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Home , Cranial nerves, Facial motor nucleus, Facial nerve, Human brain, Hypoglossal nucleus, Nucleus ambiguus

THE ANATOMICAL RECORD PART A 287A:1067–1079 (2005)

Comparative of the Facial Motor in , With an Analysis of Numbers in

CHET C. SHERWOOD* Department of Anthropology and School of Biomedical Sciences, Kent State University, Kent, Ohio

ABSTRACT The (VII) contains motoneurons that innervate the of expression. In this review, the comparative anatomy of this nucleus is examined. Several aspects of the anatomical organization of the VII appear to be common across mammals, such as the distribution of neuron types, general topography of muscle representation, and afferent con- nections from the and brainstem. Phylogenetic specializations are apparent in the proportion of allocated to the representation of subsets of muscles and the degree of differentiation among subnuclei. These interspe- cific differences may be related to the elaboration of certain facial muscles in the context of socioecological adaptations such as whisking behavior, sound localization, vocalization, and facial expression. Furthermore, current evidence indicates that direct descending corticomotoneuron projections in the VII are present only in catarrhine primates, suggesting that this connectivity is an important substrate for the evolution of enhanced mobility and flexibility in facial expression. Data are also presented from a stereologic analysis of VII neuron numbers in 18 species and a scandentian. Using phylogenetic comparative statistics, it is shown that there is not a correlation between group size and VII neuron number (adjusted for medulla volume) among primates. Great apes and , however, display moderately more VII neurons that expected for their medulla size. © 2005 Wiley-Liss, Inc.

Key words: facial motor nucleus; comparative ; facial expression; mammals; primates; stereology; motoneuron

Therian mammals are characterized by well-differenti- these basic mammalian adaptations within particular lin- ated superficial facial muscles (also known as muscles of eages, subsets of facial muscles have increased in com- facial expression) derived from the second branchial arch. Compared to nonmammalian whose facial muscle actions are limited to opening and closing the apertures encircling the mouth, eyes, and nostrils, mam- Grant sponsor: the National Science Foundation; Grant num- mals are capable of a much more varied range of facial ber: BCS-0121286; Grant sponsor: the Leakey Foundation; Grant movements (van Hooff, 1967). Greater mobility of the sponsor: the Wenner-Gren Foundation for Anthropological Re- and cheeks may have evolved in stem mammals to facili- search; Grant sponsor: Mount Sinai School of ; Grant sponsor: Kent State University. tate neonatal suckling and more extensive chewing of food *Correspondence to: Chet C. Sherwood, Department of Anthro- (Huber, 1930). Additionally, with the evolution of in- pology, Kent State University, 226 Lowry Hall, Box 5190, Kent, creased energetic demands related to homeothermy in OH 44242. Fax: 330-672-2999. E-mail: [email protected] mammals, facial muscles may have become differentiated Received 16 August 2005; Accepted 17 August 2005 to facilitate mobility of the external and whisking DOI 10.1002/ar.a.20259 movements of tactile vibrissae to explore more actively the Published online 2 October 2005 in Wiley InterScience environment for food items (van Hooff, 1967). Building on (www.interscience.wiley.com).

© 2005 WILEY-LISS, INC. 1068 SHERWOOD

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 ϭ 100 ␮m.

plexity and expanded concomitantly with socioecological phorylated neurofilament protein (Tsang et al., 2000), and adaptations. For example, the mass of musculature sur- calcineurin (Strack et al., 1996). Morphological and tract rounding the blowhole in odontocete cetaceans alters the tracing studies in rats and cats suggest that the VII con- shape of the spermaceti during the emission of tains few, if any, (Courville, 1966a; McCall biosonar (Cranford et al., 1996). In anthropoid primates, a and Aghajanian, 1979). Injection of horseradish peroxi- number of tractor muscles (e.g., zygomaticus major, zygo- dase (HRP) into the main trunk of the facial , for maticus minor, levator labii superioris, depressor anguli instance, results in retrograde labeling of 98% of neurons oris, depressor labii inferioris, and ) surround the in the VII, indicating the virtual absence of neurons that mouth to configure the shape of the lips for vocalizations do not directly innervate facial muscles (McCall and Agha- and facial displays (Huber, 1931). Perhaps the most im- janian, 1979). In addition, size histograms of facial neu- pressive example of facial musculature specialization is rons in macaque monkeys (Welt and Abbs, 1990) and rats the elongated and highly mobile trunk of , which (Martin et al., 1977) show a unimodal distribution, indi- is composed of several layers of differentially oriented cating that few small ␥-motoneurons are found in the VII. muscle bundles derived exclusively from the caninus mus- This concords with reports that muscle spindles, which cle (also known as levator anguli oris) (Endo et al., 2001). are innervated by ␥-motoneurons, occur in very low abun- Neurons within the facial motor nucleus (VII) of the dance in superficial facial muscles (Bowden and Mahran, brainstem innervate the superficial facial musculature 1956; Olkowski and Manocha, 1973; Dubner et al., 1978; and hence comprise the final common output for circuits Brodal, 1981; Sufit et al., 1984). related to various behaviors, including emotional expres- As with other motor nuclei (e.g., hypoglossal) (Sokoloff sion, vocal communication, , ingestion, protec- and Deacon, 1992), the neurons of the VII are arranged in tive reflexes, and sensory exploration of the environment. subnuclei that lie adjacent to one another in longitudinal In addition to the main VII, the accessory facial nucleus columns. Because each subnucleus extends rostrocau- (also called the suprafacial nucleus or the dorsal facial dally for a different distance, the differentiation of subnu- nucleus) contains motoneurons of deep facial muscles (i.e., clei is most apparent in coronal sections at the middle stylohyoid and the posterior belly of the digastric). third of the VII. Historically, the number of VII subnuclei of motoneurons in the main VII and the accessory facial recognized by researchers has varied considerably de- nucleus exit the brainstem together on the ipsilateral side pending on species, anatomical methods, and subjective as the (CN VII), then leave the base of the assessment. For example, based on Nissl staining pat- via the stylomastoid and enter the parotid terns, Welt and Abbs (1990) described six subnuclei in gland, where the main trunk of the facial nerve divides long-tailed macaques (Macaca fascicularis), Jenny and into several major branches. Saper (1987) described four subnuclei in M. fasciularis, Considering the central involvement of the VII in di- and Satoda et al. (1987) described five subnuclei in Japa- verse sensorimotor adaptations of the facial muscles nese macaques (M. fuscata). Some discrepancy may arise across phylogeny, the comparative neurobiology of the VII from the fact that facial neurons are arranged in irregular is of special interest. This article presents an overview of clusters and cytoarchitectural boundaries between subnu- phylogenetic variation in the neuroanatomical structure clei are not well defined in most species (Papez, 1927; and connectivity of the VII in mammals. Vraa-Jensen, 1942; van Buskirk, 1945; Courville, 1966a; Dom et al., 1973; Martin and Lodge, 1977; Porter et al., SIMILARITIES ACROSS PHYLOGENY 1989; Welt and Abbs, 1990; Yew et al., 1996; Sherwood et al., 2005). Nonetheless, some boundaries among subnuclei General Cytoarchitectural Plan can be more clearly delimited in stained for The VII is composed predominantly of multipolar ␣-mo- and nonphosphorylated neurofilament protein (Fig. 2). In toneurons (Fig. 1), which express the biochemical markers these preparations, however, there is not clear differenti- choline acetyltransferase (Ichikawa and Hirata, 1990; ation between all the subnuclei identifiable based on cy- Ichikawa and Shimizu, 1998; Tsang et al., 2000), nonphos- toarchitecture, suggesting that there may be fewer func- FACIAL MOTOR NUCLEUS IN MAMMALS 1069 Conserved Musculotopy The topographic representation of the muscles of facial expression in the VII has been studied in several species. Unfortunately, interpretation of older studies is hampered by the fact that retrograde cellular pathologic changes are somewhat unpredictable (Martin and Lodge, 1977). In addition, many retrograde cell degeneration studies involved sectioning of a single peripheral nerve branch. Individual facial nerve branches, however, may innervate a number of different muscles and a particular muscle 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 nerve may have been influenced by methodological artifact (van Gehuchten, 1898; Marinesco, 1899; Yagita, 1910; Papez, 1927; Hogg, 1928; Nishi, 1965; Courville, 1966a), not the true anatomical organization of the nucleus. More recent studies utilizing sensitive retrograde tract tracers such as HRP and fluorescence dyes have provided more detailed and reliable data on the musculotopic orga- nization of facial motoneurons in several species, includ- ing brush-tailed possums (Provis, 1977), opossums (Dom and Zielinski, 1977; Dom, 1982), pigs (Marshall et al., 2005), guinea pigs (Hamner et al., 1989), rats (Watson et al., 1982; Hinrichsen and Watson, 1984; Klein and Rhoades, 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 and Abbs, 1990; VanderWerf et al., 1997, 1998; Morecraft et al., 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 a basic pattern of muscle representation exists in the VII that is common to all mammals (Dom, 1982; Komiyama et al., 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 is represented along the dorsoventral axis of the nucleus. Thus, muscles surrounding the mouth are represented in lateral regions of the VII, posterior auricular and muscles are rep- resented in medial regions, and neurons that are located intermediate innervate muscles around the eyes, the fore- head, and anterior auricular muscles (Fig. 4). Discrete Fig. 2. Coronal sections through the midbody of the VII in a long- tailed macaque monkey (Macaca fascicularis) showing architecture as injections of retrograde tracers into facial muscles of ma- revealed by staining for (A) Nissl substance, (B) myelin, and (C) non- caques and capuchins (Welt and Abbs, 1990; Horta-Junior phosphorylated neurofilament protein (NPNFP). Scale bar ϭ 250 ␮m. et al., 2004) and individual whisker follicle muscles of rats (Klein and Rhoades, 1985) indicate that different regions of the same facial muscle are represented at all rostrocau- dal levels within the nucleus. tionally and anatomically distinct subdivisions than Strong evidence for evolutionary conservation of this usually recognized. Also, it is interesting that VII subnu- musculotopic plan in the mammalian VII comes from trac- clei in larger-brained species tend to be more completely ing experiments in the marsupial North American opos- separated by interstitial space as compared to their small- sum (Didelphis virginiana), which show that despite poor er-brained relatives (Fig. 3). This suggests that there is differentiation among subnuclei, the basic mammalian relative elaboration of the dendritic arbors of these mo- plan of musculotopic representation is present (Dom, toneurons as a consequence of scaling rules (Sherwood et 1982). Data from mutant strains such as reeler mice (Ter- al., 2005). These allometric trends may contribute to the ashima et al., 1993) and Shaking Rat Kawasaki (Setsu et appearance of more distinct VII subnuclei in some species; al., 2001), furthermore, indicate that the musculotopic however, the functional significance of such differentia- organization of VII is preserved in spite of abnormal mi- tion is not known. gration of facial and atypical VII cytoarchitec- 1070 SHERWOOD

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 weight, versus (B) capybara (Hydrochaeris hydrochaeris), approximately 55 g brain 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 species with larger . Scale bar ϭ 250 ␮m.

tain amount of overlap may exist among motoneuron pools for different muscles in the VII. For example, overlapping motoneuron pools have been described for different peri- oral muscles in pigs (Marshall et al., 2005), orbicularis oculi and the frontalis of rats (Watson et al., 1982), the anterior and posterior auricular levators of bats (Friauf and Herbert, 1985), upper and lower eyelids in cats (Shaw and Baker, 1985), and and orbicularis oris in macaques (Welt and Abbs, 1990). This contrasts with the more orderly somatotopic representation of mechanore- ceptors in the principal trigeminal sensory nucleus (Bel- ford and Killackey, 1979). However, the apparent inter- Fig. 4. Schematic diagram showing the position of muscle represen- mingling of muscle representation may, to some extent, be tation relative to the VII that can be generalized across mammals. due to the experimental artifact of tracer spread to adja- Although there is some consistency in the nomenclature for subnuclei across studies of the same species, given interspecific variation in the cent muscles. Populin and Yin (1995) have demonstrated anatomical orientation of the nucleus as a whole, as well as the degree extremely specific topography of pinna muscle represen- to which subnuclei are differentiated, existing subnucleus classification tation in the mediodorsal subnucleus of the cat VII by cannot be easily applied to all mammals. using very small injections (1–2 ␮l) of cholera toxin B-HRP into individual pinna muscles. Discrete motoneuron pools have also been shown to innervate different portions of the ture. While it is known that ephrins and hepatocyte in rhesus macaques (VanderWerf growth factor are important guidance cues that di- et al., 1998). rect developing motor axons to enter the mesenchyme of Afferent Connections From Brainstem and the appropriate branchial arch (Caton et al., 2000; Ku¨ryet al., 2000), the molecules that direct growth cones toward Midbrain specific target muscles in the periphery are not yet known Studies, mostly in rodents, have shown that the VII (Chandrasekhar, 2004). Based on the similarities in VII receives afferent inputs from diverse brainstem and mid- musculotopy across diverse species, however, it would brain sites, reflecting its role in various complex orofacial seem that the molecular cues that guide axons to target behaviors. In addition, pharmacological and anatomical muscles in the second branchial arch are evolutionarily data indicate that the responsiveness of facial motoneu- conserved. rons is regulated by several neuromodulatory systems, While the fundamental topographic organization of including (Takeuchi et al., 1983; Li et al., 1993b; muscle representation in the VII seems to be similar Tallaksen-Greene et al., 1993; Leger et al., 2001; Hattox et across mammals, the precise mapping between peripheral al., 2003), substance P (Senba and Tohyama, 1985; Tal- innervation territories and anatomical subdivisions of the laksen-Greene et al., 1993; Yew et al., 1996), nucleus have not been fully elucidated within any species, (Fort et al., 1989; Yew et al., 1996), and (Fort let alone across species. It appears, however, that a cer- et al., 1989; Ichikawa and Hirata, 1990; Yew et al., 1996; FACIAL MOTOR NUCLEUS IN MAMMALS 1071 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) Mus musculus 2 2,027 — (Ashwell, 1982) 5 6,060 5,350–6,600 (Nimchinsky et al., 2000) Canis familiaris 20 8,613 6,800–11,510 (van Buskirk, 1945) 4 15,800 — (Blinkov and Ponomarev, 1965) 4 — 12,330–19,060 (Blinkov and Glezer, 1968) Felis silvestris 15 — 9,100–10,376 (Maleci, 1934) 26 7,734 4,610–9,790 (van Buskirk, 1945) Rousettus aegyptiacus 2 4,126 — (Friauf and Herbert, 1985) Trichosurus vulpecula 6 5,342 — (Provis, 1977)

Ichikawa and Shimizu, 1998; Kus et al., 2003). For exam- et al., 1988; Hattox et al., 2002; Dauvergne et al., 2004). ple, the presence of very high densities of 5-HT2 receptors Inputs from the , which relay cerebellar infor- in the VII suggests that serotonergic facilitation of facial mation to facial motoneurons (Holstege et al., 1984; Hol- motoneuron excitability is important in the regulation of stege and Tan, 1988), may play a role in the fine adjust- central pattern motor generating networks for blink re- ment of nasolabial activity during whisking behaviors flexes, respiration, rhythmic whisking, and mastication (Hinrichsen and Watson, 1983). Orientation of the ears to (McCall and Aghajanian, 1979; Pazos et al., 1985; Mengod objects of interest detected in the visual field may be et al., 1990; Rasmussen and Aghajanian, 1990; LeDoux et mediated by inputs to motoneurons of al., 1998). the pinnae (Dom et al., 1973; Harting et al., 1973; Kilimov Afferent inputs to the VII have been identified originat- and Milev, 1973). Additionally, the presence of inputs ing in the brainstem, including locations throughout the from the superior colliculus to palpebrae motoneurons , the , hypoglossal suggests a substrate for saccade-related lid movements nucleus, sensory trigeminal complex, paralemniscal nu- (Vidal et al., 1988; Dauvergne et al., 2004). Collectively, cleus, and parabrachial nucleus (Hinrichsen and Watson, these data illustrate that VII motoneurons integrate an 1983; Fay and Norgren, 1997; Pinganaud et al., 1999; array of inputs to subserve adaptive behaviors of the oro- Dauvergne et al., 2001; Popratiloff et al., 2001). The med- facial muscles. ullary reticular formation is the greatest source of affer- ents to all orofacial cranial nerve motor nuclei, including PHYLOGENETIC SPECIALIZATIONS VII (Travers and Norgren, 1983). Tracing studies have Counts of Facial Neuron Numbers Across identified several groups of inhibitory GABA and glycin- Species ergic premotor neurons in this region, as well as the paralemniscal zone, which project to the VII, trigeminal Several studies have reported total neuron number for motor, ambiguus, and hypoglossal nuclei to coordinate the VII in different species (Table 1). It is difficult, how- mastication and (Travers and Norgren, 1983; ever, to compare neuron numbers among species based on Li et al., 1997). Some individual neurons in the reticular these data because many older studies used assumption- formation have been shown to possess collateral axons based counting methods. Typically, these studies were that within several different cranial orofacial mo- performed by counting the two-dimensional projected pro- tor nuclei (Amri et al., 1990; Li et al., 1993a; Popratiloff et files of neurons from relatively thin histological sections. al., 2001). It is that projections from the sensory Because large cells have a greater chance of being sam- trigeminal complex, particularly the magnocellular por- pled within such sections, the number of profiles counted tion of the subnucleus caudalis, provide sensory feedback does not have a simple or known relationship to the total to facial motoneurons involved in whisking movements of number of cells in a given volume (Thune and Pakken- the vibrissae (Erzurumlu and Killackey, 1979). berg, 2000). Corrections for these biases, such as the Aber- The VII also receives projections from the midbrain, crombie correction, make assumptions about the shape including the superior colliculus, red nucleus, periaque- and orientation of cells that are rarely met by actual ductal gray, and several nuclei involved in oculomotor biological objects (Mouton, 2002). As a consequence, inter- control (Courville, 1966b; Martin and Dom, 1970; Mizuno group differences in the size, shape, and orientation of et al., 1971; Edwards, 1972; Yu et al., 1972; Panneton and cells can lead to significant bias in results based on these Martin, 1979, 1983; Hinrichsen and Watson, 1983; Vidal methods. 1072 SHERWOOD TABLE 2. Total number of VII neurons estimated by the optical fractionator Mean CE Species N Mean CV of estimate Tupaia glis 2 3,482 0.06 0.09 Loris tardigradus 2 4,257 0.06 0.07 Galago senegalensis 1 3,517 — 0.06 Nycticebus coucang 1 5,302 — 0.05 Saguinus mystax 1 6,075 — 0.04 Saimiri sciureus 5 7,847 0.31 0.06 Aotus trivirgatus 5 9,120 0.28 0.09 Lagothrix lagothricha 1 5,680 — 0.12 Alouatta seniculus 1 4,022 — 0.07 Macaca fascicularis 6 6,060 0.14 0.06 Macaca mulatta 2 4,857 0.13 0.07 Erythrocebus patas 6 9,721 0.24 0.07 Papio cynocephalus 1 10,898 — 0.05 Papio anubis 1 7,655 — 0.05 Hylobates lar 1 5,619 — 0.15 Pongo pygmaeus 4 9,963 0.15 0.06 Gorilla gorilla 4 10,604 0.15 0.06 Pan troglodytes 5 11,169 0.30 0.06 Homo sapiens 4 10,470 0.14 0.06

Another limitation of existing data on VII neuron num- ber is that only a few distantly related species have been studied. Such phylogenetically dispersed data pose com- plications in establishing the relationship between facial neuron number and the evolution of fine of facial movements. Previous comparative studies, for in- stance, found that dogs and cats have more facial neurons than primates (van Buskirk, 1945; Blinkov and Pono- marev, 1965). These findings led Blinkov and Ponomarev (1965: p. 299) to conclude that “considerable complications of functions is by no means connected with any increase in the number of neurons in the corresponding motor nuclei of the brain stem.” However, carnivores and primates are separated by approximately 79–88 million years of inde- pendent evolution (Murphy et al., 2001). The functional Fig. 5. A: The results of optical fractionator estimates of total neuron significance of differences in neuron numbers becomes number in VII. B: The double-logarithmic least-squares (LS) regression of obscured in comparisons of such vastly divergent lineages. VII neuron number on medulla volume1/3 is shown. The LS line is fit to all It is difficult to discern based on these data whether dif- data and the great ape and points are depicted as closed circles ferences in neuron numbers among mammalian lineages for comparison. Values for species mean medulla volume were obtained are adaptive specializations or have been driven to fixa- from Sherwood et al. (2005). Because Shapiro Wilk’s W-tests showed that variables were not normally distributed, regression analyses used tion by neutral drift or pleiotropy. logarithmic (base 10) transformed data. The cube root of medulla volume was used to adjust volumetric measures to the same dimensionality as Stereologic Analysis of Facial Neuron Number neuron number. in Primates To address some of these limitations, Sherwood (2003) performed designed-based stereologic analysis of VII neu- amount of intraspecific variation, there was extensive ron numbers within a restricted phylogenetic sample in- overlap in VII neuron number among individuals of dif- cluding 18 species of primates and 1 scandentian (Tupaia ferent taxa (Fig. 5A). Notably, values for many monkeys glis). The total number of neurons in the left-side VII was fell within the range of great apes and humans. estimated based on Nissl-stained sections using the opti- Figure 5B shows the allometric relationship between cal fractionator method (West et al., 1991). species mean VII neuron number and medulla volume1/3 Table 2 shows species mean, coefficient of variation in this sample. Overall, the relationship between these (CV), and coefficient of error (CE) of VII neuron number variables is only moderately strong (r2 ϭ 0.566; P ϭ 0.001; estimates. Among primates, species mean VII neuron n ϭ 16) and many species deviate substantially from ex- number varied by a factor of 3.2. This relatively minimal pectations based on the regression function. Of particular range of variation contrasts with the much wider range interest is that the greatest departure from predicted VII over which VII volume (23.6-fold) and medulla volume neuron numbers is Aotus trivirgatus, which have 42% (44.3-fold) vary across the same species (Sherwood et al., more VII neurons than predicted for a primate of their 2005). Due to this narrow range and the considerable medulla size (studentized deleted residual ϭ 2.33). It is FACIAL MOTOR NUCLEUS IN MAMMALS 1073 noteworthy that owl monkeys are active in a nocturnal between the degree of mobility of facial displays and rel- environment and consequently do not rely extensively on ative VII neuron number. These conclusions are sup- the visual channel for social communication (Moyniham, ported by the considerable overlap observed in the distri- 1967). In this regard, they have among the most poorly bution of VII neuron numbers across anthropoid primates. differentiated facial muscles of any anthropoid (Huber, Species Differences in Cytoarchitectural 1931) and they use very few facial expressions in their social communication (Moyniham, 1967). This suggests Organization that variation in VII neuron numbers may not be strictly Aside from total neuron numbers, the VII may exhibit associated with facial muscle mobility. other, more subtle specializations of its cytoarchitectural To investigate further a possible relationship with spe- organization that are associated with phylogenetic adap- cializations for facial expression, VII neuron numbers tations of the facial muscles. Because there is a correspon- were examined for a correlation with social group size to dence between subnuclei of the VII and musculotopic rep- test the hypothesis that relatively greater facial muscle resentation, it is possible that facial muscles that are more innervation is necessary in species that live in large gre- elaborated or receive greater innervation density are rep- garious groups that rely on facial displays to mediate their resented by a relatively larger pool of motoneurons. In social interactions (Andrew, 1963b). Data on social group catarrhine primates, for example, the perioral muscles are size obtained from Barton (1999) were used as an index of particularly well differentiated (Huber, 1931) and retro- social (Dunbar, 1992, 1998). To control for grade tracing experiments in long-tailed macaques show phylogenetic bias in the data set, independent contrasts that they are innervated by proportionally more motoneu- (Felsenstein, 1985; Garland et al., 1999) were calculated rons than other facial muscles (Welt and Abbs, 1990). from log-transformed species mean data based on the to- Furthermore, in Nissl-stained coronal sections of VII in pology and untransformed branch lengths from a compos- catarrhines, the lateral subdivision is the largest in rela- ite phylogeny of primates (Purvis, 1995). Because con- tive size (van Buskirk, 1945; Jenny and Saper, 1987; Sa- trasts in VII neuron number were significantly correlated toda et al., 1987; Welt and Abbs, 1990). One study of the with contrasts in medulla volume1/3, VII neuron number VII in fetal humans, for instance, reported that motoneu- contrasts were adjusted by calculating residuals from the rons of the perioral muscles comprise the greatest percent- least-squares regression line on medulla volume1/3. Group age of total nucleus volume as compared to other subnu- size contrasts were not correlated with medulla volume1/3 clei (38–46% of total VII volume) (Shindo, 1959). contrasts and therefore were not size-adjusted. Results Interestingly, in platyrrhines, the dorsal subdivision (mo- indicate that there is no correlation between size-adjusted toneurons of the upper face) is relatively enlarged so that VII neuron number contrasts and group size contrasts it is roughly equal in size to the lateral subdivision (Horta- (r ϭϪ0.168; P ϭ 0.603; n ϭ 12). This finding is similar to Junior et al., 2004; see Fig. 2 in Sherwood et al., 2005). the result obtained when phylogenetic comparative meth- Among other mammals, such as carnivores and chirop- ods were used to test for correlations between VII volume, terans, the pinnae are involved in specialization for sound VII gray level index, and social group size (Sherwood et localization and are capable of a high degree of mobility. al., 2005). Several studies have attempted to relate aspects of VII Although there was not a correlation between VII neu- organization to these motor specializations of the pinnae. ron number and social group size across primates, behav- The medial subdivision of the VII in cats, which inner- ioral reports suggest that the facial displays and vocaliza- vates the auricular muscles, has been described by several tions of hominids (i.e., great apes and humans) involve a authors to be significantly larger relative to other subdi- greater range of facial muscle mobility compared to other visions of the nucleus (Papez, 1927; Courville, 1966a; primates (van Hooff, 1962; Andrew, 1963a, 1965; Cheva- Kume et al., 1978). A comparative retrograde HRP tract lier-Skolnikoff, 1973; Preuschoft and van Hooff, 1995). tracing study of auricular motoneurons in Egyptian Therefore, hominids were examined to determine whether Rousette bats and rats revealed several apparent special- these species have more facial neurons than expected for izations in the bat, which may relate to enhanced mobility nonhominid primates of their medulla volume1/3. The re- of the ears (Friauf and Herbert, 1985). In these bats, the gression line was redrawn excluding the hominid data and medial subnucleus (mostly motoneurons of the pinnae) hominid values were compared to this prediction. Because contains 49% of the total number of neurons in the VII. In of the wide dispersion of the data, the confidence intervals contrast, the medial subdivision in rats contains 31% of of the prediction were wide and the coefficient of determi- VII neurons. Furthermore, individual pinnae muscles in nation was low (r2 ϭ 0.288; P ϭ 0.072). Thus, although bats are represented in nonoverlapping motoneuron pools, hominids on average have 24% more facial neurons than whereas in rats there is extensive overlap. expected for nonhominid primates of their medulla vol- Another facial motor specialization that has been linked ume1/3 and all hominid points were above the nonhominid to phylogenetic variation in VII organization is the explor- line (y ϭ 0.546x ϩ 3.201), they fall within the 95% predic- atory whisking of tactile vibrissae in many mammals. In tion intervals of the regression. rats, nasolabial motoneurons were found to constitute the Taken together, these findings suggest that primates greatest percentage of the VII (Tsai et al., 1993). In brush- living in large social groups do not require significant tailed possums, another animal that utilizes whisking modifications of relative VII neuron numbers for greater behavior, the greatest percentage of neurons in the VII is volitional control and mobility of facial expressions. In this found in the medial (posterior auricular) and lateral context, however, hominids display a minor departure (vibrissae) subdivisions (Provis, 1977). In an effort to test from allometric expectations, which may be associated the idea that fine motor control of the whiskers in mice is with increased differentiation of subsets of facial muscles accomplished by more dense innervation of nasolabial surrounding the mouth. Nevertheless, across primates muscles, Ashwell (1982) compared the percentage of facial there does not appear to be a systematic relationship motoneurons innervating the nasolabial region (43%) with 1074 SHERWOOD

Fig. 6. Cytoarchitecture of VII in diverse mam- malian species taken from the midbody of the nucleus. A: Koala (Phascolarctos cinereus, Sub- class: Marsupiala, Order: Diprotodontia). B: Giant anteater (Myrmecophaga tridactyla, Order: Xenar- thra). C: Mustached bat (Pteronotus parnelli, Or- der: Chiroptera). D: Domestic dog (Canis lupus familiaris, Order: Carnivora). E: Domestic pig (Sus scrofa, Order: Artiodactyla). F: Florida manatee (Trichechus manatus, Order: Sirenia). Along with the 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 ϭ 500 ␮m.

the percentage of total facial muscle volume made up of the zygomatico-orbital branch (Tsai et al., 1993). In ma- these muscles (40%). These results suggest that there may caques, neurons in the lateral subnucleus (perioral mus- not be a greater density of innervation to control nasola- cles) were found to have the largest mean perikarya area bial muscles and, instead, variation in the size of subnu- (Welt and Abbs, 1990). clei corresponds to the size of the peripheral muscle fiber Phylogenetic Variation in Corticofacial population. Figure 6, which shows phylogenetic variation in the proportions of different VII subnuclei, suggests that Projections the relative size of subnuclei is related to specializations of The presence of direct corticofacial projections originat- peripheral muscle groups. Matching motoneuron popula- ing in primary motor (Brodmann’s area 4) has been tions to peripheral targets likely occurs because a signif- investigated in a number of mammalian species. Older icant number of the motoneurons produced during neuro- studies using the axon degeneration technique were un- genesis are later eliminated by programmed cell . To able to reveal direct corticofacial connections in opossums a large extent, motoneuron survival during apoptosis de- (Martin, 1968; Dom et al., 1973), armadillos (Harting and pends on neurotrophic factors derived from skeletal mus- Martin, 1970), phlangers (Martin et al., 1971), goats cles (Sendtner et al., 2000; Banks and Noakes, 2002). (Haarsten and Verhaart, 1967), tree shrews (Shriver and Another morphometric variable that may correspond to Noback, 1967), rats (Valverde, 1962; Zimmerman et al., functional specialization is neuronal size. ␣-motoneurons 1964; Isokawa-Akesson and Komisaruk, 1987), and cats that supply fast-twitch muscles fibers tend to be larger (Walberg, 1957; Kuypers, 1958a). More recently, antero- than motoneurons that supply slow-twitch fibers (Welt grade tract tracing in cats and rats have also failed to and Abbs, 1990). Therefore, variation in motoneuron size label direct corticofacial projections (Sokoloff and Deacon, across VII subnuclei may reflect neuromuscular special- 1990; Hattox et al., 2002). In these species, projections izations of particular subsets of facial muscles. In rats, the from primary can be traced from the pyra- motoneurons of the mental and posterior auricular branch midal tract to terminations in the parvocellular reticular of the facial nerve are significantly larger than neurons of formation adjacent to the VII. Like the basal dorsal horn FACIAL MOTOR NUCLEUS IN MAMMALS 1075 and zona intermedia of the , the brainstem In particular, the greatest density of labeled axon termi- reticular formation contains central pattern generators nals was found in VII deriving from that supply motoneurons and whose activity can be mod- and ventral , while a lower density of ulated by descending cortical inputs. In rats, for example, terminals originates from neurons in the supplementary lesion of the cortical motor whisker area does not abolish motor area, anterior cingulate, posterior cingulate, and rhythmic whisking behavior; however, it dramatically af- dorsal premotor cortices (Morecraft et al., 2001). Each fects the kinematics, coordination, and temporal pattern cortical motor area was found to innervate preferentially of these movements (Gao et al., 2003). particular subdivisions of the VII. Most cortical motor Cortical neurons that synapse directly onto cranial areas, including primary motor cortex, premotor cortex, nerve motoneurons have been demonstrated to exist only and posterior , predominantly innervate in some primate species (Walberg, 1957; Kuypers, 1958c; the contralateral perioral motoneurons, whereas the sup- Kuypers and Lawrence, 1967; Morecraft et al., 2001; plementary motor area and anterior cingulate bilaterally Ju¨ rgens and Alipour, 2002; Simonyan and Ju¨ rgens, 2003) innervate the motoneurons of the auricular muscles and and direct cortical projections to the VII have been re- upper face muscles, respectively. A recent retrograde tran- ported only in Old World anthropoid primates. It remains sneuronal tracer study of the cortical innervation of orbic- to be known whether direct cortical afferents to VII can be ularis oculi motoneurons in rhesus macaques largely sup- observed in prosimians or New World monkeys. Neurons ports these findings (Gong et al., 2005). in the primary motor cortex project to both the parvocel- The elaboration of direct cortical innervation of lower lular reticular formation and directly to the VII in ma- motoneurons in VII (as well as other cranial motor nuclei) caques (Kuypers, 1958c; Watson, 1973; Jenny and Saper, among catarrhine primates may be a consequence of brain 1987; Sokoloff and Deacon, 1990; Morecraft et al., 2001), enlargement. With increasing , the dorsal fore- (Kuypers, 1958c), and humans (Kuypers, brain disproportionately enlarges compared to the spinal 1958b; Iwatsubo et al., 1990). In a series of classic studies, cord and brainstem (Finlay and Darlington, 1995), leading Kuypers (1958b, 1958c) used silver impregnation tech- to the development of more widespread cortical projec- niques for degenerating axons to reveal the projections tions to subcortical targets via activity-dependent axon from the ventral portion of primary motor cortex to the sorting processes (Deacon, 1997; Striedter, 2005). A corre- brainstem in macaques, chimpanzees, and humans. A lation between increased brain size and direct corticomo- greater number of degenerating axons was found in the toneuronal connections is also seen in the spinal cord, VII of chimpanzees compared to macaques. In addition, where cortical axons project to progressively more caudal compared to macaques, the lateral subnucleus (motoneu- parts of the cord and penetrate further into the ventral rons of perioral muscles) of chimpanzees was more horn to reach motoneurons with increasing brain size in densely innervated by cortical axons and there appeared mammals (Striedter, 2005). to be a greater number of degenerating axons in the ipsi- Direct corticomotoneuronal connections might enhance lateral VII, especially in the lateral and dorsal subnuclei. the diversity and flexibility of motor behaviors. Increased Using the Nauta-Gygax technique to observe degenerat- corticospinal projections are correlated with some mea- ing fibers in human patients, Kuypers (1958b) reported the existence of direct cortical projections sures of manual dexterity in mammals (Heffner and Mas- to the VII, as well as the , nucleus terton, 1975, 1983; Iwaniuk et al., 1999) and the ability to ambiguus, and . These findings learn diverse vocalizations in birds is associated with the in humans are generally consistent with earlier anatomi- presence of direct connections between the telencephalon cal studies using the Marchi technique (Weidenhammer, and brainstem vocal motoneurons (Striedter, 1994). Nota- 1896; Hoche, 1898; Barnes, 1901) as well as a more recent bly, vocal abilities have recently been reported Nauta-Gygax study (Iwatsubo et al., 1990). Transcranial for elephants and dolphins (Janik, 2000; Poole et al., magnetic stimulation of unanesthetised human subjects 2005). These mammals have relatively enlarged neocorti- further supports the existence of a direct corticofacial ces, suggesting that they might also have direct cortical projection (Benecke et al., 1988). innervation of orofacial motoneurons. Current method- Silver impregnation techniques for degenerating axons, ological limitations, however, make this prediction diffi- however, are known to produce somewhat inconsistent cult to test. results (Heimer and RoBards, 1981). Importantly, the ex- Among catarrhine primates, behavioral observations istence of a direct corticofacial projection has been verified support the idea that greater direct corticofacial connec- in macaques using more reliable modern anterograde tions subserve enhanced volitional control of facial move- tract tracing methods (Jenny and Saper, 1987; Sokoloff ments. Great apes, but not monkeys, have been frequently and Deacon, 1990; Morecraft et al., 2001; Simonyan and observed to make nonemotional facial expressions seem- Ju¨ rgens, 2003) and antidromic recording of primary motor ingly for the purpose of play and self-amusement (van cortex after activation by VII stimulation (Sirisko and Lawick-Goodall, 1968; Chevalier-Skolnikoff, 1976, 1982). Sessle, 1983; Huang et al., 1988). Based on these studies, Additionally, although several species of anthropoids ap- macaques appear to have only sparse direct cortical pro- pear to have the capacity to inhibit voluntarily emotional jections from the primary motor cortex to the dorsal sub- vocalizations and facial expressions to deceive social part- nucleus (upper facial motoneurons) and strong projections ners (de Waal, 1982, 1986; Goodall, 1986; Byrne and to the lateral and ventrolateral regions of the VII (perioral Whiten, 1992), great apes and humans may be more motoneurons) (Jenny and Saper, 1987; Sokoloff and Dea- skilled at suppressing affective output for the purposes of con, 1990; Morecraft et al., 2001). In addition to these tactical deception (Yerkes and Yerkes, 1929; Chevalier- projections from primary motor cortex, other cortical mo- Skolnikoff, 1976, 1982; Whiten and Byrne, 1988; Byrne tor areas have been shown to innervate directly portions of and Whiten, 1992). Finally, the coordination of orofacial the VII in rhesus macaques (Morecraft et al., 1996, 2001). and laryngeal muscles in human probably requires 1076 SHERWOOD the existence of descending cortical control of motoneu- Andrew RJ. 1963b. The origin and evolution of the calls and facial rons (Deacon, 1997). expressions of the primates. Behaviour 20:1–109. Andrew RJ. 1965. The origins of facial expression. Sci Am 213:88–94. CONCLUSION Ashwell KW. 1982. The adult mouse facial nucleus: morphology and musculotopic organization. J Anat 135:531–538. Considering the involvement of superficial facial mus- Baisden RH, Woodruff ML, Whittington DL, Baker DC, Benson AE. cles in diverse behaviors ranging from blinking to the 1987. Cells of origin of the branches of the facial nerve: a retrograde negotiation of social networks, the anatomic organization HRP study in the rabbit. Am J Anat 178:175–184. of the VII within any given species reflects the combina- Banks GB, Noakes PG. 2002. Elucidating the molecular mechanisms tion of evolutionarily conservative organizational pro- that underlie the target control of motoneuron death. Int J Dev Biol grams as well as lineage-specific specializations. The gen- 46:551–558. eral musculotopic plan of the VII is consistent across all Barnes S. 1901. Degeneration in hemiplegia: with special reference to mammals, suggesting a link to early target-derived axon a ventrolateral pyramidal tract, the accessory fillet and Pick’s bun- dle. Brain 24:463–501. guidance cues. Nonetheless, interspecific variation in the Barton RA. 1999. The evolutionary ecology of the primate brain. In: relative distribution of motoneurons for different subsets Lee PC, editor. Comparative primate socioecology. Cambridge: of facial muscles demonstrates that specialization of the Cambridge University Press. p 167–203. periphery has an influence on the cytoarchitectural orga- Belford GR, Killackey HP. 1979. Vibrissae representation in subcor- nization of VII. tical trigeminal centers of the neonatal rat. J Comp Neurol 183: Although studies of the brainstem and midbrain affer- 305–322. ent connectivity of VII have not employed explicit compar- Benecke R, Meyer B-U, Scho¨nle P, Conrad B. 1988. Transcranial isons among species, these circuits regulate involuntary magnetic stimulation of the : responses in muscles activity of the facial muscles, such as protective reflexes supplied by cranial . Exp Brain Res 71:623–632. and orienting movements, and are likely to be similar Blinkov SM, Ponomarev VS. 1965. Quantitative determinations of neurons and glial cells in the nuclei of the facial and vestibular across species. In contrast, the development of direct neo- nerves in man, monkey, and dog. J Comp Neurol 125:295–302. cortical projections to the VII represents an important Blinkov SM, Glezer II. 1968. The human brain in figures and tables: anatomical substrate for the evolution of voluntary control a quantitative handbook. New York: Plenum Press. of the muscles of facial expression in Old World anthro- Bowden REM, Mahran ZY. 1956. The functional significance of the poid primates and may underlie complex facial behaviors pattern of innervation of the muscle quadratus labii superioris of in other lineages. the rabbit, cat, and rat. J Anat 90. Brodal A. 1981. Neurological anatomy: in relation to clinical medicine. ACKNOWLEDGMENTS New York: Oxford University Press. Byrne RW, Whiten A. 1992. Cognitive evolution in primates: Evidence The author thanks Drs. P.R. Hof, R.L. Holloway, J.M. from tactical deception. Man 27:609–627. Erwin, P.J. Gannon, and S.C. McFarlin for discussions Caton A, Hacker A, Naeem A, Livet J, Maina F, Bladt F, Klein R, that helped to formulate many of the ideas presented in Birchmeier C, Guthrie S. 2000. The branchial arches and HGF are this manuscript. 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