New Horizons in Neurovascular Coupling: A Bridge Between Brain Circulation and Neural Plasticity

274 Pages·2016·14.991 MB·English

by  Kazuto Masamoto, Hajime Hirase and Katsuya Yamada (Eds.)

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Hamed Ekhtiari, Tehran, Iran.
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Hajime Hirase, Wako, Japan.
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Contributors
K. Arai
NeuroprotectionResearchLaboratory, Massachusetts General Hospital and
Harvard Medical School, Charlestown, MA, United States
D. Coman
MagneticResonanceResearchCenter(MRRC),YaleUniversity,NewHaven,CT,
United States
N. Egawa
NeuroprotectionResearchLaboratory, Massachusetts General Hospital and
Harvard Medical School, Charlestown, MA, United States
M. Fukuda
University ofPittsburgh,Pittsburgh,PA, United States
P. Herman
MagneticResonanceResearchCenter(MRRC),YaleUniversity,NewHaven,CT,
United States
E.Hillman
KavliInstituteforBrainScience;MortimerB.ZuckermanInstituteforMindBrain
and Behavior, Columbia University, New York, NY, United States
H. Hirase
RIKEN Brain Science Institute,Wako, Saitama, Japan
Y. Hoshi
Institute for Medical Photonics Research,Preeminent MedicalPhotonics
Education &Research Center,Hamamatsu University School of Medicine,
Hamamatsu, Japan
H. Hotta
Tokyo Metropolitan Instituteof Gerontology, Tokyo, Japan
F. Hyder
MagneticResonanceResearchCenter(MRRC),YaleUniversity,NewHaven,CT,
United States
I. Kanno
Molecular Imaging Center,NationalInstitute ofRadiological Sciences, Chiba,
Japan
S.-G. Kim
Center for NeuroscienceImaging Research, Institutefor BasicScience,
SungkyunkwanUniversity, Suwon, SouthKorea
M. Kozberg
ColumbiaUniversity, New York, NY, United States
T.Kurihara
Keio University School ofMedicine, Tokyo, Japan
v
vi Contributors
J. Lok
NeuroprotectionResearchLaboratory;Massachusetts General Hospital and
Harvard MedicalSchool,Charlestown, MA, UnitedStates
K. Masamoto
BrainScience Inspired Life Support ResearchCenter,University of
Electro-Communications, Tokyo, Japan
T. Nishijima
TokyoMetropolitan University, Tokyo, Japan
M. Nuriya
KeioUniversity, Shinjuku,Tokyo, Japan
A.J. Poplawsky
University ofPittsburgh,Pittsburgh,PA, United States
B.G. Sanganahalli
MagneticResonanceResearchCenter(MRRC),YaleUniversity,NewHaven,CT,
UnitedStates
C.Y. Shu
YaleUniversity, NewHaven,CT, United States
H. Soya
University ofTsukuba,Tsukuba,Japan
I. Torres-Aleman
CajalInstitute, Madrid, Spain
K. Yamada
HirosakiUniversity Graduate School of Medicine,Hirosaki, Aomori, Japan
Preface
Theabilityofassessingneuralactivitybymeasuringbraincirculationhasrevolution-
izedthewaywestudythebrain.Sincecerebralhemodynamicscanbemeasurednon-
invasively, ie, without physical damages to the brain, neurovascular coupling has
become the principal means for understandingbrain function asshownby modern
imaging techniques such as positron emission tomography (PET), functional mag-
neticresonanceimaging(fMRI),andnear-infraredspectroscopy(fNIRS).Neverthe-
less,themechanismsunderlyingtheneurovascularcouplinghavebeenstillwrapped
inafascinatingmystery.Recent evidenceshavesuggestedthatneurovascularcou-
plingparticipatesinthemaintenanceofnotonlybrainmetabolismbutalsocentral
nervoussystemplasticity.Inthisvolume,wefeature11reviewarticlesonourlatest
understandings of neurovascular coupling mechanisms as well as physiology from
multiple aspects. The first three chapters provide “A physiological basis of neuro-
vascular coupling,” namely Hotta (Chapter 1), Nuriya (Chapter 2), and Yamada
(Chapter3)putperspectivesonthelatestfindingsinneurogenic,gliogenic,andvas-
culogenic mechanisms of neurovascular coupling, respectively. The second topics
titled “Methodology for measurements ofbrain circulation” are coveredby Kanno
(Chapter 4), Hyder (Chapter 5), Fukuda (Chapter 6), and Hoshi (Chapter 7) who
arguetechnologicalaspectsofneurovascularandneurometabolicimagingtoolsspe-
cifically on the signal source issues in macroscopic and microscopic blood flow
imaging modalities, calibrated and submillimeter-resolution, and fNIRS, respec-
tively.Finally,thelastfourchaptersprovidethelatestviewsontherationaleofneu-
rovascular couplingactivelyparticipating incell-to-cell communication tosupport
neural plasticity in development, exercise, and aging processes, titled “Plastic
changes in neurovascular coupling.” A new conceptual frame of trophic coupling
amongdivergentbraincellsisreviewedfromtheviewpointsofneurovasculardevel-
opmentbyArai(Chapter8)andHillman(Chapter10)andtheircolleagues.Kurihara
(Chapter9)illustrateshowtheneurovascularcouplingdevelopsalongwithhypoxic
signaling in the retina, which isconsidered one of the most accessible areas in the
central nervous system. Moreover, plasticity on neurovascular coupling triggered
byphysicalexercisesisreviewedindepthbyNishijima(Chapter11).Finally,given
thecurrentprogressinthefieldofneurovascularcoupling,weprovideafutureper-
spective: what further progress might lead tobreakthroughs.
KazutoMasamoto
Hajime Hirase
Katsuya Yamada
xv
CHAPTER
1
Neurogenic control
of parenchymal arterioles
in the cerebral cortex
H. Hotta1
TokyoMetropolitanInstituteofGerontology,Tokyo,Japan
1Correspondingauthor:Tel.:[phone]x4343;Fax:[phone],
e-mailaddress:[email protected]
Abstract
Centralneuralvasomotormechanismsactontheparenchymalvasculatureofthebraintoreg-
ulateregionalcerebralbloodflow(rCBF).Amongthediversecomponentsofthelocalneural
circuitsofthecerebralcortex,manymaycontributetotheregulationofrCBF.Forexample,
thecholinergicvasodilativesystemthatoriginatesinthebasalforebrainactsontheneocortex
andhippocampus.Notably,rCBFisreducedintheelderlyandpatientswithdementia.The
vasodilatory response, independent of changes in blood pressure and glucose metabolism
inthebrain,occursintheparenchymalarteriolestoproduceasignificantincreaseincortical
rCBF.Recentstudiesilluminatethephysiologicalroleofthecholinergicvasodilatorsystem
relatedtoneurovascularcoupling,neuroprotection,andpromotionofthesecretionofnerve
growthfactor.Inthisreview,cellularmechanismsandspeciesdifferencesintheneurogenic
controlofvascularsystems,aswellasbenefitsofthecholinergicvasodilatorysystemsagainst
cerebral ischemia- and age-dependent impairment of neurovascular plasticity, are further
discussed.
Keywords
Cerebralcortex,Basalforebrain,Cholinergic,Aging,Neuroprotection
1 INTRODUCTION
Cerebralbloodflow(CBF)isanimportantfactorthatmaintainsbrainfunction,anda
prolonged insufficiency causes degeneration and irreversible impairment of brain
function.Inthebrainparenchyma,thereisawealthofbloodvessels.Approximately
15% of cardiac output flows through the brain that accounts for only 2% of body
weight.VariousmechanismsmaintainCBFtosupportbrainactivity,andoneimpor-
tantmechanismisneuralregulationofthecardiovascularsystem.Aswithanybody
organ,brainbloodflowisdeterminedbyperfusionpressureandvascularresistance.
3
ProgressinBrainResearch,Volume225,ISSN0079-6123,http://dx.doi.org/10.1016/bs.pbr.2016.03.001
©2016ElsevierB.V.Allrightsreserved.
4 CHAPTER 1 Neurogenic control of parenchymal arterioles
Thebaroreceptorreflex,mediatedbytheautonomicnervoussystemconnectingthe
heartandperipheralvasculature,preventsexcessivedecreasesinbloodpressureto
ensureasufficientbloodsupplytothebrain.Thebrainvasculaturecanalsoreactto
localconditionstoadjustbloodflow.Amajorthirdsourceofvascularcontrolinthe
brainistheneurogeniccontrolofcerebralbloodvesselsgovernedbythesurrounding
vasoactive nerves (Fig. 1).
A Peripheral neural system
Parasympathetic cholinergic nerve Sympathetic nerve
Sphenopalatine ganglion Somatic sensory nerve
Otic ganglion
Pial arteriole
B Subarachnoid space NO Pia matter
Virchow–Robin space
mAChR Interneuron Cerebral
nAChR cortex
ACh
Local
Central Penetrating arteriole neural
circuite
neural
system
Pyramidal
cell
Capillary
Basal forebrain
cholinergic neuron
Subcortical
areas
Serotonergic neuron (raphe nucleus)
Noradrenergic neuron (locus coeruleus)
Glutamatergic neuron (thalamus, etc.)
FIG.1
Neurogeniccontrolofcerebralbloodvessels.(A)Theperipheralneuralsysteminnervates
largeintracranialandpialvesselsonthesurfaceofthebrain.(B)Thecentralneuralsystem
comprisesnervesoriginatinginthebrainthatpassthroughthebrain,reachingthe
parenchymalvessels(penetratingarteriolesandcapillaries).
2 Neurogenic control of intracortical rCBF 5
The neural system controlling cerebral blood vessels is divided into peripheral
andcentralneuralsystems.Theperipheralneuralsystemcomprisesnervesoriginat-
ingintheperipheralgangliaoutsidetheskull,ie,sympatheticandparasympathetic
autonomicandsomaticsensorynerves(GoadsbyandEdvinsson,2002).Theperiph-
eralneuralsysteminnervateslargeintracranialandpialvesselsonthesurfaceofthe
brain(Fig.1A)andissufficientforregulatingoverallbloodflowtothebrain,which
occursintheautonomicvascularregulationofperipheralnerves(eg,sciaticnerve;
Sato et al., 1994).
Incontrast,thecentralneuralsystemcomprisesnervesoriginatinginthebrainthat
pass through the brain, reaching the parenchymal vessels (Fig. 1B). Because brain
functions are compartmentalized, regional (r)CBF must be appropriately allocated.
TherCBFcanberegulatedbychangesinthediameterofthepenetratingarteriolethat
connectsthepialarterioleonthesurfaceofthebraintotheintraparenchymalcapillary.
Theactivitiesofparenchymalneuronsoflocalneuralcircuits(seeSection2.1)con-
tributetotheregulationofrCBFinassociationwiththoseofothercells,suchasas-
trocytes (see Nuriya and Hirase, 2016, in this volume), vascular cells, or both (see
Yamada, 2016, in this volume). Cellular organization differs among each area of
thebrainparenchyma,andthemechanismsoflocalregulationofparenchymalblood
vesselsvaryaccordingly.Forexample,onecomponentofthecentralneuralsystemis
thecholinergicvasodilativesystemthatoriginatesinthebasalforebrainandactsspe-
cificallyonthecortexandhippocampusthatisvulnerabletotransientischemia,aging,
andneurodegenerativediseases(SatoandSato,1992).Thevasodilativeresponse,in-
dependentofchangesinbloodpressureandglucosemetabolisminthebrain,occursat
theparenchymalpenetratingarterioles(Hottaetal.,2013)tomarkedlyincreasecor-
ticalrCBF.Importantly,thephysiologicalroleofthecholinergicvasodilativesystem
relatedtoneurovascularcoupling(Pich(cid:1)eetal.,2010)andneuroprotection(Hottaetal.,
2002) is also associated with increased secretion of the nerve growth factor (NGF;
Hottaetal.,2007a,2009a).
This review is principally focused on the cholinergic vasodilative system that
originates in the basal forebrain and recent studies related to neural regulation of
the cerebralcortical (partly hippocampal) parenchymal arterioles.
2 NEUROGENIC CONTROL OF INTRACORTICAL rCBF
2.1 LOCAL NEURAL CIRCUITS OF THE CEREBRAL CORTEX
Localneuralcircuitsofthecerebralcortexcomprisepyramidalcells,nonpyramidal
cells, excitatory fibers from other cortical areas and thalamus, and other afferent
fiberssuchascholinergicfibersfromthebasalforebrain(nucleusbasalisofMeynert
[NBM]),serotonergicfibersfromtheraphenucleusofthemidbrain,noradrenergic
fibersfromthelocusceruleus,anddopaminergicfibersfromtheventraltegmental
area(Nieuwenhuysetal.,2008).Manyoftheseneuralcomponentsmaycontributeto
the regulation of rCBF (see reviews of Sato and Sato, 1992; Hillman, 2014).
6 CHAPTER 1 Neurogenic control of parenchymal arterioles
Pyramidal cells are glutamatergic excitatory output cells located in layers II/III,
V,andVI.ExcitatorycellsinlayerIVaremainlyspinystellateandstarpyramidal
cells.Theactivitiesoftheseexcitatoryoutputcellsareregulatedbyinhibitorynon-
pyramidalcellsthroughtheirinhibitoryneurotransmittergammaaminobutyricacid
(GABA).Theseinhibitoryinterneurons,whicharedistributedthroughallsixlayers,
represent approximately 10–30% of the neuronal population (the percentages vary
amongcorticallayers,areas,andspecies)andareclassifiedintodifferentsubtypes
basedonmorphology(eg,basket,chandelier,andMartinotticells),firingcharacter-
istics (eg, fast or irregular spiking), and expression of specific molecular markers
(eg, vasoactive intestinal peptide [VIP], parvalbumin, and somatostatin [SOM];
Fig. 2)(DeFelipeet al., 2013;Kubota et al., 2011).
yer I AAc CR VIP
a NNOOSS
L
PV SOM VVIIPP CR
(VVA binding)
er II/III NPY CRF
y c
a A
L A CCK
NNOOSS
SPR
NOS
PV SOM CR
Y
(VVA binding) P
V N
ayer CRF VIP
L SPR
NNOOSS NOS
CCK
PV NPY SOM CR
(VVA binding)
yer VI SPR CRF VIP
La Ac NOS
A
NNOOSS
CCK
FIG.2
SignalingmoleculesexpressedbyGABAergiccellsinthefrontalcortex.Therelative
numberofcellsthatexpresseachmoleculeisproportionaltothesizeoftheboxineachlayer.
Deep(grayintheprintversion)andlightblue(lightgrayintheprintversion)indicate
strongandweakNOSexpression,respectively(Kubotaetal.,2011).
2 Neurogenic control of intracortical rCBF 7
2.2 CHANGES IN rCBF INDUCED BY THE ACTIVITY OF CORTICAL
NEURONS
TheelectricalactivityofthebraincorrelatesstronglywithchangesinrCBF,andsub-
threshold synaptic processes correlate more closely to rCBF than the spike rates of
principal neurons (Lauritzen et al., 2012; see Fukuda et al., 2016, in this volume).
Whenpyramidalcellsareselectivelyactivatedbyoptogeneticstimulation,synapticac-
tivity(localfieldpotential)andactionpotentials(multiunitactivity)aretightlyrelated
tohemodynamicsignals(Jietal.,2012).AnincreaseincorticalrCBFinmice,induced
by optogenetic stimulation of pyramidal cells, is reduced by a cyclooxygenase-2
(COX2) inhibitor, suggesting that COX2-generated prostaglandin E2 produced by
pyramidal neurons contributes to neurovascular coupling in the cortex (Lacroix
etal.,2015).
AmongvarioussubtypesofcorticalGABAinterneurons(Fig.2),specificsubsets
controlparenchymalvesseldiameter(Caulietal.,2004).Inslicesofbrainharvested
fromneonatalrats,bloodvesselsintheplanefromlayersI–IIIwithdiametersrang-
ing from 5 to 30mm were selected, and single interneurons (layers I–III) within
40mmofthe selected vesselwere recorded inwhole-cell configuration. Thefiring
of single interneurons ((cid:1)8Hz induced by current for 30 or 120s) either dilates or
constricts neighboring microvessels in 13/149 neurons tested. The 13 interneurons
weresubjectedtosingle-cellreversetranscriptase-multiplexpolymerasechainreac-
tionanalysis,andthedatashowthatinterneuronsthatinduceddilatationexpressVIP
or nitric oxide synthase (NOS), whereas SOM is expressed by those that induce
contraction.Further,theresultsofinvivoexperimentsshowthatdirectoptogenetic
activation of cortical inhibitory neurons increases local rCBF (Anenberg et al.,
2015).Inmicethatexpresschannelrhodopsin-2inGABAergicneurons,optogenetic
cortical stimulation greatly attenuates spontaneous cortical spikes, whereas laser
specklecontrastimagingrevealedthatbloodflowisincreased.Theoptogenetically
evokedrCBFresponsesarenotaffectedbyapplicationtothecortexofglutamatergic
(NBQXandMK-801)andGABA-Areceptor(picrotoxin)antagonists.Theseresults
suggestthatactivationofcorticalinhibitoryinterneuronsmediateslargechangesin
blood flow independent of ionotropic glutamatergic or GABAergic synaptic trans-
mission,likelyby releasingcoexpressed vasoactive transmitters.
2.3 CHOLINERGIC VASODILATION INDUCED BY AFFERENT FIBERS
FROM THE BASAL FOREBRAIN
StimulationofbasalforebraincholinergicnucleiproducesanincreaseinrCBFinthe
cortical parenchyma through the activation of muscarinic (mAChR) and nicotinic
(nAChR) cholinergic receptors within the blood–brain barrier (BBB; Biesold
et al., 1989). Further, synthesis of nitric oxide (NO) is essential for this response
(Adachietal.,1992b;Raszkiewiczetal.,1992).Thesignificantincreaseincortical
rCBFduringbasalforebrainstimulation,independentofchangesinsystemicblood
pressure,isuncoupledfromcorticalglucosemetabolisminanesthetized(Hallstr€om