Therian mammals are characterized by well-differenti-ated superficial facial muscles (also known as muscles offacial expression) derived from the second branchial arch.Compared to nonmammalian vertebrates whose facialmuscle actions are limited to opening and closing theapertures encircling the mouth, eyes, and nostrils, mam-mals are capable of a much more varied range of facialmovements (van Hooff, 1967). Greater mobility of the lipsand cheeks may have evolved in stem mammals to facili-tate neonatal suckling and more extensive chewing of food(Huber, 1930). Additionally, with the evolution of in-creased energetic demands related to homeothermy inmammals, facial muscles may have become differentiatedto facilitate mobility of the external ears and whiskingmovements of tactile vibrissae to explore more actively theenvironment for food items (van Hooff, 1967). Building on
these basic mammalian adaptations within particular lin-eages, subsets of facial muscles have increased in com-
Grant sponsor: the National Science Foundation; Grant num-ber: BCS-0121286; Grant sponsor: the Leakey Foundation; Grantsponsor: the Wenner-Gren Foundation for Anthropological Re-search; Grant sponsor: Mount Sinai School of Medicine; Grantsponsor: Kent State University.
*Correspondence to: Chet C. Sherwood, Department of Anthro-pology, Kent State University, 226 Lowry Hall, Box 5190, Kent,OH 44242. Fax: 330-672-2999. E-mail: [email protected]
Received 16 August 2005; Accepted 17 August 2005DOI 10.1002/ar.a.20259Published online 2 October 2005 in Wiley InterScience(www.interscience.wiley.com).
THE ANATOMICAL RECORD PART A 287A:1067–1079 (2005)
plexity and expanded concomitantly with socioecologicaladaptations. For example, the mass of musculature sur-rounding the blowhole in odontocete cetaceans alters theshape of the spermaceti organ during the emission ofbiosonar (Cranford et al., 1996). In anthropoid primates, anumber of tractor muscles (e.g., zygomaticus major, zygo-maticus minor, levator labii superioris, depressor angulioris, depressor labii inferioris, and risorius) surround themouth to configure the shape of the lips for vocalizationsand facial displays (Huber, 1931). Perhaps the most im-pressive example of facial musculature specialization isthe elongated and highly mobile trunk of elephants, whichis composed of several layers of differentially orientedmuscle bundles derived exclusively from the caninus mus-cle (also known as levator anguli oris) (Endo et al., 2001).
Neurons within the facial motor nucleus (VII) of thebrainstem innervate the superficial facial musculatureand hence comprise the final common output for circuitsrelated to various behaviors, including emotional expres-sion, vocal communication, respiration, ingestion, protec-tive reflexes, and sensory exploration of the environment.In addition to the main VII, the accessory facial nucleus(also called the suprafacial nucleus or the dorsal facialnucleus) contains motoneurons of deep facial muscles (i.e.,stylohyoid and the posterior belly of the digastric). Axonsof motoneurons in the main VII and the accessory facialnucleus exit the brainstem together on the ipsilateral sideas the facial nerve (CN VII), then leave the base of theskull via the stylomastoid foramen and enter the parotidgland, where the main trunk of the facial nerve dividesinto several major branches.
Considering the central involvement of the VII in di-verse sensorimotor adaptations of the facial musclesacross phylogeny, the comparative neurobiology of the VIIis of special interest. This article presents an overview ofphylogenetic variation in the neuroanatomical structureand connectivity of the VII in mammals.
SIMILARITIES ACROSS PHYLOGENYGeneral Cytoarchitectural Plan
The VII is composed predominantly of multipolar �-mo-toneurons (Fig. 1), which express the biochemical markerscholine acetyltransferase (Ichikawa and Hirata, 1990;Ichikawa and Shimizu, 1998; Tsang et al., 2000), nonphos-
phorylated neurofilament protein (Tsang et al., 2000), andcalcineurin (Strack et al., 1996). Morphological and tracttracing studies in rats and cats suggest that the VII con-tains few, if any, interneurons (Courville, 1966a; McCalland Aghajanian, 1979). Injection of horseradish peroxi-dase (HRP) into the main trunk of the facial nerve, forinstance, results in retrograde labeling of 98% of neuronsin the VII, indicating the virtual absence of neurons thatdo not directly innervate facial muscles (McCall and Agha-janian, 1979). In addition, size histograms of facial neu-rons in macaque monkeys (Welt and Abbs, 1990) and rats(Martin et al., 1977) show a unimodal distribution, indi-cating that few small �-motoneurons are found in the VII.This concords with reports that muscle spindles, whichare innervated by �-motoneurons, occur in very low abun-dance in superficial facial muscles (Bowden and Mahran,1956; Olkowski and Manocha, 1973; Dubner et al., 1978;Brodal, 1981; Sufit et al., 1984).
As with other motor nuclei (e.g., hypoglossal) (Sokoloffand Deacon, 1992), the neurons of the VII are arranged insubnuclei that lie adjacent to one another in longitudinalcell columns. Because each subnucleus extends rostrocau-dally for a different distance, the differentiation of subnu-clei is most apparent in coronal sections at the middlethird of the VII. Historically, the number of VII subnucleirecognized by researchers has varied considerably de-pending on species, anatomical methods, and subjectiveassessment. For example, based on Nissl staining pat-terns, Welt and Abbs (1990) described six subnuclei inlong-tailed macaques (Macaca fascicularis), Jenny andSaper (1987) described four subnuclei in M. fasciularis,and Satoda et al. (1987) described five subnuclei in Japa-nese macaques (M. fuscata). Some discrepancy may arisefrom the fact that facial neurons are arranged in irregularclusters and cytoarchitectural boundaries between subnu-clei are not well defined in most species (Papez, 1927;Vraa-Jensen, 1942; van Buskirk, 1945; Courville, 1966a;Dom et al., 1973; Martin and Lodge, 1977; Porter et al.,1989; Welt and Abbs, 1990; Yew et al., 1996; Sherwood etal., 2005). Nonetheless, some boundaries among subnucleican be more clearly delimited in tissue stained for myelinand nonphosphorylated neurofilament protein (Fig. 2). Inthese preparations, however, there is not clear differenti-ation between all the subnuclei identifiable based on cy-toarchitecture, suggesting that there may be fewer func-
Fig. 1. Motoneurons located in the lateral sub-division of the VII of an orangutan (Pongo pyg-maeus) stained for (A) Nissl substance and (B)nonphosphorylated neurofilament protein (NPNFP)with SMI-32 antibody. Scale bar � 100 �m.
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tionally and anatomically distinct subdivisions thanusually recognized. Also, it is interesting that VII subnu-clei in larger-brained species tend to be more completelyseparated by interstitial space as compared to their small-er-brained relatives (Fig. 3). This suggests that there isrelative elaboration of the dendritic arbors of these mo-toneurons as a consequence of scaling rules (Sherwood etal., 2005). These allometric trends may contribute to theappearance of more distinct VII subnuclei in some species;however, the functional significance of such differentia-tion is not known.
Conserved MusculotopyThe topographic representation of the muscles of facial
expression in the VII has been studied in several species.Unfortunately, interpretation of older axotomy studies ishampered by the fact that retrograde cellular pathologicchanges are somewhat unpredictable (Martin and Lodge,1977). In addition, many retrograde cell degenerationstudies involved sectioning of a single peripheral nervebranch. Individual facial nerve branches, however, mayinnervate a number of different muscles and a particularmuscle may be supplied by more than one nerve branch(Provis, 1977). Thus, early studies that found a close cor-respondence between subnuclei of the VII and the inner-vation territories of peripheral branches of the facial nervemay have been influenced by methodological artifact (vanGehuchten, 1898; Marinesco, 1899; Yagita, 1910; Papez,1927; Hogg, 1928; Nishi, 1965; Courville, 1966a), not thetrue anatomical organization of the nucleus.
More recent studies utilizing sensitive retrograde tracttracers such as HRP and fluorescence dyes have providedmore detailed and reliable data on the musculotopic orga-nization of facial motoneurons in several species, includ-ing brush-tailed possums (Provis, 1977), opossums (Domand Zielinski, 1977; Dom, 1982), pigs (Marshall et al.,2005), guinea pigs (Hamner et al., 1989), rats (Watson etal., 1982; Hinrichsen and Watson, 1984; Klein andRhoades, 1985; Klein et al., 1990), mice (Ashwell, 1982;Komiyama et al., 1984; Terashima et al., 1993), rabbits(Baisden et al., 1987; Satoda et al., 1988), macaque mon-keys (Satoda et al., 1987; Porter et al., 1989; Welt andAbbs, 1990; VanderWerf et al., 1997, 1998; Morecraft etal., 2001), capuchin monkeys (Horta-Junior et al., 2004),and cats (Kume et al., 1978; Shaw and Baker, 1985).Taken together, the results of these studies suggest that abasic pattern of muscle representation exists in the VIIthat is common to all mammals (Dom, 1982; Komiyama etal., 1984; Swanson et al., 1999; Horta-Junior et al., 2004;Marshall et al., 2005).
As a rule, the rostrocaudal axis of the facial muscula-ture is represented along the mediolateral axis of the VII,whereas the superoinferior axis of the face is representedalong the dorsoventral axis of the nucleus. Thus, musclessurrounding the mouth are represented in lateral regionsof the VII, posterior auricular and neck muscles are rep-resented in medial regions, and neurons that are locatedintermediate innervate muscles around the eyes, the fore-head, and anterior auricular muscles (Fig. 4). Discreteinjections of retrograde tracers into facial muscles of ma-caques and capuchins (Welt and Abbs, 1990; Horta-Junioret al., 2004) and individual whisker follicle muscles of rats(Klein and Rhoades, 1985) indicate that different regionsof the same facial muscle are represented at all rostrocau-dal levels within the nucleus.
Strong evidence for evolutionary conservation of thismusculotopic plan in the mammalian VII comes from trac-ing experiments in the marsupial North American opos-sum (Didelphis virginiana), which show that despite poordifferentiation among subnuclei, the basic mammalianplan of musculotopic representation is present (Dom,1982). Data from mutant strains such as reeler mice (Ter-ashima et al., 1993) and Shaking Rat Kawasaki (Setsu etal., 2001), furthermore, indicate that the musculotopicorganization of VII is preserved in spite of abnormal mi-gration of facial neuroblasts and atypical VII cytoarchitec-
Fig. 2. Coronal sections through the midbody of the VII in a long-tailed macaque monkey (Macaca fascicularis) showing architecture asrevealed by staining for (A) Nissl substance, (B) myelin, and (C) non-phosphorylated neurofilament protein (NPNFP). Scale bar � 250 �m.
1069FACIAL MOTOR NUCLEUS IN MAMMALS
ture. While it is known that ephrins and hepatocytegrowth factor are important axon guidance cues that di-rect developing motor axons to enter the mesenchyme ofthe appropriate branchial arch (Caton et al., 2000; Kury etal., 2000), the molecules that direct growth cones towardspecific target muscles in the periphery are not yet known(Chandrasekhar, 2004). Based on the similarities in VIImusculotopy across diverse species, however, it wouldseem that the molecular cues that guide axons to targetmuscles in the second branchial arch are evolutionarilyconserved.
While the fundamental topographic organization ofmuscle representation in the VII seems to be similaracross mammals, the precise mapping between peripheralinnervation territories and anatomical subdivisions of thenucleus have not been fully elucidated within any species,let alone across species. It appears, however, that a cer-
tain amount of overlap may exist among motoneuron poolsfor different muscles in the VII. For example, overlappingmotoneuron pools have been described for different peri-oral muscles in pigs (Marshall et al., 2005), orbicularisoculi and the frontalis of rats (Watson et al., 1982), theanterior and posterior auricular levators of bats (Friaufand Herbert, 1985), upper and lower eyelids in cats (Shawand Baker, 1985), and mentalis and orbicularis oris inmacaques (Welt and Abbs, 1990). This contrasts with themore orderly somatotopic representation of mechanore-ceptors in the principal trigeminal sensory nucleus (Bel-ford and Killackey, 1979). However, the apparent inter-mingling of muscle representation may, to some extent, bedue to the experimental artifact of tracer spread to adja-cent muscles. Populin and Yin (1995) have demonstratedextremely specific topography of pinna muscle represen-tation in the mediodorsal subnucleus of the cat VII byusing very small injections (1–2 �l) of cholera toxin B-HRPinto individual pinna muscles. Discrete motoneuron poolshave also been shown to innervate different portions of theorbicularis oculi muscle in rhesus macaques (VanderWerfet al., 1998).
Afferent Connections From Brainstem andMidbrain
Studies, mostly in rodents, have shown that the VIIreceives afferent inputs from diverse brainstem and mid-brain sites, reflecting its role in various complex orofacialbehaviors. In addition, pharmacological and anatomicaldata indicate that the responsiveness of facial motoneu-rons is regulated by several neuromodulatory systems,including serotonin (Takeuchi et al., 1983; Li et al., 1993b;Tallaksen-Greene et al., 1993; Leger et al., 2001; Hattox etal., 2003), substance P (Senba and Tohyama, 1985; Tal-laksen-Greene et al., 1993; Yew et al., 1996), enkephalin(Fort et al., 1989; Yew et al., 1996), and acetylcholine (Fortet al., 1989; Ichikawa and Hirata, 1990; Yew et al., 1996;
Fig. 3. Cytoarchitecture of the VII from mem-bers of the same order that vary in overall size.Order Rodentia: (A) rat (Rattus norvegicus), ap-proximately 2 g brain weight, versus (B) capybara(Hydrochaeris hydrochaeris), approximately 55 gbrain weight; Order Carnivora: (C) domestic cat(Felis silvestris), approximately 35 g brain weight,versus (D) leopard (Panthera pardus), approxi-mately 125 g brain weight. Note that the propor-tionate composition of subdivisions appears simi-lar in members of the same clade; however,subnuclei are more differentiated in the specieswith larger brains. Scale bar � 250 �m.
Fig. 4. Schematic diagram showing the position of muscle represen-tation relative to the VII that can be generalized across mammals.Although there is some consistency in the nomenclature for subnucleiacross studies of the same species, given interspecific variation in theanatomical orientation of the nucleus as a whole, as well as the degreeto which subnuclei are differentiated, existing subnucleus classificationcannot be easily applied to all mammals.
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Ichikawa and Shimizu, 1998; Kus et al., 2003). For exam-ple, the presence of very high densities of 5-HT2 receptorsin the VII suggests that serotonergic facilitation of facialmotoneuron excitability is important in the regulation ofcentral pattern motor generating networks for blink re-flexes, respiration, rhythmic whisking, and mastication(McCall and Aghajanian, 1979; Pazos et al., 1985; Mengodet al., 1990; Rasmussen and Aghajanian, 1990; LeDoux etal., 1998).
Afferent inputs to the VII have been identified originat-ing in the brainstem, including locations throughout thereticular formation, the nucleus ambiguus, hypoglossalnucleus, sensory trigeminal complex, paralemniscal nu-cleus, and parabrachial nucleus (Hinrichsen and Watson,1983; Fay and Norgren, 1997; Pinganaud et al., 1999;Dauvergne et al., 2001; Popratiloff et al., 2001). The med-ullary reticular formation is the greatest source of affer-ents to all orofacial cranial nerve motor nuclei, includingVII (Travers and Norgren, 1983). Tracing studies haveidentified several groups of inhibitory GABA and glycin-ergic premotor neurons in this region, as well as theparalemniscal zone, which project to the VII, trigeminalmotor, ambiguus, and hypoglossal nuclei to coordinatemastication and swallowing (Travers and Norgren, 1983;Li et al., 1997). Some individual neurons in the reticularformation have been shown to possess collateral axonsthat synapse within several different cranial orofacial mo-tor nuclei (Amri et al., 1990; Li et al., 1993a; Popratiloff etal., 2001). It is thought that projections from the sensorytrigeminal complex, particularly the magnocellular por-tion of the subnucleus caudalis, provide sensory feedbackto facial motoneurons involved in whisking movements ofthe vibrissae (Erzurumlu and Killackey, 1979).
The VII also receives projections from the midbrain,including the superior colliculus, red nucleus, periaque-ductal gray, and several nuclei involved in oculomotorcontrol (Courville, 1966b; Martin and Dom, 1970; Mizunoet al., 1971; Edwards, 1972; Yu et al., 1972; Panneton andMartin, 1979, 1983; Hinrichsen and Watson, 1983; Vidal
et al., 1988; Hattox et al., 2002; Dauvergne et al., 2004).Inputs from the red nucleus, which relay cerebellar infor-mation to facial motoneurons (Holstege et al., 1984; Hol-stege and Tan, 1988), may play a role in the fine adjust-ment of nasolabial activity during whisking behaviors(Hinrichsen and Watson, 1983). Orientation of the ears toobjects of interest detected in the visual field may bemediated by superior colliculus inputs to motoneurons ofthe pinnae (Dom et al., 1973; Harting et al., 1973; Kilimovand Milev, 1973). Additionally, the presence of inputsfrom the superior colliculus to palpebrae motoneuronssuggests a substrate for saccade-related lid movements(Vidal et al., 1988; Dauvergne et al., 2004). Collectively,these data illustrate that VII motoneurons integrate anarray of inputs to subserve adaptive behaviors of the oro-facial muscles.
PHYLOGENETIC SPECIALIZATIONSCounts of Facial Neuron Numbers AcrossSpecies
Several studies have reported total neuron number forthe VII in different species (Table 1). It is difficult, how-ever, to compare neuron numbers among species based onthese data because many older studies used assumption-based counting methods. Typically, these studies wereperformed by counting the two-dimensional projected pro-files of neurons from relatively thin histological sections.Because large cells have a greater chance of being sam-pled within such sections, the number of profiles counteddoes not have a simple or known relationship to the totalnumber of cells in a given volume (Thune and Pakken-berg, 2000). Corrections for these biases, such as the Aber-crombie correction, make assumptions about the shapeand orientation of cells that are rarely met by actualbiological objects (Mouton, 2002). As a consequence, inter-group differences in the size, shape, and orientation ofcells can lead to significant bias in results based on thesemethods.
TABLE 1. Counts of VII neuron numbers from previous studies
Species N Mean Range Reference
Homo sapiens 15 — 5,196–6,270 (Maleci, 1934)56 6,811 4,500–9,460 (van Buskirk, 1945)4 12,500 — (Blinkov and Ponomarev, 1965)8 — 6,040–13,640 (Blinkov and Glezer, 1968)
— 6,000 — (Welt and Abbs, 1990)Macaca mulatta 4 4,600 — (Blinkov and Ponomarev, 1965)Macaca fascicularis 12 2,222 1,600–3,043 (Welt and Abbs, 1990)Macaca sp. 4 — 3,875–5,540 (Blinkov and Glezer, 1968)Rattus norvegicus — 5,092 — (Martin et al., 1977)
2 5,576 5,332–5,820 (Watson et al., 1982)Rattus rattus — 4,425 — (Tsai et al., 1993)
2 4,906 — (Friauf and Herbert, 1985)3 3,350 3,178–3,466 (Martin et al., 1977)
Another limitation of existing data on VII neuron num-ber is that only a few distantly related species have beenstudied. Such phylogenetically dispersed data pose com-plications in establishing the relationship between facialneuron number and the evolution of fine motor control offacial movements. Previous comparative studies, for in-stance, found that dogs and cats have more facial neuronsthan primates (van Buskirk, 1945; Blinkov and Pono-marev, 1965). These findings led Blinkov and Ponomarev(1965: p. 299) to conclude that “considerable complicationsof functions is by no means connected with any increase inthe number of neurons in the corresponding motor nucleiof the brain stem.” However, carnivores and primates areseparated by approximately 79–88 million years of inde-pendent evolution (Murphy et al., 2001). The functionalsignificance of differences in neuron numbers becomesobscured in comparisons of such vastly divergent lineages.It is difficult to discern based on these data whether dif-ferences in neuron numbers among mammalian lineagesare adaptive specializations or have been driven to fixa-tion by neutral drift or pleiotropy.
Stereologic Analysis of Facial Neuron Numberin Primates
To address some of these limitations, Sherwood (2003)performed designed-based stereologic analysis of VII neu-ron numbers within a restricted phylogenetic sample in-cluding 18 species of primates and 1 scandentian (Tupaiaglis). The total number of neurons in the left-side VII wasestimated based on Nissl-stained sections using the opti-cal fractionator method (West et al., 1991).
Table 2 shows species mean, coefficient of variation(CV), and coefficient of error (CE) of VII neuron numberestimates. Among primates, species mean VII neuronnumber varied by a factor of 3.2. This relatively minimalrange of variation contrasts with the much wider rangeover which VII volume (23.6-fold) and medulla volume(44.3-fold) vary across the same species (Sherwood et al.,2005). Due to this narrow range and the considerable
amount of intraspecific variation, there was extensiveoverlap in VII neuron number among individuals of dif-ferent taxa (Fig. 5A). Notably, values for many monkeysfell within the range of great apes and humans.
Figure 5B shows the allometric relationship betweenspecies mean VII neuron number and medulla volume1/3
in this sample. Overall, the relationship between thesevariables is only moderately strong (r2 � 0.566; P � 0.001;n � 16) and many species deviate substantially from ex-pectations based on the regression function. Of particularinterest is that the greatest departure from predicted VIIneuron numbers is Aotus trivirgatus, which have 42%more VII neurons than predicted for a primate of theirmedulla size (studentized deleted residual � 2.33). It is
TABLE 2. Total number of VII neurons estimated bythe optical fractionator
Fig. 5. A: The results of optical fractionator estimates of total neuronnumber in VII. B: The double-logarithmic least-squares (LS) regression ofVII neuron number on medulla volume1/3 is shown. The LS line is fit to alldata and the great ape and human points are depicted as closed circlesfor comparison. Values for species mean medulla volume were obtainedfrom Sherwood et al. (2005). Because Shapiro Wilk’s W-tests showedthat variables were not normally distributed, regression analyses usedlogarithmic (base 10) transformed data. The cube root of medulla volumewas used to adjust volumetric measures to the same dimensionality asneuron number.
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noteworthy that owl monkeys are active in a nocturnalenvironment and consequently do not rely extensively onthe visual channel for social communication (Moyniham,1967). In this regard, they have among the most poorlydifferentiated facial muscles of any anthropoid (Huber,1931) and they use very few facial expressions in theirsocial communication (Moyniham, 1967). This suggeststhat variation in VII neuron numbers may not be strictlyassociated with facial muscle mobility.
To investigate further a possible relationship with spe-cializations for facial expression, VII neuron numberswere examined for a correlation with social group size totest the hypothesis that relatively greater facial muscleinnervation is necessary in species that live in large gre-garious groups that rely on facial displays to mediate theirsocial interactions (Andrew, 1963b). Data on social groupsize obtained from Barton (1999) were used as an index ofsocial complexity (Dunbar, 1992, 1998). To control forphylogenetic bias in the data set, independent contrasts(Felsenstein, 1985; Garland et al., 1999) were calculatedfrom log-transformed species mean data based on the to-pology and untransformed branch lengths from a compos-ite phylogeny of primates (Purvis, 1995). Because con-trasts in VII neuron number were significantly correlatedwith contrasts in medulla volume1/3, VII neuron numbercontrasts were adjusted by calculating residuals from theleast-squares regression line on medulla volume1/3. Groupsize contrasts were not correlated with medulla volume1/3
contrasts and therefore were not size-adjusted. Resultsindicate that there is no correlation between size-adjustedVII neuron number contrasts and group size contrasts(r � �0.168; P � 0.603; n � 12). This finding is similar tothe result obtained when phylogenetic comparative meth-ods were used to test for correlations between VII volume,VII gray level index, and social group size (Sherwood etal., 2005).
Although there was not a correlation between VII neu-ron number and social group size across primates, behav-ioral reports suggest that the facial displays and vocaliza-tions of hominids (i.e., great apes and humans) involve agreater range of facial muscle mobility compared to otherprimates (van Hooff, 1962; Andrew, 1963a, 1965; Cheva-lier-Skolnikoff, 1973; Preuschoft and van Hooff, 1995).Therefore, hominids were examined to determine whetherthese species have more facial neurons than expected fornonhominid primates of their medulla volume1/3. The re-gression line was redrawn excluding the hominid data andhominid values were compared to this prediction. Becauseof the wide dispersion of the data, the confidence intervalsof the prediction were wide and the coefficient of determi-nation was low (r2 � 0.288; P � 0.072). Thus, althoughhominids on average have 24% more facial neurons thanexpected for nonhominid primates of their medulla vol-ume1/3 and all hominid points were above the nonhominidline (y � 0.546x � 3.201), they fall within the 95% predic-tion intervals of the regression.
Taken together, these findings suggest that primatesliving in large social groups do not require significantmodifications of relative VII neuron numbers for greatervolitional control and mobility of facial expressions. In thiscontext, however, hominids display a minor departurefrom allometric expectations, which may be associatedwith increased differentiation of subsets of facial musclessurrounding the mouth. Nevertheless, across primatesthere does not appear to be a systematic relationship
between the degree of mobility of facial displays and rel-ative VII neuron number. These conclusions are sup-ported by the considerable overlap observed in the distri-bution of VII neuron numbers across anthropoid primates.
Species Differences in CytoarchitecturalOrganization
Aside from total neuron numbers, the VII may exhibitother, more subtle specializations of its cytoarchitecturalorganization that are associated with phylogenetic adap-tations of the facial muscles. Because there is a correspon-dence between subnuclei of the VII and musculotopic rep-resentation, it is possible that facial muscles that are moreelaborated or receive greater innervation density are rep-resented by a relatively larger pool of motoneurons. Incatarrhine primates, for example, the perioral muscles areparticularly well differentiated (Huber, 1931) and retro-grade tracing experiments in long-tailed macaques showthat they are innervated by proportionally more motoneu-rons than other facial muscles (Welt and Abbs, 1990).Furthermore, in Nissl-stained coronal sections of VII incatarrhines, the lateral subdivision is the largest in rela-tive size (van Buskirk, 1945; Jenny and Saper, 1987; Sa-toda et al., 1987; Welt and Abbs, 1990). One study of theVII in fetal humans, for instance, reported that motoneu-rons of the perioral muscles comprise the greatest percent-age of total nucleus volume as compared to other subnu-clei (38–46% of total VII volume) (Shindo, 1959).Interestingly, in platyrrhines, the dorsal subdivision (mo-toneurons of the upper face) is relatively enlarged so thatit is roughly equal in size to the lateral subdivision (Horta-Junior et al., 2004; see Fig. 2 in Sherwood et al., 2005).
Among other mammals, such as carnivores and chirop-terans, the pinnae are involved in specialization for soundlocalization and are capable of a high degree of mobility.Several studies have attempted to relate aspects of VIIorganization to these motor specializations of the pinnae.The medial subdivision of the VII in cats, which inner-vates the auricular muscles, has been described by severalauthors to be significantly larger relative to other subdi-visions of the nucleus (Papez, 1927; Courville, 1966a;Kume et al., 1978). A comparative retrograde HRP tracttracing study of auricular motoneurons in EgyptianRousette bats and rats revealed several apparent special-izations in the bat, which may relate to enhanced mobilityof the ears (Friauf and Herbert, 1985). In these bats, themedial subnucleus (mostly motoneurons of the pinnae)contains 49% of the total number of neurons in the VII. Incontrast, the medial subdivision in rats contains 31% ofVII neurons. Furthermore, individual pinnae muscles inbats are represented in nonoverlapping motoneuron pools,whereas in rats there is extensive overlap.
Another facial motor specialization that has been linkedto phylogenetic variation in VII organization is the explor-atory whisking of tactile vibrissae in many mammals. Inrats, nasolabial motoneurons were found to constitute thegreatest percentage of the VII (Tsai et al., 1993). In brush-tailed possums, another animal that utilizes whiskingbehavior, the greatest percentage of neurons in the VII isfound in the medial (posterior auricular) and lateral(vibrissae) subdivisions (Provis, 1977). In an effort to testthe idea that fine motor control of the whiskers in mice isaccomplished by more dense innervation of nasolabialmuscles, Ashwell (1982) compared the percentage of facialmotoneurons innervating the nasolabial region (43%) with
1073FACIAL MOTOR NUCLEUS IN MAMMALS
the percentage of total facial muscle volume made up ofthese muscles (40%). These results suggest that there maynot be a greater density of innervation to control nasola-bial muscles and, instead, variation in the size of subnu-clei corresponds to the size of the peripheral muscle fiberpopulation. Figure 6, which shows phylogenetic variationin the proportions of different VII subnuclei, suggests thatthe relative size of subnuclei is related to specializations ofperipheral muscle groups. Matching motoneuron popula-tions to peripheral targets likely occurs because a signif-icant number of the motoneurons produced during neuro-genesis are later eliminated by programmed cell death. Toa large extent, motoneuron survival during apoptosis de-pends on neurotrophic factors derived from skeletal mus-cles (Sendtner et al., 2000; Banks and Noakes, 2002).
Another morphometric variable that may correspond tofunctional specialization is neuronal size. �-motoneuronsthat supply fast-twitch muscles fibers tend to be largerthan motoneurons that supply slow-twitch fibers (Weltand Abbs, 1990). Therefore, variation in motoneuron sizeacross VII subnuclei may reflect neuromuscular special-izations of particular subsets of facial muscles. In rats, themotoneurons of the mental and posterior auricular branchof the facial nerve are significantly larger than neurons of
the zygomatico-orbital branch (Tsai et al., 1993). In ma-caques, neurons in the lateral subnucleus (perioral mus-cles) were found to have the largest mean perikarya area(Welt and Abbs, 1990).
Phylogenetic Variation in CorticofacialProjections
The presence of direct corticofacial projections originat-ing in primary motor cortex (Brodmann’s area 4) has beeninvestigated in a number of mammalian species. Olderstudies using the axon degeneration technique were un-able to reveal direct corticofacial connections in opossums(Martin, 1968; Dom et al., 1973), armadillos (Harting andMartin, 1970), phlangers (Martin et al., 1971), goats(Haarsten and Verhaart, 1967), tree shrews (Shriver andNoback, 1967), rats (Valverde, 1962; Zimmerman et al.,1964; Isokawa-Akesson and Komisaruk, 1987), and cats(Walberg, 1957; Kuypers, 1958a). More recently, antero-grade tract tracing in cats and rats have also failed tolabel direct corticofacial projections (Sokoloff and Deacon,1990; Hattox et al., 2002). In these species, projectionsfrom primary motor cortex can be traced from the pyra-midal tract to terminations in the parvocellular reticularformation adjacent to the VII. Like the basal dorsal horn
Fig. 6. Cytoarchitecture of VII in diverse mam-malian species taken from the midbody of thenucleus. A: Koala (Phascolarctos cinereus, Sub-class: Marsupiala, Order: Diprotodontia). B: Giantanteater (Myrmecophaga tridactyla, Order: Xenar-thra). C: Mustached bat (Pteronotus parnelli, Or-der: Chiroptera). D: Domestic dog (Canis lupusfamiliaris, Order: Carnivora). E: Domestic pig (Susscrofa, Order: Artiodactyla). F: Florida manatee(Trichechus manatus, Order: Sirenia). Along withthe primate, rodents, and carnivores shown in Fig-ures 2 and 3, it can be seen that the cytoarchitec-ture of the VII in mammals is highly variable. L,lateral; M, medial; D, dorsal; V, ventral. Scale bar �500 �m.
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and zona intermedia of the spinal cord, the brainstemreticular formation contains central pattern generatorsthat supply motoneurons and whose activity can be mod-ulated by descending cortical inputs. In rats, for example,lesion of the cortical motor whisker area does not abolishrhythmic whisking behavior; however, it dramatically af-fects the kinematics, coordination, and temporal patternof these movements (Gao et al., 2003).
Cortical neurons that synapse directly onto cranialnerve motoneurons have been demonstrated to exist onlyin some primate species (Walberg, 1957; Kuypers, 1958c;Kuypers and Lawrence, 1967; Morecraft et al., 2001;Jurgens and Alipour, 2002; Simonyan and Jurgens, 2003)and direct cortical projections to the VII have been re-ported only in Old World anthropoid primates. It remainsto be known whether direct cortical afferents to VII can beobserved in prosimians or New World monkeys. Neuronsin the primary motor cortex project to both the parvocel-lular reticular formation and directly to the VII in ma-caques (Kuypers, 1958c; Watson, 1973; Jenny and Saper,1987; Sokoloff and Deacon, 1990; Morecraft et al., 2001),chimpanzees (Kuypers, 1958c), and humans (Kuypers,1958b; Iwatsubo et al., 1990). In a series of classic studies,Kuypers (1958b, 1958c) used silver impregnation tech-niques for degenerating axons to reveal the projectionsfrom the ventral portion of primary motor cortex to thebrainstem in macaques, chimpanzees, and humans. Agreater number of degenerating axons was found in theVII of chimpanzees compared to macaques. In addition,compared to macaques, the lateral subnucleus (motoneu-rons of perioral muscles) of chimpanzees was moredensely innervated by cortical axons and there appearedto be a greater number of degenerating axons in the ipsi-lateral VII, especially in the lateral and dorsal subnuclei.Using the Nauta-Gygax technique to observe degenerat-ing fibers in human cerebral infarction patients, Kuypers(1958b) reported the existence of direct cortical projectionsto the VII, as well as the hypoglossal nucleus, nucleusambiguus, and trigeminal motor nucleus. These findingsin humans are generally consistent with earlier anatomi-cal studies using the Marchi technique (Weidenhammer,1896; Hoche, 1898; Barnes, 1901) as well as a more recentNauta-Gygax study (Iwatsubo et al., 1990). Transcranialmagnetic stimulation of unanesthetised human subjectsfurther supports the existence of a direct corticofacialprojection (Benecke et al., 1988).
Silver impregnation techniques for degenerating axons,however, are known to produce somewhat inconsistentresults (Heimer and RoBards, 1981). Importantly, the ex-istence of a direct corticofacial projection has been verifiedin macaques using more reliable modern anterogradetract tracing methods (Jenny and Saper, 1987; Sokoloffand Deacon, 1990; Morecraft et al., 2001; Simonyan andJurgens, 2003) and antidromic recording of primary motorcortex after activation by VII stimulation (Sirisko andSessle, 1983; Huang et al., 1988). Based on these studies,macaques appear to have only sparse direct cortical pro-jections from the primary motor cortex to the dorsal sub-nucleus (upper facial motoneurons) and strong projectionsto the lateral and ventrolateral regions of the VII (perioralmotoneurons) (Jenny and Saper, 1987; Sokoloff and Dea-con, 1990; Morecraft et al., 2001). In addition to theseprojections from primary motor cortex, other cortical mo-tor areas have been shown to innervate directly portions ofthe VII in rhesus macaques (Morecraft et al., 1996, 2001).
In particular, the greatest density of labeled axon termi-nals was found in VII deriving from primary motor cortexand ventral premotor cortex, while a lower density ofterminals originates from neurons in the supplementarymotor area, anterior cingulate, posterior cingulate, anddorsal premotor cortices (Morecraft et al., 2001). Eachcortical motor area was found to innervate preferentiallyparticular subdivisions of the VII. Most cortical motorareas, including primary motor cortex, premotor cortex,and posterior cingulate cortex, predominantly innervatethe contralateral perioral motoneurons, whereas the sup-plementary motor area and anterior cingulate bilaterallyinnervate the motoneurons of the auricular muscles andupper face muscles, respectively. A recent retrograde tran-sneuronal tracer study of the cortical innervation of orbic-ularis oculi motoneurons in rhesus macaques largely sup-ports these findings (Gong et al., 2005).
The elaboration of direct cortical innervation of lowermotoneurons in VII (as well as other cranial motor nuclei)among catarrhine primates may be a consequence of brainenlargement. With increasing brain size, the dorsal fore-brain disproportionately enlarges compared to the spinalcord and brainstem (Finlay and Darlington, 1995), leadingto the development of more widespread cortical projec-tions to subcortical targets via activity-dependent axonsorting processes (Deacon, 1997; Striedter, 2005). A corre-lation between increased brain size and direct corticomo-toneuronal connections is also seen in the spinal cord,where cortical axons project to progressively more caudalparts of the cord and penetrate further into the ventralhorn to reach motoneurons with increasing brain size inmammals (Striedter, 2005).
Direct corticomotoneuronal connections might enhancethe diversity and flexibility of motor behaviors. Increasedcorticospinal projections are correlated with some mea-sures of manual dexterity in mammals (Heffner and Mas-terton, 1975, 1983; Iwaniuk et al., 1999) and the ability tolearn diverse vocalizations in birds is associated with thepresence of direct connections between the telencephalonand brainstem vocal motoneurons (Striedter, 1994). Nota-bly, vocal learning abilities have recently been reportedfor elephants and dolphins (Janik, 2000; Poole et al.,2005). These mammals have relatively enlarged neocorti-ces, suggesting that they might also have direct corticalinnervation of orofacial motoneurons. Current method-ological limitations, however, make this prediction diffi-cult to test.
Among catarrhine primates, behavioral observationssupport the idea that greater direct corticofacial connec-tions subserve enhanced volitional control of facial move-ments. Great apes, but not monkeys, have been frequentlyobserved to make nonemotional facial expressions seem-ingly for the purpose of play and self-amusement (vanLawick-Goodall, 1968; Chevalier-Skolnikoff, 1976, 1982).Additionally, although several species of anthropoids ap-pear to have the capacity to inhibit voluntarily emotionalvocalizations and facial expressions to deceive social part-ners (de Waal, 1982, 1986; Goodall, 1986; Byrne andWhiten, 1992), great apes and humans may be moreskilled at suppressing affective output for the purposes oftactical deception (Yerkes and Yerkes, 1929; Chevalier-Skolnikoff, 1976, 1982; Whiten and Byrne, 1988; Byrneand Whiten, 1992). Finally, the coordination of orofacialand laryngeal muscles in human speech probably requires
1075FACIAL MOTOR NUCLEUS IN MAMMALS
the existence of descending cortical control of motoneu-rons (Deacon, 1997).
CONCLUSIONConsidering the involvement of superficial facial mus-
cles in diverse behaviors ranging from blinking to thenegotiation of social networks, the anatomic organizationof the VII within any given species reflects the combina-tion of evolutionarily conservative organizational pro-grams as well as lineage-specific specializations. The gen-eral musculotopic plan of the VII is consistent across allmammals, suggesting a link to early target-derived axonguidance cues. Nonetheless, interspecific variation in therelative distribution of motoneurons for different subsetsof facial muscles demonstrates that specialization of theperiphery has an influence on the cytoarchitectural orga-nization of VII.
Although studies of the brainstem and midbrain affer-ent connectivity of VII have not employed explicit compar-isons among species, these circuits regulate involuntaryactivity of the facial muscles, such as protective reflexesand orienting movements, and are likely to be similaracross species. In contrast, the development of direct neo-cortical projections to the VII represents an importantanatomical substrate for the evolution of voluntary controlof the muscles of facial expression in Old World anthro-poid primates and may underlie complex facial behaviorsin other lineages.
Erwin, P.J. Gannon, and S.C. McFarlin for discussionsthat helped to formulate many of the ideas presented inthis manuscript. Brain materials used in these studieswere generously provided by the Comparative Neurobiol-ogy of Aging Resource, Cleveland Metroparks Zoo, theNeuroanatomical Collection of the National Museum ofHealth and Medicine, Drs. P.R. Hof, J.J. Wenstrup, K.Zilles, H.D. Frahm, K. Semendeferi, and M. Henneberg.Graphic design support was provided by E. Ando-Yeapand B. von Derau. Supported by the National ScienceFoundation (DBI-9602234 to NYCEP).
NOTE ADDED IN PROOFAs this manuscript was going to press, an article was
published that reported the presence of monosynaptic con-nections from neurons in vibrissae motor cortex to facialmotoneurons in rats (Grinevich et al., 2005). Using a len-tivirus-based anterograde axon tracing methodology, thisstudy revealed synaptic contacts of labeled axons ontolateral subnucleus facial motoneurons by electron micros-copy. These findings suggest that direct cortico-motoneu-ron connections may be essential to the generation ofcomplex whisker movements of rats during tactile explo-ration. Most importantly, these results challenge the ideathat direct corticofacial pathways are found exclusively inanthropoid primates.
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