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“This is he pee e iewed e sion o he ollowing a icle: He e o, L., Pa doe, J.,
Ce mina a, N.L. and Apps, R. (2012), Spa ial localiza ion and p ojec ion densi ies o
b ains em mossy ib e a e en s o he o elimb C1 zone o he a ce ebellum. Eu opean
Jou nal o Neu oscience, 35: 539-549, which has been published in inal o m a
h ps://doi.o g/10.1111/j.1460-9568.2011.07977.x . This a icle may be used o
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The ela ionship be ween medulla y mossy ib e a e en s
and he o elimb C1 zone o he a ce ebellum.
Jou nal:
Eu opean Jou nal o Neu oscience
Manusc ip ID:
D a
Manusc ip Type:
Resea ch Repo
Da e Submi ed by he
Au ho :
n/a
Comple e Lis o Au ho s:
He e o, Luis; Uni e si y o B is ol, School o Physiology and
Pha macology; Uni e si y o Se ille, Physiology
Pa doe, Joanne; Uni e si y o B is ol, School o Physiology and
Pha macology
Ce mina a, Nadia; Uni e si y o B is ol, School o Physiology and
Pha macology
Apps, Richa d; Uni e si y o B is ol, School o Physiology and
Pha macology
Key Wo ds:
B ains em, ac - acing, igeminal, cunea e, e icula o ma ion
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Jou nal Sec ion: Neu osys ems
Associa e Edi o : Paul Bolam
The ela ionship be ween medulla y mossy ib e a e en s and he
o elimb C1 zone o he a ce ebellum.
Luis He e o1,2, Joanne Pa doe1,3 Nadia L Ce mina a1 and Richa d Apps1.
1School o Physiology and Pha macology, Medical Sciences Building, Uni e si y o
B is ol, B is ol BS8 1TD, UK
2Depa amen o de Fisiologia, Facul ad de Biologia, Uni e sidad de Se illa, 41012
Se illa, Spain
3Glaxosmi hkline Resea ch and De elopmen , Pa k Road, Wa e, He o dshi e, SG12
0DP, UK
Numbe o pages: 34
Numbe o Figu es: 5
Numbe o Tables: 4
Numbe o wo ds in he whole manusc ip : 8031
Numbe o wo ds in he abs ac : 232
Numbe o wo ds in he in oduc ion: 512
Running i le: Mossy ib e inpu s o C1 ce ebella zone.
Keywo ds: b ains em, ac - acing, cunea e, igeminal, e icula o ma ion
Co esponding au ho :
P o . Richa d Apps
School o Physiology and Pha macology
Medical Sciences Building
Uni e si y o B is ol
B is ol BS8 1TD, UK
[email p o ec ed]
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ABSTRACT
The p esen s udy uses a combined elec ophysiological and double e og ade
ace echnique in a s o examine he spa ial localiza ion and pa e n o axonal
b anching in mossy ib es a ising om h ee majo sou ces in he medulla – he ex e nal
cunea e nucleus, senso y igeminal nucleus, and he e icula o ma ion – o wo
os ocaudally sepa a ed pa s o he ce ebella co ex ha a e linked by common
climbing ib e inpu , he o elimb- ecei ing pa s o he C1 zone in lobulus simplex and
he pa amedian lobule. In each expe imen a small injec ion o hodamine- agged beads
was injec ed in o one co ical egion and an injec ion o luo escein- agged beads was
injec ed in o he o he egion. The main indings we e: 1) he p opo ion o double-
labelled cells in each o he h ee p ece ebelle sou ces o mossy ib es was posi i ely
co ela ed o hose in he in e io oli e. And 2) he C1 zone in lobulus simplex was
ound o ecei e a g ea e densi y o p ojec ions om all h ee sou ces o mossy ib es
han he C1 zone in he pa amedian lobule. These da a a e consis en wi h he ce ebella
one-map hypo hesis since wo os ocaudally sepa a ed, bu soma o opically
co esponding, pa s o he C1 zone ecei e common mossy ib e and climbing ib e
inpu s. Howe e , he di e ences in p ojec ion densi ies also sugges a modi ica ion o
he hypo hesis in ha he wo pa s o he zone di e in he ex en o which hey ecei e
mossy ib e signals a ising om he same p ece ebella nuclei.
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INTRODUCTION
In e ac ion be ween mossy ib e and climbing ib e a e en s a he le el o he
co ex is hough o be cen al o ce ebella mechanisms con ibu ing o mo emen
coo dina ion and mo o lea ning p ocesses. I is he e o e impo an o unde s and hei
ana omical ela ionships (Voogd and Glicks ein, 1998; Apps and Ga wicz, 2005; I o,
2005). Climbing ib es a ise exclusi ely om he con ala e al in e io oli e and make
di ec synap ic con ac wi h Pu kinje cells whose axons p ojec , in u n, o he ce ebella
and la e al es ibula nuclei. As a unc ion o oli oce ebella opog aphy, he ce ebella
co ex is a anged in o a numbe o na ow longi udinally-o ien ed zones (designa ed
om medial o la e al as A, X, B, C1, C2, C3 and D1, D0 and D2, e.g. Voogd and
Biga e, 1980; Buisse e -Delmas and Angau , 1993; Apps and Hawkes, 2009).
Fu he mo e, oli oce ebella axons b anch p e e en ially in he os ocaudal axis; ha is,
a single oli e cell p ojec s o se e al Pu kinje cells loca ed a di e en os ocaudal
poin s in a single longi udinal zone (A ms ong e al., 1973; Apps, 2000; Sugiha a e al.,
2001). This ana omical o ganiza ion indica es ha os ocaudally sepa a e egions o
ce ebella co ex ha e a leas some common climbing ib e inpu .
By con as , mossy ib es a ise om many di e en sou ces, including he spinal
co d, pons and medulla. These inpu s end o e mina e bila e ally wi hin he ce ebella
co ex and show a complex pa e n o b anching wi h a wide mediola e al sp ead, bu
wi h a endency o o m mul iple, os ocaudally-o ien ed s ipes (e.g. Wu e al., 1999;
G a el and Hawkes, 1990; Ruig ok e al, 1995; Se apide e al., 2001; Voogd e al.,
2003).
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The opog aphical ela ionship be ween mossy ib e and climbing ib e
e mina ions in he ce ebella co ex has p e iously been s udied using chole a oxin o
map pa e ns o colla e al b anching (Voogd e al., 2003; Pijpe s e al., 2006; Pijpe s
and Ruig ok, 2006); howe e , ew double e og ade ace s udies ha e conside ed he
spa ial o ganiza ion o cells wi hin p ece ebella sou ces o mossy ib es and hei
ela ionship o os ocaudally sepa a ed pa s o indi idual ce ebella zones.
Expe imen s o da e ha e ocussed on he p ojec ions om he basal pon ine nuclei
(BPN) and la e al e icula nucleus (LRN; King e al., 1998; He e o e al., 2002). In
pa icula , He e o e al., (2002) ound a posi i e ela ionship be ween oli a y and LRN
inpu s a ge ing he o elimb- ela ed pa s o he C1 zone in lobulus simplex (LS) and
he pa amedian lobule (PML), bu no such ela ionship wi h he p ojec ion om BPN.
The e o e i appea s ha he LRN p ojec ion is zonally o ganised, bu he BPN
p ojec ion is no . I emains unclea whe he o no o he sou ces o mossy ib es a e
also zonally o ganised. I such a ela ionship exis s hen his would suppo he one-map
hypo hesis, which pos ula es ha he mossy ib e and climbing ib e a e en sys ems
ha e a common spa ial o ganiza ion (Apps and Hawkes, 2009). The aim he e o e o he
p esen s udy was o in es iga e he opog aphy o mossy ib e p ojec ions o he C1
zone in os ocaudally sepa a ed pa s o he ce ebella co ex (LS and PML), a ising
om h ee majo sou ces o mossy ib e inpu in he medulla: he ex e nal cunea e
nucleus (CN), he senso y igeminal nuclei (STN), and he medulla y e icula
o ma ion (RF).
MATERIALS AND METHODS
All expe imen s we e ca ied ou in acco dance wi h he Uni ed Kingdom
Animals (Scien i ic P ocedu es) Ac o 1986 and we e ca ied ou on 7 male adul
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Wis a a s (255-360 g). Fi e o he expe imen s ha e been analyzed p e iously o
ano he pu pose by Pa doe and Apps (2002) and He e o e al., (2002). All su gical
p ocedu es we e ca ied ou asep ically and we e pe o med wi h su gical le els o
gene al anaes hesia (sodium pen oba bi one injec ed in ape i oneally a an ini ial dose
o 60 mg/kg, Saga al, Rhone Me ieux, Ha low, UK, main enance doses gi en as
equi ed). The do sal su ace o he ce ebellum was exposed in he egion o he
pa a e mal co ex in LS and he PML. The ec al empe a u e o he animal was
moni o ed and kep wi hin physiological limi s using a he mos a ically-con olled
elec ic blanke .
T ace injec ions and his ological p ocessing
Elec ophysiological echniques we e used o guide he ace injec ions. In b ie ,
sho la ency (~12 ms) ield po en ials we e e oked in he C1 zone in bo h LS and PML
as a esul o pe cu aneous elec ical s imula ion (0.1 ms pulse) deli e ed o he
ipsila e al o elimb. In addi ion, elec ical s imula ion (0.1 ms pulse) was deli e ed o
he con ala e al ace and con ala e al o elimb o dis inguish C1 esponses om hose
e oked in neighbou ing zones A2 and C2, espec i ely (see A kins and Apps, 1998 o
u he de ails). Re og ade ace s we e injec ed in o he cen e o he C1 zone, as
de ined by he elec ophysiological mapping, abou 0.3-0.5 mm below he pial su ace.
The ace s we e a suspension o undilu ed la ex mic osphe es agged ei he wi h
hodamine ( ed beads; Luma luo Inc., New Yo k, NY) which was injec ed in o he C1
zone in one lobule, o luo escein- agged la ex mic osphe es (g een beads; Luma luo
Inc., New Yo k, NY) which was injec ed in o he C1 zone in he o he lobule (Apps and
Ruig ok, 2007). Each ace injec ion (a case) was deli e ed hyd aulically ia a glass
mic opipe e a ached o a 1 µl Hamil on sy inge and he o al olume injec ed was
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be ween 50 and 100 nl (see Table 1). Immedia ely a e each injec ion, he pial su ace
was lushed wi h wa m saline hen co e ed wi h gel oam. The c anio omy was sealed
wi h den al ac ylic cemen be o e he wound was closed in laye s. A e eco e y, each
animal was ca e ully moni o ed unde e e ina y guidance h oughou a su i al pe iod
o 7 days. As a p ecau iona y measu e pos -ope a i e analgesia was main ained o 24
hou s wi h bup eno phine (Temgesic, 0.1 mg/kg, i.m., Recki and Colman, Hull, UK),
al hough none o he animals showed any signs o discom o o dis ess du ing he
su i al pe iod. A he end o he su i al pe iod, he a s we e e-anaes he ised wi h
ba bi u a e (200 mg/kg, i.p.) and pe usion- ixed ansca dially wi h 500 ml o
hepa inised saline, ollowed by 1 li e o 4% pa a o maldehyde hen 500 ml o 10%
suc ose in phospha e bu e . The ce ebellum and unde lying b ains em we e emo ed
and s o ed o e nigh a 4°C in 10% suc ose, phospha e bu e solu ion.
The ce ebellum and medulla oblonga a we e sepa a ed and a eezing mic o ome
used o cu he medulla in o 50 µm ans e se sec ions and he ce ebellum in o 50 µm
sagi al sec ions. All sec ions we e moun ed on o gela in-coa ed slides and sepa a ed
in o wo se ies: one o mapping, he o he as a ese e. Slides we e allowed o ai d y
and s o ed in he da k a 4°C wi hou clea ing o co e slipping o minimise ading o
luo escen ma e ial (Apps and Ruig ok, 2007). The sec ions we e examined wi h a
Leica DMRB mic oscope i ed wi h a 50W-me cu y UV ligh sou ce (Ploemopak) and
high nume ical ape u e objec i es (PL Fluo a ). The ed luo escence was iewed wi h
an N2.1 il e block (Dich oic mi o 580 nm, BP 515-560 nm, LP 580 nm), while he
g een luo escence was iewed wi h an H3 il e block (Dich oic mi o 510 nm, BP
420-490 nm, LP 520 nm). Cell bodies e og adely labelled wi h ed and/o g een beads
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we e eadily di e en ia ed om backg ound by he b igh g anula appea ance o he
luo escen labelling in hei cy oplasm.
Analysis o injec ion si es and e og ade labelling
Each injec ion si e consis ed o a co e, con aining a high densi y o luo escen
ma e ial, su ounded by an a ea o much lowe densi y. A scale d awing was made o
each sagi al sec ion con aining he injec ion si e co e, and he leng h o he injec ion
si e co e a he Pu kinje cell laye was measu ed o ob ain i s os ocaudal ex en in ha
sec ion. All he alues om each sec ion con aining he co e we e hen added oge he
and he o al a ea o co ex in ol ed in he injec ion si e was calcula ed by mul iplying
his alue by he sec ion in e al (in his case 0.1 mm). The alues ob ained we e used
o calcula e p ojec ion densi ies (see Table 4). In addi ion, a s anda d se ies o 24
ans e se maps (le els) was cons uc ed (0.2 mm apa ), co e ing he os ocaudal
ex en o he medulla. Each sec ion in one se ies was assigned o one o he ans e se
le els ( ypically 3 sec ions pe le el), and numbe s o e og adely labelled cells and
a eas occupied by cell labelling in he CN, STN and RF we e calcula ed om hese
maps. Howe e , o he pu poses o illus a ion, only one in h ee le els a e depic ed in
he Figu es (i.e. he in e al be ween he le els shown is 0.6 mm), bu his includes he
ull os ocaudal ex en o le els in which e og adely labelled cells we e ound.
Because o sampling, he o al numbe o obse ed labelled cells was an
unde es ima e o he eal numbe o labelled cells. The “ aw” coun s we e he e o e
co ec ed, assuming ha he eal numbe o cells (N ) is a unc ion o he obse ed
numbe o cells (No), he sec ion hickness (50 µm), he numbe o se ies o sec ions
( wo) and pa icle diame e , acco ding o he ollowing equa ion (Abe c ombie, 1946):
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we e signi ican ly g ea e han o PML by a ac o anging be ween 2 o 4:1 (pai ed -
es , wo- ailed, p<0.05), wi h he excep ion o he ipsila e al STN and ipsila e al CN.
Climbing ib es e sus mossy ib es
To de e mine i he e was any zonal o ganiza ion in he mossy ib e p ojec ion
om CN, STN and RF o he C1 zone in LS and PML, o each case he pe cen age o
o e lap o he wo popula ions o single-labelled cells in each o he medulla y nuclei
was compa ed wi h he pe cen age o o e lap o he wo co esponding popula ions o
single-labelled cells in he in e io oli e. Fo p ojec ions o bo h lobules, a highly
s a is ically signi ican posi i e co ela ion was ound o all h ee nuclei, CN ( 2=0.91;
p=0.0003, n=8, Fig. 4A), STN ( 2=0.88; p=0.0005, n=8, Fig. 4B) and RF ( 2=0.89;
p=0.0004, n=8, Fig. 4C). These da a imply ha he deg ee o spa ial o e lap be ween
he CN, STN and RF p ojec ions o he C1 zone in LS and PML is p opo ional o he
in ol emen o common oli a y inpu s o os ocaudally sepa a ed pa s o he same
zone. Consis en wi h his sugges ion, he pe cen age o double-labelled cells in he
di e en p ece ebella sou ces o mossy ib es (exp essed as a pe cen age o he o al
numbe o labelled cells) inc eased wi h he pe cen age o double-labelled cells in he
in e io oli e ( 2=0.67; p=0.001; n=12; Fig. 4D).
DISCUSSION
The p esen s udy in es iga ed he pa e n and quan i y o mossy ib e inpu s o
wo os ocaudally sepa a ed, bu soma o opically co esponding, pa s o he ce ebella
co ical C1 zone in LS and PML. The majo indings we e: (i) mossy ib e p ojec ions
om he CN, STN and RF a e all zonally o ganized; and (ii) he p ojec ion densi ies
om hese p ece ebella nuclei o he C1 zone in LS a e signi ican ly g ea e han hose
o PML by a ac o o app oxima ely 3:1.
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Compa ison wi h p e ious ana omical s udies
Cunea e p ojec ions
The p esen s udy ound li le o no cell labelling in he main cunea e nucleus bu
ins ead e og ade cell labelling was consis en ly p esen wi hin i s ex e nal subdi ision.
The la e elays skin and p op iocep i e inpu s om he neck and ipsila e al o elimb o
he ce ebellum (Campbell e al., 1974; Quy e al., 2011). A p ojec ion o he ‘ o elimb-
ecei ing’ egions o he PML and LS migh he e o e be expec ed. A bila e al
p ojec ion wi h a hea y ipsila e al p edominance is also consis en wi h p e ious
an e og ade (Ge i s e al., 1985; Massopus e al., 1985; Jasmin and Cou ille, 1987a,b;
Päällysaho e al., 1991; Tolbe and Go ing, 1998; Ji and Hawkes, 1994) and e og ade
ace s udies (Rin ik and Walbe g, 1975; Cheek e al., 1975; Somana and Walbe g,
1980; Be e a e al., 1991; Quy e al., 2011), as is ou inding ha labelled cells we e
loca ed mainly in caudal pa s o CN (Rin ik and Walbe g, 1975; Ge i s e al., 1985;
Quy e al., 2011).
P e ious an e og ade mapping s udies ha e also shown a os ocaudally s iped
pa e n o e mina ion om CN o pa a e mal and la e al egions o ce ebella co ex
(Massopus e al., 1985; Tolbe and Go ing, 1998; Ge i s e al., 1985; Jasmine and
Cou ille, 1987a, b; Quy e al., 2011). The p esen s udy ex ends hese p e ious
indings by showing ha CN p ojec ions a e also ela ed o climbing ib e zonal
o ganiza ion. P ojec ion densi ies om CN ha e no p e iously been in es iga ed,
excep in he double e og ade ace s udy by Be e a e al., (1991). In hei s udy,
la ge injec ions we e made in o an e io and pos e io lobes o he ce ebellum in a
(p esumably in ol ing mul iple zones in pa a e mal/la e al pa s o he co ex), and he
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p ojec ion o he an e io lobe was ound o be mo e ex ensi e han o he pos e io lobe
by a ac o o 2:1 This is consis en wi h ou indings in which cells in CN p ojec ing o
LS we e wice as ex ensi e as hose a ge ing PML. Howe e , Be e a e al. (1991)
ound ha 14% o all labelled cells in CN we e double-labelled, whe eas in ou s udy
only 3.2% o all labelled cells we e double-labelled. Taken oge he wi h he indings o
Be e a e al., (1991), one possible in e p e a ion is ha a pa a e mal/la e al zones
loca ed in mo e os al pa s o he co ex ecei e a highe densi y o p ojec ions om
CN han he same zones loca ed in mo e caudal lobules, bu ha some zones ha e a
highe p opo ion o axonal b anching. Fu he s udy o o he indi idual zones will be
equi ed o es his possibili y.
Senso y igeminal nucleus
The STN elays p opiocep i e, mechanical, he mal and ol ac o y in o ma ion
om c anio acial s uc u es o a ious cen es in he b ain (Wai e and T acey, 1995).
Amongs hese a e di ec igeminoce ebella p ojec ions. These ha e been s udied
ex ensi ely in a ange o mammalian species, including a . Simila o ou esul s, cells
p ojec ing o he ce ebellum ha e been epo ed in pa s o alis and pa s in e pola is o
he STN (Sil e man and K uge , 1985; Ya im e al., 1996; Phelan and Falls, 1991).
Howe e , in con as o ou indings, Ya im e al., (1996), using WGA-HRP as a
e og ade ace , concluded ha STN does no ha e a p ojec ion o he C1 zone in a .
The disc epancy may a ise because hei wo e og ade ace injec ions in o he C1
zone we e in lobules III and VIII which a e bo h ‘hindlimb- ecei ing’ a eas o he
ce ebella co ex (A kins and Apps, 1997; Jo n ell e al., 2000). Ya im e al., (1996) also
made injec ions o an e og ade ace in o pa s o alis and pa s in e pola is, and in bo h
cases mossy ib e labelling was ound in medial egions o LS whe e he C1 zone is
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loca ed (see hei Fig. 5). Te minal labelling in medial pa s o PML was no ound in
hei s udy, bu gi en ou inding o di e ences in p ojec ion densi y in he os ocaudal
axis his may be due o he di icul y o de ec ing weake /mo e di use e minal
labelling. In he abbi , igeminoce ebella p ojec ions ha e been epo ed o include
he PML (Bukowska e al., 2003, 2006). Fu he mo e, Bukowska and colleagues
p o ided e idence ha he u ula, and os al and caudal pa s o PML ecei e
independen igeminal senso y in o ma ion om neu ones in sepa a e egions o STN.
This is b oadly consis en wi h he p esen inding ha he e a e pa ially independen
igeminal inpu s o LS and PML.
Medulla y e icula o ma ion
The pa ocellula e icula o ma ion is hough o pa icipa e in a ange o o al-
acial beha iou s, including eye blink e lexes (Smi e al., 2006), whisking (Ha ox e
al., 2002), mas ica ion (T a e s e al., 2010) and ocaliza ion (Ju gens and Hage, 2007).
Simila ly, he in e media e e icula nucleus is hough o be in ol ed in gus a o y
beha iou , including licking (Chen e al., 2001; Nasse e al., 2008). To ou knowledge,
he p esen s udy is he i s o epo mossy ib e p ojec ions om hese egions o he
RF o he ce ebella co ex. Ou indings indica e he e a e subs an ial mossy ib e
p ojec ions, pa icula ly o he C1 zone in LS. Indeed, he g ea es p ojec ion densi y o
he C1 zone in LS was om he ipsila e al RF, and his exceeded he p ojec ion o PML
by a ac o o almos 4:1. This implies di e ences in unc ion be ween hese wo
os ocaudally sepa a ed pa s o he same co ical zone.
Figu e 5 summa izes ou p esen indings ega ding p ojec ion densi ies om
CN, STN and RF o he C1 zone in LS and PML and also hose o He e o e al. (2002)
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ega ding he p ojec ions om he BPN, nucleus e icula is egmen i pon is (NRTP) and
he LRN. In a he la ges sou ce o mossy ib es o he C1 zone in LS is BPN, and in
descending o de , LRN, NRTP, RF, CN and STN (ipsila e al and con ala e al
p ojec ions pooled oge he ). By compa ison, he ela i e p opo ions o he p ojec ion
densi ies o he C1 zone in PML a e as ollows: he la ges sou ce o mossy ib es is he
LRN, ollowed by he BPN, CN, NRTP, STN and RF. O e all, he p ojec ion densi ies
om all hese nuclei o LS a e signi ican ly g ea e han o PML. Taken oge he hese
indings he e o e s ongly sugges ha os ocaudally sepa a ed pa s o he same (C1)
zone a e unc ionally dis inc .
Compa ison o physiological s udies
The cu en s udy ocussed on mossy ib e p ojec ions o wo ‘ o elimb-
ecei ing’ pa s o he C1 zone. This soma o opical cha ac e iza ion is based on
e idence ha hese egions o he C1 zone in a , like o he species, espond a sho
la ency o senso y s imuli deli e ed o he ipsila e al o elimb, con eyed ia he spino-
oli oce ebella sys em (A kins and Apps, 1997; Jo n ell e al., 2000; Pa doe and Apps,
2002). Also, single-uni eco ding in awake beha ing ca s has shown ha Pu kinje cells
in he C1 zone in he homologous egion o he ca PML show a p onounced modula ion
in hei discha ge o simple spikes, ime-locked o he cou se o he s ep cycle in he
ipsila e al o elimb (Apps and Lidie h, 1989). This hy hmic discha ge is p esumably
due in pa o pe iphe al eedback om he ipsila e al limb being con eyed by he
cuneoce ebella ac . I is no ewo hy ha his pa e n o modula ion is simila o
lobule V o he an e io lo e bu di e ences a e also p esen (A ms ong and Edgley,
1984; Edgley and Lidie h, 1988). In pa icula , in lobule V he majo i y o Pu kinje
cells ecei e inpu om ai ly es ic ed egions o he o elimb while in PML ecep i e
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ields end o be mo e di use. Thus, di e en os ocaudally sepa a ed pa s o he same
zone, while ha ing a simila ole in he con ol o mo emen may u ilise di e en ypes
and sou ces o a e en eedback (Apps and Lidie h, 1989).
Howe e he o elimb is no he only sou ce o senso y inpu o he C1 zone in
LS and PML. Fo example, o he body egions also p o ide senso y inpu s ia climbing
ib es, including he ace/whiske a ea (Akaike, 1989; Jo n ell el al., 2000) and he neck
and ho ax (Rushme e al., 1980). Indi idual Pu kinje cells in he C1 zone in PML can
also display changes in bo h complex spike and simple spike ac i i y o bo h ace and
o elimb inpu s, showing con e gence o senso y in o ma ion om di e en body pa s
(Wise e al., 2010).
Mossy ib e inpu s end o o m mul iple, os ocaudally-o ien ed s ipes (Wu e
al., 1999; G a el and Hawkes, 1990; Ruig ok e al., 1995; Se apide e al., 2001; Voogd
e al., 2003). Howe e , he soma o opical map in he ce ebella co ex es ablished by
de ailed elec ophysiological in es iga ion o hese mossy ib e inpu s does no seem o
consis o s ipes, bu a he , a mosaic o mul iple ep esen a ions (pa ches) o indi idual
body pa s o o m a ‘ ac u ed soma o opy’ (e.g. Shambes e al., 1978). To econcile
he wo desc ip ions, i has been ecen ly p oposed ha Pu kinje cell s ipes (zones)
could be subdi ided in o smalle uni s ha co espond o small pa ches (Apps and
Hawkes, 2009). Di e en sou ces o mossy ib es displaying di e en p ojec ion
densi ies o he C1 zone in LS and PML migh hen e lec he p esence o di e en
pa ches wi hin he os ocaudal ex en o an indi idual zone. Such an a angemen may
be in ol ed in in eg a ing di e en pa e ns o senso y inpu con eyed by he climbing
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ib e and mossy ib e sys ems o coo dina e skilled mo emen s which in ol e paw- ace-
mou h in e ac ions such as eeding and g ooming (Rushme e al., 1980).
Mossy ib es e sus climbing ib e inpu s: zones and he one-map hypo hesis
The p esen indings ex end ou p e ious s udy (He e o e al., 2002) by
demons a ing ha in addi ion o he LRN, o he sou ces o mossy ib es o he C1 zone
in LS and PML, he CN, STN and RF, also show a posi i e ela ionship be ween he
deg ee o b anching in he oli oce ebella axons. Howe e , no such ela ionship could
be ound be ween oli oce ebella and pon oce ebella p ojec ions (He e o e al., 2002).
As 9 o he cases used in he cu en analysis we e used in ou ea lie s udy, i is
unlikely ha he appa en di e ence be ween he BPN and o he medulla y sou ces o
mossy ib es is due o a limi a ion o me hods used. Ra he , he di e ence may e lec
he ac ha CN, STN and RF (like he in e io oli e and LRN) ecei e subs an ial
soma osenso y inpu s, while BPN ecei es mainly descending inpu s (Apps and T o ,
1997, He e o e al., 2002).
Following ace injec ions in o he C1 zone in LS and PML, he numbe o
double-labelled cells in he h ee medulla y sou ces o mossy ib es as well as he
in e io oli e a ied subs an ially be ween expe imen s. A possible explana ion o his
is he ac ha some, i no all, ce ebella zones can be u he di ided in o mic ozones
(Osca sson, 1979, Ga wicz e al., 1998). Each injec ion si e may ha e occupied di e en
combina ions o mic ozones wi hin he os ocaudally sepa a ed pa s o he C1 zone in
LS and PML. Mic ozones a e de ined by hei common climbing ib e inpu (Osca sson,
1978; Ga wicz e al., 1998). The e o e i ollows ha in double- ace expe imen s a
high p opo ion o double-labelled cells in he in e io oli e would indica e ha simila
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mic ozones ha e been a ge ed by he wo ace injec ions. In he p esen s udy, he
pe cen age o double-labelled cells in he di e en medulla y nuclei inc eased wi h he
pe cen age o double-labelled cells in he in e io oli e. The e was also a s ong posi i e
co ela ion in he pe cen age o o e lap o he e i o ies occupied by he wo
popula ions o labelled cells in he in e io oli e wi h he pe cen age o o e lap be ween
he wo popula ions o labelled cells in he h ee sou ces o mossy ib es. Taken oge he
hese indings he e o e suppo he one-map hypo hesis, which p edic s ha each
mic ozone wi hin a pa icula longi udinal zone ecei es common mossy ib e and
climbing ib e inpu s (Apps and Hawkes, 2009). Howe e , he p esen s udy also shows
he e a e sys ema ic di e ences in mossy ib e p ojec ion densi ies o he C1 zone in LS
compa ed o PML, con as ing wi h simila climbing ib e p ojec ion densi ies om he
in e io oli e o he same zone (Pa doe and Apps, 2002). This sugges s a e inemen o
he one-map hypo hesis, because i he Pu kinje cells a e he sca old du ing
de elopmen ha guide he dis ibu ion o climbing ib e and mossy ib es o o m
longi udinal zones/mic ozones (Apps and Hawkes, 2009), hen os ocaudal di e ences
in p ojec ion densi ies imply ha he sca old accommoda es a a iable synap ic weigh
o mossy ib e inpu s a di e en poin s along he leng h o he same zone/mic ozone.
Acknowledgemen s
We hank Ms Rachel Bisse and Ms Cla e E e a d o he p epa a ion o his ological
ma e ial. This wo k was suppo ed by he Medical Resea ch Council, he Wellcome
T us , and he Spanish Minis e io de Inno ación y Ciencia.
Abb e ia ions
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BPN, basila pon ine nuclei; CN, ex e nal cunea e nucleus; DAO, do sal accesso y
oli e; ION, in e io oli a y nucleus; iRT, in e media e e icula nucleus; LRN, la e al
e icula nucleus; LS, lobulus simplex; NRTP, nucleus e icula is egmen i pon is;
MAO, medial accesso y oli e; pRF, pa ocellula e icula nucleus; PML, pa amedian
lobule; RF, medulla y e icula o ma ion, STN, senso y igeminal nuclei; STNc,
caudal igeminal senso y nucleus; STNi, in e media e igeminal senso y nucleus
ipsila e al; STNo, o al igeminal senso y nucleus;
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Re e ences
Abe c ombie, M. (1946) Es ima ion o nuclea popula ions om mic o ome sec ions.
Ana . Rec., 94, 239-247
Akaike, T. (1989) Elec ophysiological analysis o he igemino-oli o-ce ebella (c u a
I and II, lobulus simplex) p ojec ion in he a . B ain Res., 482, 402-406
Apps, R. (2000) Ros ocaudal b anching wi hin he climbing ib e p ojec ion o
o elimb- ecei ing a eas o he ce ebella co ical C1 zone. J Comp Neu ol., 419, 193-
204.
Apps, R. & and Ga wicz, M. (2005) Ana omical and physiological ounda ions o
ce ebella in o ma ion p ocessing. Na Re . Neu osci., 6, 297-311
Apps, R. & Hawkes, R. (2009) Ce ebella co ical o ganiza ion: a one-map hypo hesis.
Na . Re . Neu osci., 10, 670-681
Apps, R. & Lidie h, M. (1989) Simple spike discha ge pa e ns o Pu kinje cells in he
pa amedian lobule o he ce ebellum du ing locomo ion in he awake ca . Neu osci.
Le ., 102, 205-210
Apps, R. & Ruig ok, T.J. (2007) A luo escence-based double e og ade ace s a egy
o cha ing cen al neu onal connec ions. Na . P o oc., 2, 1862-1868
Page 23 o 43
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Eu opean Jou nal o Neu oscience
Fo Pee Re iew
30
Sil e man, J.D. & K uge , L. (1985) P ojec ions o he a igeminal senso y nuclea
complex demons a ed by mul iple luo escen dye e og ade anspo . B ain Res.,
361, 383-388
Smi , A.E., Buisse e , P., Buisse e -Delmas, C. De Zeeuw, C.I., Vande We , F. &
Ze a i-Mailly, F. (2006) Re iculo-collicula and spino-collicula p ojec ions in ol ed in
eye and eyelid mo emen s du ing he blink e lex. Neu osci. Res., 56, 363-371
Somana, R. & Walbe g, F. (1980) A e-examina ion o he ce ebella p ojec ions om
he g acile, main and ex e nal cunea e nuclei in he ca . B ain Res., 186, 33-42
Sugiha a, I., Wu, H.S. & Shinoda, Y. (2001) The en i e ajec o ies o single
oli oce ebella axons in he ce ebella co ex and hei con ibu ion o ce ebella
compa men aliza ion. J. Neu osci., 21, 7715-7723
Tolbe , D.L. & Go ing, J.C. (1997) Quan i a i e analysis o cuneoce ebella
p ojec ions in a s: Di e en ial opog aphy in he an e io and pos e io lobes.
Neu oscience, 80, 359-371
T a e s, J.B., He man, K. & T a e s, S.P. (2010) Supp ession o hi d en icula NPY-
elici ed eeding ollowing medulla y e icula o ma ion in usions o muscimol. Beha .
Neu osci., 124, 225-233
Page 30 o 43
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Fo Pee Re iew
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Voogd, J. & Biga e F. (1980) Topog aphical dis ibu ion o oli a y and co ico-nuclea
ibe s. In Cou ille, J., Mon igni, C.De., Lama e, Y. (eds), The in e io oli a y
nucleus: Ana omy and physiology. New Yo k, Ra en P ess, pp. 207-234
Voogd, J. & Glicks ein, M. (1998) The ana omy o he ce ebellum. T ends Cogn. Sci.,
2, 307-313
Voogd, J., Pa doe, J., Ruig ok, T.J. & Apps, R. (2003) The dis ibu ion o climbing and
mossy ib e colla e al b anches om he copula py amidis and he pa amedian lobule:
cong uence o climbing ib e co ical zones and he pa e n o zeb in banding wi hin he
a ce ebellum. J. Neu osci., 23, 4645-4656
Wai e, P.M.E. & T acey, D.J. (1995) T igeminal senso y sys em. In Paxinos G. (ed),
The a ne ous sys em. Academic P ess, San Diego, pp. 705-724
Wise, A., Ce mina a, N.L., Ma ple-Ho a , D.E. & Apps, R. (2010) Mechanisms o
synch onous ac i i y in ce ebella Pu kinje cells. J. Physiol., 588, 2373-2390
Wu, H.S., Sugiha a, I. & Shinoda, Y. (1999) P ojec ion pa e ns o single mossy ib es
o igina ing om he la e al e icula nucleus in he a co ex and nuclei. J. Comp.
Neu ol., 411, 97-118
Ya im, N., Billig, I., Compoin , C, Buisse e , P. & Buisse e -Delmas, C. (1996)
T igeminoce ebella and igemino-oli a y p ojec ions in a s. Neu osci. Res., 25, 267-
283
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FIGURE LEGENDS
Table 1 Summa y o injec ion si e de ails. Case numbe indica es he animal in ol ed;
R and G e e o ed and g een ace ma e ial, espec i ely. Abb e ia ions: MAO,
medial accesso y oli e; DAO, do sal accesso y oli e.
Table 2 Summa y o e og ade labelled cell coun s in he di e en nuclei s udied.
Double-labelled cell coun s exp essed as a pe cen age o smalle cell popula ion. 1Cell
coun s a e he o als o bo h sides o he b ain; x e e s o no e og ade anspo .
Abb e ia ions: CN, ex e nal cunea e nucleus; STN, senso y igeminal nucleus; RF,
medulla y e icula o ma ion.
Table 3 Rela i e dis ibu ion o e og adely labelled neu ones be ween di e en nuclei
p o iding mossy ib es o he injec ion si es. Ipsila e al (ipsi) and con ala e al (con a)
indica e la e ali y ela i e o he injec ion si e.
Table 4 P ojec ion densi ies calcula ed o he di e en medulla y nuclei. RDL2R and
RDL3R we e excluded because in hese cases i was no possible o eliably calcula e a
si e size due o di icul y in measu ing he leng h o he Pu kinje cell laye wi hin he
injec ion si e co e.
Figu e 1. Loca ion o he injec ion si es. (A) Schema ic map o a sagi al sec ion o he
ce ebellum a he le el o he pa a e mis o show he loca ion o he injec ions si es in
he lobulus simplex (LS) and pa amedian lobule (PML) o an example expe imen . The
d awing also shows he mic oelec odes o eco d ( ec) ce ebella ield po en ials
e oked by ipsila e al o elimb s imula ion o guide he ace injec ions (inj). The
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dashed boxes ep esen he a eas shown in B, C. (B, C) Field po en ials eco ded in LS
and PML ollowing elec ical s imula ion o he ipsila e al o elimb (s ). Each ace is an
a e age o ou sweeps. (D, E) Pho omic og aphs showing he injec ion si es in he LS
and PML. (F) Pho omic og aph showing example o a e og adely labelled cell in he
medulla y e icula o ma ion.
Figu e 2. Dis ibu ion o e og adely labelled cells in he ex e nal cunea e nucleus,
medulla y e icula o ma ion and igeminal senso y nucleus in a ep esen a i e
expe imen (RDL7). Cell labelling plo ed on i e equally spaced ans e se le els o
he medulla (AP le els -11.3 o -13.7) a e injec ion o g een ace in o he C1 zone in
LS and ed ace in o PML. Panel LS +PML shows he o e lapping egions be ween
he wo single-labelled popula ions which co espond wi h a eas in which double-
labelled cells we e obse ed. A ows indica e he dis ibu ion o labelled cells in he
ex e nal cunea e nucleus. In e al be ween le els is 0.6 mm. Abb e ia ions: ION,
in e io oli a y nucleus; iRF, in e media e e icula nucleus; LRN, la e al e icula
nucleus; pRF, pa ocellula e icula nucleus; STNc, caudal igeminal senso y nucleus;
STNi, in e media e igeminal senso y nucleus ipsila e al; STNo, o al igeminal
senso y nucleus; (ipsi) and con ala e al (con a) indica e la e ali y ela i e o he
injec ion si e.
Figu e 3. Pooled da a om all single and double- ace expe imen s. F om le o igh
each plo shows he o al a ea con aining e og adely labelled cells a e single- ace
injec ions in o he C1 zone in LS and single- ace injec ions in o PML, and he
o e lapping a eas o he wo single-labelled cell popula ions in double- ace
expe imen s (LS + PML). The egions con aining labelled cells om a leas h ee
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animals is ep esen ed by black shading. In e al be ween le els is 0.6 mm.
Abb e ia ions as in Figu e 2.
Figu e 4. Rela ionship be ween di e gence om in e io oli e and om medulla y
nuclei o he C1 zone in lobulus simplex and he pa amedian lobule. A ea o o e lap in
he ex e nal cunea e nucleus (A), igeminal senso y nucleus (B) and medulla y e icula
o ma ion (C) be ween he wo single-labelled popula ions (exp essed as a pe cen age o
he o al a ea occupied by bo h LS and PML p ojec ions) plo ed as a unc ion o he
a ea o o e lap be ween he wo single-labelled popula ions in he oli e (exp essed as a
pe cen age o he o al a ea). (D) Incidence o double-labelled cells in he medulla y
nuclei as a unc ion o he p opo ion o double-labelled cells in he in e io oli e (all
exp essed as pe cen ages o he co esponding o al labelled cell coun ).
Figu e 5. Diag am summa ising di e ences in densi y o b ains em mossy ib e
p ojec ions o he C1 zone in lobulus simplex and he pa amedian lobule. Abb e ia ions
as in Figu e 2. BPN, basila pon ine nuclei; NRTP, nucleus e iculus egmen i pon is.
Includes da a om He e o e al (2002).
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Figu e 1. Loca ion o he injec ion si es. (A) Schema ic map o a sagi al sec ion o he ce ebellum a
he le el o he pa a e mis o show he loca ion o he injec ions si es in he lobulus simplex (LS)
and pa amedian lobule (PML) o an example expe imen . The d awing also shows he
mic oelec odes o eco d ( ec) ce ebella ield po en ials e oked by ipsila e al o elimb s imula ion
o guide he ace injec ions (inj). The dashed boxes ep esen he a eas shown in B, C. (B, C) Field
po en ials eco ded in LS and PML ollowing elec ical s imula ion o he ipsila e al o elimb (s ).
Each ace is an a e age o ou sweeps. (D, E) Pho omic og aphs showing he injec ion si es in he
LS and PML. (F) Pho omic og aph showing example o a e og adely labelled cell in he medulla y
e icula o ma ion.
145x132mm (300 x 300 DPI)
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Figu e 2. Dis ibu ion o e og adely labelled cells in he ex e nal cunea e nucleus, medulla y
e icula o ma ion and igeminal senso y nucleus in a ep esen a i e expe imen (RDL7). Cell
labelling plo ed on i e equally spaced ans e se le els o he medulla (AP le els -11.3 o -13.7)
a e injec ion o g een ace in o he C1 zone in LS and ed ace in o PML. Panel LS +PML shows
he o e lapping egions be ween he wo single-
labelled popula ions which co espond wi h a eas in
which double-labelled cells we e obse ed. A ows indica e he dis ibu ion o labelled cells in he
ex e nal cunea e nucleus. In e al be ween le els is 0.6 mm. Abb e ia ions: ION, in e io oli a y
nucleus; iRF, in e media e e icula nucleus; LRN, la e al e icula nucleus; pRF, pa ocellula
e icula nucleus; STNc, caudal igeminal senso y nucleus; STNi, in e media e igeminal senso y
nucleus ipsila e al; STNo, o al igeminal senso y nucleus; (ipsi) and con ala e al (con a) indica e
la e ali y ela i e o he injec ion si e.
195x212mm (300 x 300 DPI)
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Figu e 3. Pooled da a om all single and double- ace expe imen s. F om le o igh each plo
shows he o al a ea con aining e og adely labelled cells a e single- ace injec ions in o he C1
zone in LS and single- ace injec ions in o PML, and he o e lapping a eas o he wo single-
labelled
cell popula ions in double-
ace expe imen s (LS + PML). The egions con aining labelled cells om
a leas h ee animals is ep esen ed by black shading. In e al be ween le els is 0.6 mm.
Abb e ia ions as in Figu e 2.
193x230mm (300 x 300 DPI)
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Figu e 4. Rela ionship be ween di e gence om in e io oli e and om medulla y nuclei o he C1
zone in lobulus simplex and he pa amedian lobule. A ea o o e lap in he ex e nal cunea e nucleus
(A), igeminal senso y nucleus (B) and medulla y e icula o ma ion (C) be ween he wo single-
labelled popula ions (exp essed as a pe cen age o he o al a ea occupied by bo h LS and PML
p ojec ions) plo ed as a unc ion o he a ea o o e lap be ween he wo single-
labelled popula ions
in he oli e (exp essed as a pe cen age o he o al a ea). (D) Incidence o double-labelled cells in
he medulla y nuclei as a unc ion o he p opo ion o double-labelled cells in he in e io oli e (all
exp essed as pe cen ages o he co esponding o al labelled cell coun ).
307x783mm (300 x 300 DPI)
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Figu e 5. Diag am summa ising di e ences in densi y o b ains em mossy ib e p ojec ions o he C1
zone in lobulus simplex and he pa amedian lobule. Abb e ia ions as in Figu e 2. BPN, basila
pon ine nuclei; NRTP, nucleus e iculus egmen i pon is. Includes da a om He e o e al., (2002).
146x228mm (300 x 300 DPI)
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