Frontiers in Human Neuroscience www.frontiersin.org

February 2009 | Volume 3 | Article 2 |

HUMAN NEUROSCIENCE

GENERAL COMMENTARY

published: 24 February 2009doi: 10.3389/neuro.09.002.2009

Wiring and plumbing in the brain

Jean Rossier*

Laboratoire de Neurobiologie CNRS, Ecole Supérieure de Physique et de Chimie Industrielles, 75231 Paris Cedex 05, France.* Correspondence: jean.rossier@espci.fr

A commentary onStimulus-induced changes in blood ﬂow and 2-deoxyglucose uptake dissociate inipsilateral somatosensory cortex.

by Devor A., Hillman, E.M., Tian, P., Waeber, C.,Teng, I.C., Ruvinskaya, L., Shalinsky, M.H., Zhu, H., Haslinger, R.H., Narayanan, S.N.,Ulbert, I., Dunn, A.K., Lo, E.H., Rosen, B.R.,Dale, A.M., Kleinfeld, D., and Boas, D.A.(2008). J. Neurosci. 28, 14347–14357.

Brain metabolism dictates the polarity of astrocyte control over arterioles

by Gordon, G.R.C., Choi, H.B., Rungta, R.L.,Ellis-Davies, G.C.R., and MacVicar, B.A.(2008). Nature 456, 745–750.

Anticipatory haemodynamic signals insensory cortex not predicted by local neu-ronal activity

by Sirotin, Y.B., and Das, A. (2009). Nature,457, 475–479.

No one with common sense would believethat in a house, water movements inpipes could tell you how many lamps areon and how much fuel is used for heat-ing. Surprisingly most neuroscientists areconvinced that in the brain monitoringlocal cerebral blood flow (CBF) what I callplumbing, is a reliable surrogate methodto localize electrical neuronal activity andmonitor metabolic events. This is usually done by functional magnetic resonanceimaging (fMRI) a technique that meas-ures haemodynamic changes. In fMRI,the blood-oxygen-level-dependent (BOLD)signal resulting from the paramagneticproperties of deoxyhaemoglobin in redblood cells is measured with precise localand time resolution. In most neuroimagingfMRI studies, activation of the brain withcognitive tasks or sensory stimuli resultsin a local functional hyperaemia, most of the time accompanied by an increase inthe local field potentials (LFP) (Logothetis,2008). How activation of the brain trans-mutes in functional hyperaemia is the topicof intense debate among neuroscientistswith two hypothesis, the “metabolic” andthe “neurogenic” (Estrada and DeFelipe,1998; Hamel, 2006).The metabolic hypothesis assumes acausal link between neuronal energy demandand the regulation of local CBF. The generalassumption, which is supported by PETfindings showing comparable functionalincreases in blood flow and glucose uptake(Raichle and Mintun, 2006), is that CBF iscoupled to regional glucose utilization, whichin turn is directly related to neuronal activ-ity (Magistretti, 2006). Excitatory neuronalactivity releases glutamate which activatesglia through metabotropic glutamate recep-tors. The activation of glial cells will induceat the same time an increase in the diameterof nearby blood vessels and stimulation of glucose uptake. In this metabolic hypothesis,the activity-dependent regulation of localCBF is a feedback mechanism that does notanticipate possible demand.The metabolic hypothesis was supportedby the original observation by Zonta et al.(2003)that astrocytic endfeet surroundingbrain blood vessels were releasing vasodi-lating substances; since then other observa-tions have shown that astrocytes could alsoprovoke vasoconstrictions. These oppositeobservations were confirmed: activationof astrocytes triggers the formation of ara-chidonic acid that is either converted to20-hydroxyeicosatetraenoic acid (20-HETE)in smooth muscle causing vasocontrac-tion or to prostaglandin E

(PGE

) caus-ing vasodilation. These intriguing ﬁndingsare now explained in an elegant paper of MacVicar’s group where they demonstratethat in slices, the ﬁnal fate of arachidonicacid is guided to the vasodilator PGE

if oxygen levels are low and to vasoconstrictor20-HETE if oxygen levels are high (Gordonet al., 2008).The importance given to p

by this workon astrocytes in brain slices is puzzling. Itis known since the 1986 work of Fox andRaichle (1986)that the increase in CBFinduced by brain activation is not correlatedwith O

metabolism; indeed when neuro-nal activity increases locally in the brain,regional blood ﬂow increases more thanoxygen consumption. Changing experimen-tally pO

does not affect regional increase inCBF during brain activation.Mintun et al.(2001)demonstrated in human volunteersthat the regional increase in CBF during vis-ual activation was not affected by hypoxia.More recently Leithner et al. (2005)haveshown that in the rat, hyperbaric hyperoxy-genation did not affect the regional increaseof CBF induced by functional activation.Anyway relevant or not to the physiologi-cal control of CBF, the work of MacVicar’sgroup has resolved the apparent oppositeeffect observed in slices after the activationof astrocytes.In contrast with the metabolic feed-back hypothesis, the neurogenic hypoth-esis (Estrada and DeFelipe, 1998; Hamel,2006) describes a feedforward mechanismwhere the hyperaemia evoked by cerebralactivation is linked to synaptic signallingrather than to the metabolic needs of thetissue. The neurogenic hypothesis was high-lighted recently by Sirotin and Das (2009) who have found a large haemodynamic sig-nal that could deliver arterial blood to thesensory cortex in anticipation of an increaseof local neuronal activity. In short plumbingcould precede wiring.In alert behaving monkeys, Sirotin andDas have developed a task that minimizedvisual input while preserving trial timing.In a dark room, the animals were requiredto fix their gaze periodically on a tiny fixa-tion point to get a reward. Intrinsic signaloptical imaging and LFP were monitored inthe primary visual cortex while the animalsperformed this task. Even though monkeyswere in virtually total darkness with noexposure to visual stimuli, they expressedrobust unexpected haemodynamic signalsin the visual cortex at the trial frequency.Then, while the animals performed the samefixation task, vigorous visual stimuli werepresented; this visual stimuli added a seconddistinct component to the haemodynamic