroke 39:2910–2917. doi:10.1161/STROKEAHA.108.514471
Yona G, Meitav N, Kahn I, Shoham S (2016) Realistic numerical and analytical modeling of light scattering in brain tissue for optogenetic applications(1,2,3). eNeuro 3. doi:10.1523/ENEURO.0059-15.2015
Acknowledgements
The Carle Neuroscience Institute supported the work. D.A.L. was supported by DC013073. The authors thank Dr. Eugene Kiyatkin (NIH), Dr. Robert Gennis (University of Illinois), Dr. Sanjiv Sinha (University of Illinois), Dr. Naoum Issa (University of Chicago), Dr. Jan Ramirez (Seattle Children’s Hospital), and Dr. Alfredo Garcia (Seattle Children’s Hospital) for their suggestions.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Rights and permissions
About this article
Cite this article
Ibrahim, B.A., Wang, H., Lesicko, A.M.H. et al. Effect of temperature on FAD and NADH-derived signals and neurometabolic coupling in the mouse auditory and motor cortex. Pflugers Arch - Eur J Physiol 469, 1631–1649 (2017). https://doi.org/10.1007/s00424-017-2037-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00424-017-2037-4