Suppressed Neuronal Activity and Concurrent Arteriolar Vasoconstriction May Explain Negative Blood Oxygenation Level-dependent Signal

Overview

Journal J Neurosci

Specialty Neurology

Date 2007 Apr 20

PMID 17442830

Citations 202

Authors

Anna Devor

Peifang Tian

Nozomi Nishimura

Ivan C Teng

Elizabeth M C Hillman

S N Narayanan

Istvan Ulbert

David A Boas

David Kleinfeld

Anders M Dale

Affiliations

Soon will be listed here.

Abstract

Synaptic transmission initiates a cascade of signal transduction events that couple neuronal activity to local changes in blood flow and oxygenation. Although a number of vasoactive molecules and specific cell types have been implicated, the transformation of stimulus-induced activation of neuronal circuits to hemodynamic changes is still unclear. We use somatosensory stimulation and a suite of in vivo imaging tools to study neurovascular coupling in rat primary somatosensory cortex. Our stimulus evoked a central region of net neuronal depolarization surrounded by net hyperpolarization. Hemodynamic measurements revealed that predominant depolarization corresponded to an increase in oxygenation, whereas predominant hyperpolarization corresponded to a decrease in oxygenation. On the microscopic level of single surface arterioles, the response was composed of a combination of dilatory and constrictive phases. Critically, the relative strength of vasoconstriction covaried with the relative strength of oxygenation decrease and neuronal hyperpolarization. These results suggest that a neuronal inhibition and concurrent arteriolar vasoconstriction correspond to a decrease in blood oxygenation, which would be consistent with a negative blood oxygenation level-dependent functional magnetic resonance imaging signal.

Citing Articles

Investigating the Consistency of Negative BOLD Responses to Combinations of Visual, Auditory, and Somatosensory Stimuli and Their Modulation by the Level of Task Demand.

Nelson W, Mayhew S Hum Brain Mapp. 2025; 46(4):e70177.

PMID: 40047348 PMC: 11883661. DOI: 10.1002/hbm.70177.

Neural correlates of personal space regulation in psychosis: role of the inferior parietal cortex.

Vinke L, Avanaki M, Jeffrey C, Harikumar A, Mow J, Tootell R Mol Psychiatry. 2025; .

PMID: 39900675 DOI: 10.1038/s41380-025-02906-4.

Modeling of Blood Flow Dynamics in Rat Somatosensory Cortex.

Battini S, Cantarutti N, Kotsalos C, Roussel Y, Cattabiani A, Arnaudon A Biomedicines. 2025; 13(1).

PMID: 39857656 PMC: 11761867. DOI: 10.3390/biomedicines13010072.

Revealing excitation-inhibition imbalance in Alzheimer's disease using multiscale neural model inversion of resting-state functional MRI.

Li G, Hsu L, Wu Y, Bozoki A, Shih Y, Yap P Commun Med (Lond). 2025; 5(1):17.

PMID: 39814858 PMC: 11735810. DOI: 10.1038/s43856-025-00736-7.

Transcranial Magnetic Stimulation Inter-Pulse Interval Does Not Influence Corticospinal Excitability to the Biceps Brachii During Submaximal Isometric Elbow Flexion.

Imeson D, Gerditschke L, Brown L, Forman D Eur J Neurosci. 2025; 61(1):e16671.

PMID: 39810291 PMC: 11733025. DOI: 10.1111/ejn.16671.

References

Webber R, Stanley G . Nonlinear encoding of tactile patterns in the barrel cortex. J Neurophysiol. 2003; 91(5):2010-22. DOI: 10.1152/jn.00906.2003. View

Filosa J, Bonev A, Straub S, Meredith A, Wilkerson M, Aldrich R . Local potassium signaling couples neuronal activity to vasodilation in the brain. Nat Neurosci. 2006; 9(11):1397-1403. DOI: 10.1038/nn1779. View

Faraci F, Breese K . Nitric oxide mediates vasodilatation in response to activation of N-methyl-D-aspartate receptors in brain. Circ Res. 1993; 72(2):476-80. DOI: 10.1161/01.res.72.2.476. View

Lindauer U, Villringer A, Dirnagl U . Characterization of CBF response to somatosensory stimulation: model and influence of anesthetics. Am J Physiol. 1993; 264(4 Pt 2):H1223-8. DOI: 10.1152/ajpheart.1993.264.4.H1223. View

Moore C, Nelson S . Spatio-temporal subthreshold receptive fields in the vibrissa representation of rat primary somatosensory cortex. J Neurophysiol. 1998; 80(6):2882-92. DOI: 10.1152/jn.1998.80.6.2882. View

Nishimura N, Schaffer C, Friedman B, Lyden P, Kleinfeld D . Penetrating arterioles are a bottleneck in the perfusion of neocortex. Proc Natl Acad Sci U S A. 2006; 104(1):365-70. PMC: 1765467. DOI: 10.1073/pnas.0609551104. View

Nishimura N, Schaffer C, Friedman B, Tsai P, Lyden P, Kleinfeld D . Targeted insult to subsurface cortical blood vessels using ultrashort laser pulses: three models of stroke. Nat Methods. 2006; 3(2):99-108. DOI: 10.1038/nmeth844. View

Sheth B, Moore C, Sur M . Temporal modulation of spatial borders in rat barrel cortex. J Neurophysiol. 1998; 79(1):464-70. DOI: 10.1152/jn.1998.79.1.464. View

Zonta M, Angulo M, Gobbo S, Rosengarten B, Hossmann K, Pozzan T . Neuron-to-astrocyte signaling is central to the dynamic control of brain microcirculation. Nat Neurosci. 2002; 6(1):43-50. DOI: 10.1038/nn980. View

10.

Derdikman D, Hildesheim R, Ahissar E, Arieli A, Grinvald A . Imaging spatiotemporal dynamics of surround inhibition in the barrels somatosensory cortex. J Neurosci. 2003; 23(8):3100-5. PMC: 6742298. View

11.

Iadecola C . Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004; 5(5):347-60. DOI: 10.1038/nrn1387. View

12.

Devor A, Dunn A, Andermann M, Ulbert I, Boas D, Dale A . Coupling of total hemoglobin concentration, oxygenation, and neural activity in rat somatosensory cortex. Neuron. 2003; 39(2):353-9. DOI: 10.1016/s0896-6273(03)00403-3. View

13.

Pettersen K, Devor A, Ulbert I, Dale A, Einevoll G . Current-source density estimation based on inversion of electrostatic forward solution: effects of finite extent of neuronal activity and conductivity discontinuities. J Neurosci Methods. 2006; 154(1-2):116-33. DOI: 10.1016/j.jneumeth.2005.12.005. View

14.

Grinvald A, Manker A, Segal M . Visualization of the spread of electrical activity in rat hippocampal slices by voltage-sensitive optical probes. J Physiol. 1982; 333:269-91. PMC: 1197248. DOI: 10.1113/jphysiol.1982.sp014453. View

15.

Logothetis N . The neural basis of the blood-oxygen-level-dependent functional magnetic resonance imaging signal. Philos Trans R Soc Lond B Biol Sci. 2002; 357(1424):1003-37. PMC: 1693017. DOI: 10.1098/rstb.2002.1114. View

16.

Mulligan S, MacVicar B . Calcium transients in astrocyte endfeet cause cerebrovascular constrictions. Nature. 2004; 431(7005):195-9. DOI: 10.1038/nature02827. View

17.

Peppiatt C, Howarth C, Mobbs P, Attwell D . Bidirectional control of CNS capillary diameter by pericytes. Nature. 2006; 443(7112):700-4. PMC: 1761848. DOI: 10.1038/nature05193. View

18.

Shmuel A, Yacoub E, Pfeuffer J, Van de Moortele P, Adriany G, Hu X . Sustained negative BOLD, blood flow and oxygen consumption response and its coupling to the positive response in the human brain. Neuron. 2002; 36(6):1195-210. DOI: 10.1016/s0896-6273(02)01061-9. View

19.

Dunn A, Devor A, Bolay H, Andermann M, Moskowitz M, Dale A . Simultaneous imaging of total cerebral hemoglobin concentration, oxygenation, and blood flow during functional activation. Opt Lett. 2003; 28(1):28-30. DOI: 10.1364/ol.28.000028. View

20.

Rancillac A, Rossier J, Guille M, Tong X, Geoffroy H, Amatore C . Glutamatergic Control of Microvascular Tone by Distinct GABA Neurons in the Cerebellum. J Neurosci. 2006; 26(26):6997-7006. PMC: 6673912. DOI: 10.1523/JNEUROSCI.5515-05.2006. View