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. Author manuscript; available in PMC: 2020 Oct 15.
Published in final edited form as: J Comp Neurol. 2019 Apr 8;527(15):2599–2611. doi: 10.1002/cne.24693

The sensory thalamus and visual midbrain in mouse lemurs

Mansi P Saraf 1, Pooja Balaram 1,2, Fabien Pifferi 3, Henry Kennedy 4,5, Jon H Kaas 1
PMCID: PMC6688912  NIHMSID: NIHMS1525856  PMID: 30927368

Abstract

Mouse lemurs are the smallest of extant primates and are thought to resemble early primates in many ways. We provide histological descriptions of the major sensory nuclei of the dorsal thalamus and the superior colliculus of mouse lemurs (Microcebus murinus). The dorsal lateral geniculate nucleus has the six layers typical of strepsirrhine primates, with matching pairs of magnocellular, parvocellular, and koniocellular layers, one of each pair for each eye. Unlike most primates, magnocellular and parvocellular layers exhibit only small differences in cell size. All layers express VGLUT2, reflecting terminations of retinal inputs, and the expression of VGLUT2 is much less dense in the koniocellular layers. PV is densely expressed in all layers, while SMI-32 is densely expressed only in the magnocellular layers. The adjoining pulvinar complex has a posterior nucleus with strong VGLUT2 expression, reflecting terminations from the superior colliculus. The superior colliculus is laminated with dense expression of VGLUT2 in the upper superficial gray layer, reflecting terminations from the retina. The ventral (MGNv), medial (MGNm), and dorsal (MGNd) divisions of the medial geniculate complex are only moderately differentiated, although patches of dense VGLUT2 expression are found along the outer border of MGNv. The ventroposterior nucleus has darkly stained cells in Nissl stained sections, and narrow septa separating patchy regions of dense VGLUT2 expression that likely represent different body parts. Overall, these structures resemble those in other strepsirrhine primates, although they are smaller, with the sensory nuclei appearing to occupy proportionately more of the dorsal thalamus than in larger primates.

Keywords: lateral geniculate nucleus, medial geniculate nucleus, ventroposterior nucleus, pulvinar, primates, strepsirrhine, prosimian, RRID AB_2313581

Graphic Abstract

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Mouse lemurs are small primates that resemble early primates. We describe architecture features of thalamic sensory nuclei and the superior colliculus in VGLUT2, PV, SMI-32 and Nissl preparations. In general, the smaller sensory nuclei resemble those of other strepsirrhine primates. The layers of the LGN are especially distinguishable by VGLUT2.

INTRODUCTION

Here we describe the histochemical features of sensory nuclei of the dorsal thalamus, and the superior colliculus (SC) in mouse lemurs. Mouse lemurs are members of the lemur radiation of strepsirrhine primates in Madagascar. They are of special interest, not only because the strepsirrhine radiation has been understudied, but also because mouse lemurs have the smallest brains (about 2.5 grams) of all primates (Le Gros Clark, 1931). At around 1500 grams, human brains are roughly 600 times larger. Thus, mouse lemur brains, in comparison to those of other primates, are especially valuable in studies of how brain features vary across branches of primate evolution and differences in brain size. Since early primates were small, with small brains approaching those of mouse lemurs, mouse lemur brains may most closely resemble early primate brains. Overall, mouse lemurs have been considered to be a living model of early primates (Gebo, 2004; Martin, 1990).

Little is known about mouse lemur brains. The external appearance, cortical cytoarchitecture, and aspects of the dorsal thalamus of a single mouse lemur brain were first described by Le Gros Clark (1931). A more extensive study of cortical cytoarchitecture was published somewhat later (Zilles et al., 1980). More recently, our study of cortical architecture in mouse lemur (Saraf et al., 2019) was based on brain sections processed for cell bodies (Nissl or NeuN), the vesicular glutamate transporter 2 (VGLUT2), parvalbumin (PV), non-phosphorylated neurofilament (SMI-32), or cytochrome oxidase (CO). Thus, multiple histological procedures were used to define and characterize sensory and motor areas of cortex. Here, we used the same brain sections to identify and describe somatosensory, auditory, and visual nuclei of the dorsal thalamus, as well as the laminated structure of the superior colliculus. While the early description of the thalamus of a mouse lemur by Le Gros Clark (1931) was very brief, a more recent stereotaxic atlas of the mouse lemur brain provided photographs of Nissl stained sections through the thalamus as well as provided matching drawing indicating different nuclei (Bons et al., 1998). In the present study, our focus is on sensory nuclei because they are most reliably identified and have clear homologies across the primate order.

METHODS

We obtained four brains of adult mouse lemurs (Microcebus murinus) from the Brunoy colony (MNHN, FRANCE, license approval N° E91-114-1). All the experimental procedures were performed in accordance with the animal core and use guidelines established by the European Communities Council and National Institutes of Health. The methods have been described previously in our study of cortical sensory and motor areas from the same material (Saraf et al., 2019).

Tissue Acquisition

The mouse lemurs were euthanized and perfused with 2% or 4% paraformaldehyde (PFA) in 0.01M phosphate-buffer (PB) in the Kennedy lab in Lyon, France. After extraction, brains were shipped to the Kaas lab at Vanderbilt University. The brains were post-fixed in 4% PFA/0.01M PB, followed by cryoprotection in 30% sucrose in 0.1M phosphate buffer (PB) and then cut into 40μm sections in the coronal, sagittal or horizontal plane. Alternating series of sections were processed for cytochrome oxidase (CO; Wong-Riley, 1979) or Nissl with thionin, or stored in 0.05m TBS/AZ for immunohistochemistry.

Immunohistochemistry

Other brain sections were processed for immunohistochemical methods using NeuN (to label neuronal nuclei), VGLUT2 (to mark the vesicular glutamate transporter 2), parvalbumin (to mark excitatory projection neurons and their terminations), or SMI-32 (to label nonphosphorylated neurofilaments in excitatory neurons), as previously described (Balaram et al., 2013). For immunohistochemistry, sections were incubated in blocking solution for 2 hours prior to overnight incubation with the primary antibody. The following day, sections were rinsed several times in 0.01M PBS to remove excess primary antibody, and then incubated for 2 hours with the secondary antibody in a blocking solution. This was followed by overnight incubation in ABC solution dissolved in horse serum. After additional rinses in 0.01M PBS, sections were mounted on gelatin subbed slides, dehydrated, and coverslipped with Permount. All antibodies have been previously characterized in architectonic studies of primates (e.g., Wong and Kaas, 2010) and closely related non-primate species (e.g., Wong and Kaas, 2009). For more detailed information, please refer to Saraf et al. (2019).

Antibody Characterization

Anti-NeuN primary antibody: Mouse anti-NeuN, Catalog no. AB_177621 Millipore, Burlington MA. The immunogen is purified cell nuclei from mouse brain. This primary antibody was used in a concentration of 1:5000.

Anti-VGLUT2 primary antibody: antigen - vesicular glutamate transporter 2 (VGLUT2) recombinant protein from mouse VGLUT2 (Mouse anti VGLUT2, Cat# MAB5504, Millipore, Burlington MA; Immunogen is KLH-conjugated linear peptide). In Western Blots of primate neocortex, the antibody recognizes a 56-kDA bond, the molecular weight of VGLUT2 (Baldwin et al., 2013). This primary antibody was used in concentration of 1:5000.

Anti-PV primary antibody: antigen - calcium binding spot of PV (Mouse anti PV, Cat# P3088, Sigma-Aldrich, St. Louis MO). Immunogen of this antibody is frog muscle parvalbumin. This primary antibody was used in the concentration of 1:2000.

Anti-SMI-32 primary antibody: antigen- 200–kD non-phosphorylated epitope in neurofilament H (Mouse anti SMI-32, Cat# 801701, Bio Legend, San Diego CA; Immunogen is homogenized). The SMI-32 antibody labels neuronal cell bodies, dendrites and some thick axons, but not other cells and tissues (Hof & Morrison, 1995; Wong et al., 2009). The concentration of this primary antibody used was 1:2000.

Secondary antibody: The secondary against all the above primary antibodies was made in horse (Horse anti-mouse, Cat# BA-2000 also BA2000, Lot #RRID: AB_2313581, Vector Laboratories). The concentration used was 1:300.

Light Microscopy

Digital photomicrographs of cortical regions were acquired using a Nikon DXM1200 camera mounted on a Nikon E800 microscope (Nikon Inc., Melville NY). Images were adjusted for brightness and contrast using Adobe Photoshop (Adobe Systems Inc., San Jose CA) and figures were created using Adobe Illustrator (Adobe Systems Inc., San Jose CA).

RESULTS

The locations of midbrain and thalamic structures of interest in this study are shown in a horizontal brain section through the thalamus of a mouse lemur in Figure 1. The anterolateral limit of the thalamus is indicated by the thin, band-like reticular nucleus (RT) of the ventral thalamus. The most anterior part of the dorsal thalamus includes the ventral anterior nucleus at this level (Bons et al., 1998), followed by the large ventroposterior nucleus (VP) where neurons are more darkly stained, and where this nucleus has cell poor septal regions that separate the representations of body parts. The clearly laminated dorsal lateral geniculate nucleus (LGN) and the medial geniculate nucleus (MGN) are posterior and lateral to VP, close to where the dorsal thalamus transitions to the midbrain and to mainly the deeper layers of the superior colliculus in this section (Fig. 1). The more dorsal pulvinar complex is missing from this section. These structures are described more fully in the following parts of the Results. The dorsal thalamus of mouse lemurs is one of the smallest of primates (Stephan et al., 1984).

Figure 1.

Figure 1.

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The relative positions of sensory nuclei in a Nissl stained horizonal sections of the dorsal thalamus of mouse lemur. The thin reticular nucleus (RT) of the ventral thalamus marks the anterolateral border of the thalamus, and the ventral posterior nucleus (VP), dorsal lateral geniculate nuclei (LGN) and medial geniculate nuclei (MGN) stand out with their darkly stained cells. Midbrain structures, mostly the superior colliculus, make up the most posterior part of the section. Nissl stain. Anterior is towards the top of the sections. Scale bar is 1 mm.

The dorsal lateral geniculate nucleus (LGN)

The LGN is perhaps the most prominent nucleus of the mouse lemur thalamus (Fig. 1, 2 and 3). The darkly Nissl stained cells are clearly segregated in six distinctive layers (Fig. 2a) that are characteristic of all strepsirrhine primates (Kaas et al., 1978). As in galagos, lorises, and other lemurs, the LGN of mouse lemurs has three pairs of layers. Layer 1 and 2 form the magnocellular pair comprised of larger neurons than in the other layers, although the size differences in neurons of different layers are not as pronounced as in monkeys, apes, and humans (see Norden and Kaas, 1978). Layers 3 and 6 have somewhat smaller neurons, and are referred to as the parvocellular layers. Layers 4 and 5 have obviously smaller cells, and they are the koniocellular layers. The three sets of layers reflect the three processing channels from retina to cortex in primates and the two eyes (Casagrande, 1994). In strepsirrhine primates, layers 1, 5 and 6 get inputs for the contralateral eye, and are somewhat more extensive than layers 2, 3, and 4 for the ipsilateral eye, as the layers for the contralateral eye have a more extensive representation that includes the periphery of the contralateral visual hemifield (Kaas et al., 1972). Notice in the horizontal section of the LGN in Figure 2a, that layers 1, 5, and 6 extend further anterior than layers 2, 3, and 4 (top in the illustration) where peripheral vision is represented.

Figure 2.

Figure 2.

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Laminar characteristics of the dorsal lateral geniculate nucleus, LGN, in mouse lemur. In most preparations, the 6 layers of strepsirrhine primates can be identified. (a) A Nissl stained LGN from a horizontal brain section. Other sections are in the coronal (frontal) plane. (b) Vesicular glutamate transporter 2, VGLUT2. (c) SMI-32. (d) Parvalbumin, PV. Scale bar is 0.5 mm.

Figure 3.

Figure 3.

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Coronal brain sections show the relationships of the posterior pulvinar (pp) to the lateral geniculate nucleus (LGN) and the ventroposterior nucleus (VP). Note also the pregeniculate nucleus (PG) ventral to the LGN. Both (a) VGLUT2 and (b) SMI-32 levels are high in the pp, providing evidence for sensory activation by superior colliculus inputs. Scale bar is 1 mm.

The presence of dense VGLUT2 labeling in the LGN layers of mouse lemurs reflects the terminations and synapses of retinal inputs to those layers (Balaram et al., 2011). In mouse lemurs, the densest expression of the VGLUT2 antibody is in layers 1, 2, 3 and 6, the magnocellular and parvocellular layers (Fig. 2b). Less expression is apparent in layers 4 and 5, the koniocellular layers. The less dense expressions of the VGLUT2 protein in the koniocellular layers of the LGN is consistent with previous observations in strepsirrhine galagos (Balaram et al., 2011), suggesting that inputs from the retina less densely terminate in these layers (see Lachica and Casagrande, 1988). In SMI-32 preparations, layers 1 and 2 (magnocellular layers), are most densely labeled, layers 3 and 6 (parvocellular layers) are less dense, and layers 4 and 5 (koniocellular layers) are the least dense (Fig. 2c). The SMI-32 antibody stains the non-phosphorylated form of the intracellular neurofilament protein, and is most notably apparent in the larger pyramidal neurons in layers 3 and 5 of cortex (Hof & Morrison, 1995). As expected, the SMI-32 antibody labels the larger neurons of the M layers in the LGN of mouse lemurs most densely, the parvocellular layers less so, and the small neurons of the koniocellular layers the least. Finally, the antibody for parvalbumin also differentially labels classes of layers in the LGN of mouse lemurs. The PV antibody labels relay neurons and processes in the LGN layers of primates, especially of larger neurons in the magnocellular and parvocellular layers, and less so in koniocellular layers (Diamond et al., 1993; Johnson & Casagrande, 1995; Tigges & Tigges, 1991). However, in mouse lemurs, the staining for PV was high in all six layers (Fig. 2d; note that layers 1 and 2 are not very thick in this section).

In summary, the small lateral geniculate nucleus of mouse lemurs has the six layers found in the larger brains of other strepsirrhine primates, but the cells in the paired koniocellular, parvocellular, and magnocellular layer are less different in sizes. Nevertheless, the koniocellular layers are less darkly stained for VGLUT2 and SMI-32 as in other strepsirrhine primates. The koniocellular layers are more darkly stained for PV than in other strepsirrhine primates.

The pulvinar

The visual pulvinar of strepsirrhine primates consists of two main parts. The posterior part receives activating inputs from neurons in the inner superficial gray layer of the superior colliculus that are VGLUT2 positive. This posterior pulvinar of strepsirrhine primates corresponds to parts of the inferior pulvinar of monkeys (Baldwin et al., 2013). The more anterior and lateral part includes two large nuclei with inputs from V1 and V2 (Baldwin et al., 2017). Here, we focus on the posterior pulvinar (pp), as it can be clearly identified by VGLUT2 positive inputs. The posterior pulvinar is posterior and dorsal in the pulvinar complex of strepsirrhine primates, rather than inferior and medial, as are the VGLUT2 inputs in the inferior pulvinar of monkeys.

In mouse lemurs, the posterior pulvinar is also VGLUT2 positive (Fig. 3a). At the levels of the posterior half of the LGN, where the ventral posterior (VP) nucleus is still present, the posterior pulvinar caps the dorsolateral margin of the thalamus. In addition to being densely labeled with VGLUT2 (Fig. 3a), the posterior pulvinar also expresses SMI-32 (Fig. 3b). The posterior nucleus of the pulvinar extends to the posterior end of the dorsal thalamus, where the posterior nucleus is just lateral to the most anterior part of the superior colliculus, and dorsal to the medial geniculate complex (Fig. 4a). The posterior end of the posterior nucleus (Fig. 4b) is quite close to the superior colliculus. At this level, the posterior nucleus is nearly round, and the expression of VGLUT2 is very dense. At this dorsal and posterior location, the posterior nucleus is in its primitive position, where it is also found in rodents and tree shrews (Baldwin et al., 2017).

Figure 4.

Figure 4.

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The posterior pulvinar, pp, in coronal cut brain sections at the most posterior part of the thalamus processed for VGLUT2. Section (a) is slightly anterior to section (b). SC, superior colliculus. Scale bars are 1 mm in (a), and 0.5 mm in (b).

Figure 3 also shows portions of the pre-geniculate nucleus (PG), which is the ventral lateral geniculate nucleus (LGNv) of non-primate mammals (Jones, 2007; Niimi et al., 1963). The LGNv is a part of the ventral thalamus that has mainly visual connections and functions (see Nakamura and Itoha, 2004).

The superior colliculus

The laminar and sublaminar organization of the superior colliculus of mouse lemurs exhibits common mammalian characteristics and shares features with other strepsirrhine primates (Balaram et al., 2011; May, 2006). In the Nissl and NeuN processed sections though the superior colliculus of mouse lemurs, the superficial gray (sg) of densely packed neurons is just below a thin fibre layer, the stratum zonale (sz), on the surface of the superior colliculus (Fig. 5d). The sg is divided into an outer half with more scattered neurons, the upper superficial gray (usg), and an inner half of more densely packed neurons, the inner superficial gray (isg). The usg is especially dark in VGLUT2 preparations (Fig. 5b). In other strepsirrhine primates, this dense VGLUT2 label distinguishes inputs from the retina from the contralateral eye which terminate more superficially and more densely than those from the ipsilateral eye (Feig et al., 1992; Tigges & Tigges, 1970). The slightly less dark middle zone in the VGLUT2 label in the usg (Fig. 5b) may reflect a region of sparse terminations from both the ipsi- and the contralateral retina. The inner superficial gray, isg, has weak VGLUT2 labeling, but contains many neurons. Many of these isg neurons project to the posterior pulvinar with VGLUT2 positive terminations as in other strepsirrhine primates (Baldwin et al., 2013).

Figure 5.

Figure 5.

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The superior colliculus of mouse lemurs in sections cut in the coronal plane. The sections have been processed for (a) PV, (b) VGLUT2, (c) cytochrome oxidase, CO, or (d) neuron cell bodies, NeuN. The more superficial layers of the superior colliculus are identified in the inserts. stratum zonale (sz); upper superior gray layer (usg); inner superior gray layer (isg); stratum opticum (so). Scale bar is 0.5 mm.

In sections processed for PV, the usg is divided into three bands, much as in the sections processed for VGLUT2 (Fig. 5a). However, the isg staining for PV is relatively dense compared to the staining for VGLUT2. As the isg receives activating inputs from visual areas of cortex (Graham et al., 1979), the greater expression of PV than VGLUT2 in isg likely reflects the presence of PV positive terminations from visual cortex in isg as well as the lack of retinal terminations. Finally, as reported in galagos (Balaram et al., 2011) and other primates (Collins et al., 2005), the expression of cytochrome oxidase (CO) in mouse lemurs was highest in the sg and lower in the stratum opticum. The higher level in sg reflects the metabolic requirements of higher levels of neural activity by neurons with sensory inputs (Wong-Riley, 1979).

The medial geniculate complex

Although commonly referred to as a nucleus, the medial geniculate is actually a complex composed of three or more related nuclei (Hackett et al., 1998; Jones, 2007). In mouse lemurs, as in other mammals, the MGN complex is located in the posterior thalamus, immediately medial to the LGN (Fig. 1). Part of the nucleus extends past the posterior limit of the LGN to terminate ventral to the posterior pulvinar and the superior colliculus of the midbrain (Fig. 4a). More anterior in the complex, the ventral nucleus (MGNv) is identified by small, densely stained neurons in Nissl preparations (Fig. 6a), while the medial or magnocellular nucleus (MGNm) is composed of larger, more spaced neurons. The dorsal nucleus of the complex (MGNd) consists of smaller, less darkly stained neurons. In sections processed for VGLUT2, MGNv is the most darkly stained region, while MGNm and MGNd are more lightly stained (Fig. 6b). Patches on the outer border of MGNv are more darkly stained. In SMI-32 preparations, MGNm appears to be the most darkly stained, and MGNd is the lightest. MGNv is most dark along its outer border and moderately dark elsewhere. Both VGLUT2 and SMI-32 reflect driving inputs from the central nucleus of the inferior colliculus (Hackett et al., 2011), and these reaction products are especially dense along the outer edge of the MGNv in the most caudal extent of the nucleus (Fig. 7a and b). Four or five distinct clusters of dense VGLUT2 and SMI-32 labeling are located along the outer border while staining is much less dense throughout the rest of the MGN complex.

Figure 6.

Figure 6.

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The medial geniculate nucleus (MGN) complex of mouse lemurs. This auditory complex traditionally included the ventral nucleus of MGN, MGNv, the dorsal nucleus, MGNd, and the medial nucleus, MGNm. Brain sections cut in the frontal plane were processed for (a) Nissl; (b) VGLUT2; and (c) SMI-32. Scale bar is 0.5 mm.

Figure 7.

Figure 7.

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Dark patches in the medial geniculate nucleus (MGN) complex revealed by (a) VGLUT2 and (b) SMI-32. Note arrows. The sections were cut in the horizontal plane near the bottom of the MGN. Scale bar is 0.5 mm.

The somatosensory thalamus

The primary somatosensory nucleus in the thalamus is the ventroposterior nucleus, VP (Kaas, 2012). This nucleus is commonly divided into two parts, a medial part (VPM), that represents the head and mouth, and a lateral part that represents the rest of the body (VPL). Cell–poor septal regions separate VPM from VPL, as well as representations of digits and toes from each other in VPL and teeth, tongue and parts of the face in VPM (see Sawyer et al., 2015 for galagos). VPL and VPM neurons respond to light touch. The ventroposterior medial parvocellular nucleus, VPMpc, just medial to VPM, is involved in taste and touch on the tongue. The ventroposterior superior nucleus, VPS, just above VP, is involved in proprioception, while the ventroposterior inferior nucleus, VPI, has inputs from the spinothalamic system.

In horizontal brain sections through the thalamus of the mouse lemurs, VP is clearly evident in Nissl stains as a nucleus of darkly stained cells medial and somewhat anterior to the LGN (Fig. 1). Some thin septa are apparent that divide VPL into foot and hand territories, and further into clusters of neurons representing individual toes and digits. In frontal brain sections processed for VGLUT2 (Fig. 8b), the septa are more readily apparent, and a dorsoventral septum separates VPM from VPL. A more lateral dorsoventral septum separates the hand representation from the foot representation in other primates, while a most lateral group of VGLUT2 label marks the representation of the tail. More medial septa in VPM segregate groups of neurons devoted to facial whiskers, upper and lower face, teeth and tongue, but the identities of these septa have not been fully determined (Sawyer et al., 2015). These subdivisions of VP are much less apparent in sections processed for SMI-32 (Fig 8b). The expression of VGLUT2 is much less in VPMpc and in VPS than in VP (Fig. 8b). At this level of frontal sections, there is no evidence for the VPI, a nucleus of small neurons.

Figure 8.

Figure 8.

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Subdivisions of the somatosensory thalamus in mouse lemurs in coronal brain sections. (a) The expression of VGLUT2 in the VP (also see figure 3a). VP has two main divisions, medial (VPM) and lateral (VPL), marked by arrowheads. Stars mark a large cell-poor septum that separates VPM, representing the head, from VPL, representing the body. Another larger septum in VPL separates the hand representation next to VPM from the more lateral foot representation. Other septal regions separate smaller dense patches of VGLUT2 expression in VPM and VPL. Just medial and ventral to VPM, the parvocellular ventroposterior medical nucleus (VPMpc) for taste expresses less VGLUT2 than VPM and VPL. The lightly stained region over VPL is the ventroposterior superior nucleus, VPS. (b) A coronal brain section processed for SMI-32. VPMpc and VP are both darker than the VPS region. Scale bar is 0.5 mm.

DISCUSSION

Mouse lemur brains are of special interest as they are the smallest of primates, and they are thought to resemble the earliest of primates (Fleagle, 1999; Gebo, 2004; Le Gros Clark, 1931; Martin, 1990). Presently, there is a variety of lemur species in Madagascar. All these species likely evolved from a single ancestral species that was much like present day mouse lemurs, and that rafted from Africa to Madagascar some 60–70 mya (Horvath et al., 2008; Kappeler, 2000; Yoder et al., 1996). Due to recent fragmentation of the environment, a number of closely related and highly similar mouse lemur species have emerged (Hotaling et al., 2016). Overall, mouse lemurs remain the most widespread, abundant, and adaptive of the lemurs (Mittermeier et al., 1994; Richard & Dewar, 1991). Although they breed well in captivity, only small numbers now exist in breeding colonies. Mouse lemurs eat mainly insects, but also fruit, flowers, leaves, and sap. Mouse lemurs mature in about a year, and females have short gestation times, and usually give birth to twins.

We have previously described the sensory and motor areas of neocortex in mouse lemur brains (Saraf et al., 2019). The main findings are that primary sensory and motor areas can be identified by the histological criteria and that these cortical areas occupy much of neocortex, suggesting that mouse lemurs have fewer cortical areas than even small monkeys such as marmosets. Further studies could usefully determine if mouse lemurs have fewer cortical areas than other strepsirrhine primates with larger brains, as a relation between brain size and a number of cortical areas has been hypothesized for primates (Changizi & Shimojo, 2005; Kaas, 2000). As the dorsal thalamus provides the major subcortical inputs to neocortex, mouse lemurs may also have fewer nuclei in the thalamus.

There have been few previous studies of the organization of the thalamus in mouse lemurs, and none using a modern array of histological preparations. However, interest in the evolution of primate brains has long been high, as mouse lemurs are thought to resemble early primates. Thus, Le Gros Clark (1931) briefly described some nuclei of the thalamus from Nissl stained sections of a single brain, and compared these results with those obtained from other primates (Clark, 1932). In addition, Hassler (1966), Cooper et al. (1979), and McDonald et al. (1993) provided brief descriptions of the laminar organization of the dorsal geniculate nucleus of mouse lemurs. Here, we relate the sensory nuclei of the thalamus and the superior colliculus of mouse lemur to findings in other primates, especially galagos, the most studied strepsirrhine primate.

The visual thalamus

The dorsal lateral geniculate nucleus (LGN) and the visual pulvinar complex constitute the visual thalamus of mammals (Baldwin et al., 2017; Kaas et al., 1972). The mouse lemur has a LGN that closely resembles the lateral geniculate nuclei of other strepsirrhine primates (Kaas et al., 1978) in having six layers of three pairs, one for each eye of magnocellular (M), parvocellular (P) and koniocellular (K) layers. The LGN of a galago provides another example of this laminar arrangement (Fig. 9). The expression of VGLUT2 is greater in the koniocellular layers 4 and 5 in mouse lemurs than in galagos. In addition, the LGN of mouse lemurs is smaller than the LGN of other primates, and the differences in neuron sizes in the three types of layers are less pronounced. The LGN of mouse lemurs, for example, is one third the size of the galago LGN (see Stephan et al., 1984 for the LGN in these and other primates). In addition, as a nocturnal primate, the parvocellular layers are proportionately small, while the parvocellular layers in diurnal lemurs as well as diurnal monkeys are larger (Hassler, 1966). In monkeys, the parvocellular layers commonly subdivide to be counted as 4 or more, resulting in the common description of the primate LGN as having 6 layers (4 parvocellular and two magnocellular). However, strepsirrhine and haplorrhine primates do not have the same 6 layers. The parvocellular layers do not subdivide in some haplorrhine primates (owl monkeys, marmosets and gibbons), and the partly subdivided parvocellular layers in other haplorrhines are really only two complete layers (Kaas et al., 1978). As in other strepsirrhine primates, mouse lemurs have two well differentiated koniocellular layers. The well- developed koniocellular layers reflect the nocturnal origin of strepsirrhine primates, and these layers were reduced and lost as diurnal haplorrhine primates emerged, although K cells persist between layers. However, the only nocturnal monkey, the owl monkey, evolved a thick K cell region between the internal M and P layers, providing further evidence for the importance of K cell pathways for vision in dim light.

Figure. 9.

Figure. 9.

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The laminar features of the LGN of a galago (Otolemur garnettii; a) compared to a mouse lemur (b) in coronal brain sections. The section from the galago is Nissl stain, and the section from the mouse lemur is VGLUT2 stain. Layers 1 and 2 are the magnocellular layers, 3 and 6 are the parvocellular layers, and 4 and 5 are the koniocellular layers. The LGN in this galago is bigger than that of a mouse lemur, but very similar in appearance (also see figure 2a). Scale bar is 0.5 mm in (a) and (b).

In summary, the LGN of mouse lemurs reflects the probable features of the LGN of early primates, in that the LGN has only a limited neuron size specialization across the three classes of neurons. In addition, there is little expansion of the parvocellular layers, which represent a specialization for detailed form and color vision in daylight. Instead the koniocellular layers are expanded as they are functionally important in dim light, and are lost or reduced in diurnal primates (Casagrande, 1994).

Although part of the ventral thalamus, mouse lemurs also have a pre-geniculate nucleus, PG, which is found just ventral and anterior to the LGN (Fig. 3). PG is the homolog of the ventral lateral geniculate of other mammals (Jones, 2007; Niimi et al., 1963). In mouse lemurs and galagos, the PG retains the more primitive position of being ventral to the LGN, rather than anterior and over the LGN as in haplorrhine primates. The PG has retinal, cortical, tectal, and other connections and is thought to have roles in circadian rhythms and ocular motor functions (Kaas & Huerta, 1988).

The organization of the pulvinar complex of mouse lemurs is less well understood than the LGN. Based on more extensive information from the more fully studied galagos, we expect the visual pulvinar of mouse lemurs and other strepsirrhines to consist of three main components: the superior and inferior nuclei with retinotopic representations based on topographically organized inputs from primary visual cortex (Baldwin et al., 2017; Moore et al., 2019; Symonds & Kaas, 1978) and a nucleus or two with activating inputs from the superior colliculus (Baldwin et al., 2013). The superior representation corresponds to that of the lateral pulvinar (PL) of monkeys, while the inferior representation corresponds to the central lateral nucleus of the inferior pulvinar of monkeys, (PIcl) (Baldwin et al., 2017). In mouse lemurs, limited evidence based on injections of tracers in primary visual cortex, V1 or area 17, indicate that parts of the inferior pulvinar and superior pulvinar (the lateral pulvinar is mainly superior in strepsirrhine primates) project to V1 (Cooper et al., 1979). In monkeys, two different parts of the inferior pulvinar receive activating inputs from the superior colliculus, the posterior nucleus (PIp) and the central medial nucleus (PIcm) of the inferior colliculus that then project to temporal cortex. Due to their inputs from the superior colliculus, these two nuclei densely express VGLUT2. In galagos, and presumably in other strepsirrhine primates, dense VGLUT2 expression is limited to a single posterior part of the pulvinar, which is thought to be homologous with the posterior nucleus of the inferior pulvinar; Pip, of monkeys, or possibly Pip, fused with PIcm (Baldwin et al., 2013). Another nucleus of the inferior pulvinar, the medial nucleus PIm, has been identified histologically and by connections with visual area MT in monkeys (see Baldwin et al., 2017) and parts of the pulvinar complex of galagos project to MT (Wong & Kaas, 2010). However, a clear homologue of PIm has not been identified in galagos. The major contribution of the present study was to identify the posterior pulvinar nucleus, Pp, in mouse lemurs as the location of dense expression of VGLUT2. Other nuclei remain to be identified. The posterior nucleus of the pulvinar relays information on visual motion from the superior colliculus to temporal cortex in primates and other mammals (Baldwin et al., 2013).

In summary, the pulvinar complex in mouse lemurs has a posterior nucleus that is in a primitive position also found in galagos, tree shrews, and rodents (Baldwin et al., 2017). Based on connections with V1, the pulvinar also has two nuclei with retinotopic maps that are homologous to PL and PIcl maps in haplorrhine primates. The results provide further evidence that the posterior nucleus of early primates rotated ventrally and anterior to subdivide and become the Pip and PIcm nuclei of the inferior pulvinar of haplorrhine primates, while the superior and inferior retinotopic pulvinar maps of early primates rotated to form the PL and PIcl nuclei of haplorrhine primates. While all primates have cortical visual area MT, including mouse lemurs (Saraf et al., 2019), MT may have inputs from several places in the pulvinar of early primates rather than from a specific nucleus such as PIm (Moore et al., 2019).

The superior colliculus (SC)

The superior colliculus was included in this study as a major visual structure that projects to both the LGN and the posterior pulvinar. The superficial layers are highly visual in function, while deep layers are multisensory and motor (see Kaas and Huerta, 1988; May, 2006 for review). In mouse lemurs, the superficial and intermediate layers were identified by using NeuN to selectively label neurons. This revealed that the upper superficial gray, usg is less densely packed with neurons than the inner superficial gray, isgs. This difference occurs in other primates and it reflects, in part, the larger neurons in isgs (Kaas and Huerta, 1988). The outer superficial gray in other strepsirrhine primates receives inputs from the retina, with the denser inputs from the contralateral eye superficial to those from the ipsilateral eye (Feig et al., 1992; Symonds & Kaas, 1978; Tigges & Tigges, 1970). These retinal inputs express VGLUT2 in their synaptic terminals revealing a pattern in strepsirrhine galagos (Balaram et al., 2011) that closely resembles that of mouse lemurs (Fig. 5b). Thus, we have indirect evidence that the retinal inputs from the contralateral eye in mouse lemurs terminate in a somewhat denser manner in the superficial third of osg of mouse lemurs, while the retinal inputs from the ipsilateral eye terminate in the inner third of the osg. A narrow middle zone likely receives few terminations from either eye, while possibly having inputs from primary visual cortex (Symonds & Kaas, 1978). Somewhat surprisingly, the expression of parvalbumin, PV, in the superficial gray of mouse lemurs was very much like that of VGLUT2, suggesting that the density of PV also reflects retinal terminations. PV is often expressed in activating inputs to sensory cortex, as it is in layer 4 of primary visual cortex in galagos (Wong & Kaas, 2010) and in mouse lemurs (Saraf et al., 2019). Other areas of visual cortex project to deeper levels of the superficial gray (e.g., Graham et al., 1979) and the resulting high level of neural activity is reflected in the greater labeling of the superficial gray than the stratum opticum in CO preparations in mouse lemurs (Fig. 5c) and other primates, including galagos (Baldwin et al., 2013; Baldwin & Kaas, 2012). In rats and rabbits, parvalbumin is densely expressed in the neuropil of the SG of the SC (Barker & Dreher, 1998). PV is also expressed in a subset of inhibitory neurons in cortical and subcortical structures (Markram et al., 2004).

The medial geniculate complex

In mouse lemurs, the medial geniculate complex stands out as a more darkly stained structure in Nissl, VGLUT2, and SMI-32 preparations. In other mammals, three major divisions or nuclei are recognized as parts of the complex (Jones, 2007). These nuclei include a large ventral or principal nucleus, MGNv, a smaller dorsal nucleus, MGNd, and a medial magnocellular nucleus, MGNm. The large MGNv receives most of the inputs from the tonotopically organized central nucleus of the inferior colliculus, and in turn projects in a tonotopic pattern to primary areas of auditory cortex. MGNd and MGNm receive activating inputs from the dorsal cortex and shell of the inferior colliculus, and project more broadly to auditory and multisensory cortex. (e.g., Hackett et al., 1998; de la Mothe et al., 2006). These three nuclei were not as histologically distinct in mouse lemurs (Fig. 6), as they are in monkeys (de la Mothe et al., 2006; Hackett et al., 1998; Wong et al., 2010), and they more closely resemble the less distinct divisions of another strepsirrhine primate, galago (Wong & Kaas, 2010). Nissl stained brain sections have been used most commonly to identify nuclei of the auditory thalamus, and MGNv of mouse lemurs does have more densely packed, darkly stained cells. Higher levels of VGLUT2 expression helped define MGNv in mouse lemurs, and this higher expression has been demonstrated in MGNv of macaque monkeys (Hackett & de la Mothe, 2009) as a result of VGLUT2 positive inputs from the central nucleus of the inferior colliculus (Hackett et al., 2011). However, the patchy pattern of VGLUT2 terminations in MGNv in mouse lemurs has not been described before. This may reflect a specialization of the smaller MGN complex in mouse lemurs. VGLUT2 was less densely expressed in MGNd and MGNm in mouse lemurs, as in macaque monkeys (Hackett & de la Mothe, 2009). Finally, while SMI-32 preparations have not been commonly used in studies of the histology of the MGN complex, sections processed for SMI-32 usefully distinguished MGNv as a more darkly stained nucleus than MGNm and especially MGNd in mouse lemurs (Fig. 6c), and labeled dense patches along the outer border of MGNv that closely resemble those labeled by VGLUT2 (Fig. 7).

The somatosensory thalamus

The ventroposterior nucleus, VP, is part of the system that receives information about low threshold mechanoreceptors in the skin from the dorsal column nuclei of the brainstem and upper spinal cord and relays to VP and to primary and secondary areas of somatosensory cortex (Kaas, 2012). The ventroposterior nucleus is commonly divided into a medial subnucleus, VPM, representing the face and mouth, and a lateral subnucleus, VPL, representing the rest of the body. Other parts of the somatosensory thalamus include the parvocellular ventroposterior medial nucleus, VPMpc, for taste, the ventroposterior superior nucleus, VPS, for proprioception, and the ventroposterior inferior nucleus, VPI, with spinothalamic inputs that respond to noxious and tactile stimulation. VP often has clear subdivisions where groups of cells are separated by narrow, nearly cell free septa (Welker, 1973). The most consistent cell–poor band of fibers separates VPM from VPL, but both major divisions of VP have other septa separating other cell-groups, representing fingers and toes, but also for parts of the face (Rausell & Jones, 1991). In rats and mice, individual whiskers of the face are represented in groups of cells called barreloids that are separated by surrounding septa (Van Der Loos, 1976).

In mouse lemurs, narrow septa are weakly apparent in Nissl preparations through VP, but not nearly as clearly as in other primates. The septa are also only weakly apparent in SMI-32 preparations, but many more are obvious in sections processed for VGLUT2 (Fig. 8). Judging from the positions of these septa, one likely separates VPM from VPL, and another separates hand from foot representations. The significances of other septa are less clear. In related strepsirrhine galagos, the septa are more obvious in Nissl, CO, PV and VGLUT2 preparations than in mouse lemurs, and groups of cells representing each of the digits are clearly separated by septa in a pattern that is similar to those in monkeys (Qi et al., 2011). More recently, the representations of body parts in VP of galagos was shown more clearly in brain sections cut in a nearly horizontal plane (Sawyer et al., 2015), and major septa separating head, hand and foot representations were obvious in VGLUT2 preparations. In addition, septa in the foot representation of galagos likely separate representations of the toes. Most importantly, the sections revealed an array of barreloid-like modules in the face representation in VPM that likely represent individual facial whiskers. While modular subdivisions of VPM were visible in our coronal brain sections through VPM of mouse lemurs, their significance is unclear, and our horizontal sections were too few to reveal a whisker like pattern in VGLUT2 sections.

As for other somatosensory nuclei, VPMpc and VPS less densely expressed VGLUT2 than VPM, as in monkeys (Qi et al., 2011). There was very little of what could be referred to as VPI immediately ventral to VP in mouse lemurs although traces of VPI were suggested in and under septal regions of VP. VPI is not a nucleus that is definitively part of the somatosensory thalamus in most mammals. Instead, spinothalamic axons terminate in a nucleus posterior to VP in rodents and other mammals (Ebner & Kaas, 2015), as they also do in addition to VPI in monkeys (Stepniewska et al., 2003). Possibly, VPI is more posterior in mouse lemurs. The spinothalamic inputs in galagos appear to terminate in caudal VP (Pearson & Haines, 1980).

Conclusions

Although the dorsal thalamus appears to be smaller in mouse lemurs than in other primates, the nuclei of the visual, auditory, and somatosensory thalamus can be readily identified and subdivided especially in brain sections processed for VGLUT2 expressions. The lateral geniculate nucleus has the pairs of koniocellular, parvocellular, and magnocellular layers of larger strepsirrhine primates, although the differences in sizes of neurons in these layers are less marked. The posterior nucleus of the inferior pulvinar can be identified by dense VGLUT2 positive inputs from the superior colliculus. In mouse lemurs the posterior pulvinar (pp) is in more the primitive dorsal-caudal position found in strepsirrhine primates. The ventroposterior nucleus has cell-poor septal regions separating cell groups related to different body parts, but except for the face representations in VPM and hand and foot regions in VPL, the significances of septal regions are unclear. Overall, the thalamic nuclei and their overall layout resemble those of other strepsirrhine primates, and in size likely resemble nuclei of early primates, which were also small and nocturnal.

ACKNOWLEDGEMENT:

This research was supported by National Institute of Health, EY002686 and EY025422 (J. H. K.). LABEX CORTEX (ANR-11-LABX-0042) of Université de Lyon, (ANR-11-IDEX-0007) operated by the French National Research Agency (ANR) (H. K.), ANR-14-CE13–0033, ARCHI-CORE (H. K.), ANR-15-CE32–0016, CORNET (H. K.)., the CNRS (P. F.), MNHN (PF) and GIS IBISA (P. F.).

DATA AVAILABILITY STATEMENT:

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Footnotes

CONFLICTS OF INTEREST STATEMENT:

None of the authors has any known or potential conflicts of interest to declare with respect to the publication of this work.

REFERENCES

  1. Balaram P, Hackett TA, & Kaas JH (2013). Differential expression of vesicular glutamate transporters 1 and 2 may identify distinct modes of glutamatergic transmission in the macaque visual system. J Chem Neuroanat, 50–51, 21–38. doi: 10.1016/j.jchemneu.2013.02.007 [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Balaram P, Takahata T, & Kaas JH (2011). VGLUT2 mRNA and protein expression in the visual thalamus and midbrain of prosimian galagos (Otolemur garnetti). Eye Brain, 2011(3), 5–15. doi: 10.2147/EB.S16998 [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baldwin MK, Balaram P, & Kaas JH (2013). Projections of the superior colliculus to the pulvinar in prosimian galagos (Otolemur garnettii) and VGLUT2 staining of the visual pulvinar. J Comp Neurol, 521(7), 1664–1682. doi: 10.1002/cne.23252 [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baldwin MK, & Kaas JH (2012). Cortical projections to the superior colliculus in prosimian galagos (Otolemur garnetti). J Comp Neurol, 520(9), 2002–2020. doi: 10.1002/cne.23025 [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Baldwin MKL, Balaram P, & Kaas JH (2017). The evolution and functions of nuclei of the visual pulvinar in primates. J Comp Neurol, 525(15), 3207–3226. doi: 10.1002/cne.24272 [DOI] [PubMed] [Google Scholar]
  6. Barker DA, & Dreher B (1998). Spatiotemporal patterns of ontogenetic expression of parvalbumin in the superior colliculi of rats and rabbits. J Comp Neurol, 393(2), 210–230. [DOI] [PubMed] [Google Scholar]
  7. Bons N, Silhol S, Barbie V, Mestre-Frances N, & Albe-Fessard D (1998). A stereotaxic atlas of the grey lesser mouse lemur brain (Microcebus murinus). Brain Res Bull, 46(1–2), 1–173. [DOI] [PubMed] [Google Scholar]
  8. Casagrande VA (1994). A third parallel visual pathway to primate area V1. Trends Neurosci, 17(7), 305–310. [DOI] [PubMed] [Google Scholar]
  9. Changizi MA, & Shimojo S (2005). Parcellation and area-area connectivity as a function of neocortex size. Brain Behav Evol, 66(2), 88–98. doi: 10.1159/000085942 [DOI] [PubMed] [Google Scholar]
  10. Clark WE (1932). A Morphological Study of the Lateral Geniculate Body. Br J Ophthalmol, 16(5), 264–284. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Collins CE, Hendrickson A, & Kaas JH (2005). Overview of the visual system of Tarsius. Anat Rec A Discov Mol Cell Evol Biol, 287(1), 1013–1025. doi: 10.1002/ar.a.20263 [DOI] [PubMed] [Google Scholar]
  12. Cooper HM, Kennedy H, Magnin M, & Vital-Durand F (1979). Thalamic projections to area 17 in a prosimian primate, Microcebus murinus. J Comp Neurol, 187(1), 145–167. doi: 10.1002/cne.901870109 [DOI] [PubMed] [Google Scholar]
  13. de la Mothe LA, Blumell S, Kajikawa Y, & Hackett TA (2006). Thalamic connections of the auditory cortex in marmoset monkeys: core and medial belt regions. J Comp Neurol, 496(1), 72–96. doi: 10.1002/cne.20924 [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Diamond IT, Fitzpatrick D, & Schmechel D (1993). Calcium binding proteins distinguish large and small cells of the ventral posterior and lateral geniculate nuclei of the prosimian galago and the tree shrew (Tupaia belangeri). Proc Natl Acad Sci U S A, 90(4), 1425–1429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ebner FF, & Kaas JH (2015). Somatosensory System In Paxinos G (Ed.), The Rat Nervous System (Fourth edition ed., pp. 675–701): Elsevier Inc. [Google Scholar]
  16. Feig S, Van Lieshout DP, & Harting JK (1992). Ultrastructural studies of retinal, visual cortical (area 17), and parabigeminal terminals within the superior colliculus of Galago crassicaudatus. J Comp Neurol, 319(1), 85–99. doi: 10.1002/cne.903190109 [DOI] [PubMed] [Google Scholar]
  17. Fleagle JG (1999). Primate adaptation and evolution San Diego, CA: Elsevier. [Google Scholar]
  18. Gebo DL (2004). A shrew-sized origin for primates. Am J Phys Anthropol, Suppl 39, 40–62. doi: 10.1002/ajpa.20154 [DOI] [PubMed] [Google Scholar]
  19. Graham J, Lin CS, & Kaas JH (1979). Subcortical projections of six visual cortical areas in the owl monkey, Aotus trivirgatus. J Comp Neurol, 187(3), 557–580. doi: 10.1002/cne.901870307 [DOI] [PubMed] [Google Scholar]
  20. Hackett TA, & de la Mothe LA (2009). Regional and laminar distribution of the vesicular glutamate transporter, VGluT2, in the macaque monkey auditory cortex. J Chem Neuroanat, 38(2), 106–116. doi: 10.1016/j.jchemneu.2009.05.002 [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hackett TA, Stepniewska I, & Kaas JH (1998). Thalamocortical connections of the parabelt auditory cortex in macaque monkeys. J Comp Neurol, 400(2), 271–286. [DOI] [PubMed] [Google Scholar]
  22. Hackett TA, Takahata T, & Balaram P (2011). VGLUT1 and VGLUT2 mRNA expression in the primate auditory pathway. Hear Res, 274(1–2), 129–141. doi: 10.1016/j.heares.2010.11.001 [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Hassler R (1966). Comparative anatomy of the central visual systems in day and night active primates In Hassler R & Stephen S (Eds.), Evolution of the Forebrain (pp. 419–434). Stuttgart, Germany: Thieme Medical Publishers. [Google Scholar]
  24. Hof PR, & Morrison JH (1995). Neurofilament protein defines regional patterns of cortical organization in the macaque monkey visual system: a quantitative immunohistochemical analysis. J Comp Neurol, 352(2), 161–186. doi: 10.1002/cne.903520202 [DOI] [PubMed] [Google Scholar]
  25. Horvath JE, Weisrock DW, Embry SL, Fiorentino I, Balhoff JP, Kappeler P, … Yoder AD (2008). Development and application of a phylogenomic toolkit: resolving the evolutionary history of Madagascar’s lemurs. Genome Res, 18(3), 489–499. doi: 10.1101/gr.7265208 [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hotaling S, Foley ME, Lawrence NM, Bocanegra J, Blanco MB, Rasoloarison R, … Weisrock DW (2016). Species discovery and validation in a cryptic radiation of endangered primates: coalescent-based species delimitation in Madagascar’s mouse lemurs. Mol Ecol, 25(9), 2029–2045. doi: 10.1111/mec.13604 [DOI] [PubMed] [Google Scholar]
  27. Johnson JK, & Casagrande VA (1995). Distribution of calcium-binding proteins within the parallel visual pathways of a primate (Galago crassicaudatus). J Comp Neurol, 356(2), 238–260. doi: 10.1002/cne.903560208 [DOI] [PubMed] [Google Scholar]
  28. Jones EG (2007). The Thalamus. New York, NY: Cambridge University Press. [Google Scholar]
  29. Kaas JH (2000). Why is Brain Size so Important: Design Problems and Solutions as Neocortex Gets Biggeror Smaller. Brain and Mind, 1(1), 7–23. [Google Scholar]
  30. Kaas JH (2012). Somatosensory System In Mai J & Paxinos G (Eds.), The Human Nervous System (Third ed., pp. 1064–1099). Oxford: Elsevier. [Google Scholar]
  31. Kaas JH, Guillery RW, & Allman JM (1972). Some principles of organization in the dorsal lateral geniculate nucleus. Brain Behav Evol, 6(1), 253–299. doi: 10.1159/000123713 [DOI] [PubMed] [Google Scholar]
  32. Kaas JH, & Huerta MF (1988). Subcortical visual system of primate In Steklis HP (Ed.), Comparative Primate Biology: Neuroscience (pp. 327–391). New York: Alan R. Liss, Inc. [Google Scholar]
  33. Kaas JH, Huerta MF, Weber JT, & Harting JK (1978). Patterns of retinal terminations and laminar organization of the lateral geniculate nucleus of primates. J Comp Neurol, 182(3), 517–553. doi: 10.1002/cne.901820308 [DOI] [PubMed] [Google Scholar]
  34. Kappeler PM (2000). Lemur origins: rafting by groups of hibernators? Folia Primatol (Basel), 71(6), 422–425. doi: 10.1159/000052741 [DOI] [PubMed] [Google Scholar]
  35. Lachica EA, & Casagrande VA (1988). Development of primate retinogeniculate axon arbors. Vis Neurosci, 1(1), 103–123. [DOI] [PubMed] [Google Scholar]
  36. Le Gros Clark WE (1931). The brain of Microcebus murinus. Journal of Zoology, 101(2), 463–486. [Google Scholar]
  37. Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, & Wu C (2004). Interneurons of the neocortical inhibitory system. Nat Rev Neurosci, 5(10), 793–807. doi: 10.1038/nrn1519 [DOI] [PubMed] [Google Scholar]
  38. Martin RD (1990). Primate Origins and Evolution (First ed.). Princeton, NJ: Princeton University Press. [Google Scholar]
  39. May PJ (2006). The mammalian superior colliculus: laminar structure and connections. Prog Brain Res, 151, 321–378. doi: 10.1016/S0079-6123(05)51011-2 [DOI] [PubMed] [Google Scholar]
  40. McDonald CT, McGuinness ER, & Allman JM (1993). Laminar organization of acetylcholinesterase and cytochrome oxidase in the lateral geniculate nucleus of prosimians. Neuroscience, 54(4), 1091–1101. [DOI] [PubMed] [Google Scholar]
  41. Mittermeier RA, Tattersall I, R. KW, Meyers DM, & Mast RQ (1994). Lemurs of Madagascar: Conservation International Tropical Field Guide Series (First Edition ed.). Washington, DC: Conservation International. [Google Scholar]
  42. Moore B, Li K, Kaas JH, Liao CC, Boal AM, Mavity-Hudson J, & Casagrande V (2019). Cortical projections to the two retinotopic maps of primate pulvinar are distinct. J Comp Neurol, 527(3), 577–588. doi: 10.1002/cne.24515 [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Nakamura H, & Itoh K (2004). Cytoarchitectonic and connectional organization of the ventral lateral geniculate nucleus in the cat. J Comp Neurol, 473(4), 439–462. doi: 10.1002/cne.20074 [DOI] [PubMed] [Google Scholar]
  44. Niimi K, Kanaseki T, & Takimoto T (1963). The Comparative Anatomy of the Ventral Nucleus of the Lateral Geniculate Body in Mammals. J Comp Neurol, 121, 313–323. [DOI] [PubMed] [Google Scholar]
  45. Norden JJ, & Kaas JH (1978). The identification of relay neurons in the dorsal lateral geniculate nucleus of monkeys using horseradish peroxidase. J Comp Neurol, 182(4), 707–725. doi: 10.1002/cne.901820409 [DOI] [PubMed] [Google Scholar]
  46. Pearson JC, & Haines DE (1980). Somatosensory thalamus of a prosimian primate (Galago senegalensis). I. Configuration of nuclei and termination of spinothalamic fibers. J Comp Neurol, 190(3), 533–558. doi: 10.1002/cne.901900309 [DOI] [PubMed] [Google Scholar]
  47. Qi HX, Gharbawie OA, Wong P, & Kaas JH (2011). Cell-poor septa separate representations of digits in the ventroposterior nucleus of the thalamus in monkeys and prosimian galagos. J Comp Neurol, 519(4), 738–758. doi: 10.1002/cne.22545 [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Rausell E, & Jones EG (1991). Histochemical and immunocytochemical compartments of the thalamic VPM nucleus in monkeys and their relationship to the representational map. J Neurosci, 11(1), 210–225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Richard AF, & Dewar RE (1991). Lemur Ecology. Annual Review of Ecology and Systematics, 22(1), 145–175. [Google Scholar]
  50. Saraf MP, Balaram P, Pifferi F, Gamanut R, Kennedy H, & Kaas JH (2019). Architectonic features and relative locations of primary sensory and related areas of neocortex in mouse lemurs. J Comp Neurol, 527(3), 625–639. doi: 10.1002/cne.24419 [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Sawyer EK, Liao CC, Qi HX, Balaram P, Matrov D, & Kaas JH (2015). Subcortical barrelette-like and barreloid-like structures in the prosimian galago (Otolemur garnetti). Proc Natl Acad Sci U S A, 112(22), 7079–7084. doi: 10.1073/pnas.1506646112 [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Stephan H, Frahm HD, & Baron G (1984). Comparison of brain structure volumes in insectivora and primates. IV. Non-cortical visual structures. J Hirnforsch, 25(4), 385–403. [PubMed] [Google Scholar]
  53. Stepniewska I, Sakai ST, Qi HX, & Kaas JH (2003). Somatosensory input to the ventrolateral thalamic region in the macaque monkey: potential substrate for parkinsonian tremor. J Comp Neurol, 455(3), 378–395. doi: 10.1002/cne.10499 [DOI] [PubMed] [Google Scholar]
  54. Symonds LL, & Kaas JH (1978). Connections of striate cortex in the prosimian, Galago senegalensis. J Comp Neurol, 181(3), 477–512. doi: 10.1002/cne.901810304 [DOI] [PubMed] [Google Scholar]
  55. Tigges M, & Tigges J (1970). The retinofugal fibers and their terminal nuclei in Galago crassicaudatus (primates). J Comp Neurol, 138(1), 87–101. doi: 10.1002/cne.901380107 [DOI] [PubMed] [Google Scholar]
  56. Tigges M, & Tigges J (1991). Parvalbumin immunoreactivity of the lateral geniculate nucleus in adult rhesus monkeys after monocular eye enucleation. Vis Neurosci, 6(4), 375–382. [DOI] [PubMed] [Google Scholar]
  57. Van Der Loos H (1976). Barreloids in mouse somatosensory thalamus. Neurosci Lett, 2(1), 1–6. [DOI] [PubMed] [Google Scholar]
  58. Welker WI (1973). Principles of organization of the ventrobasal complex in mammals. Brain Behav Evol, 7(4), 253–336. doi: 10.1159/000124417 [DOI] [PubMed] [Google Scholar]
  59. Wong P, Collins CE, Baldwin MK, & Kaas JH (2009). Cortical connections of the visual pulvinar complex in prosimian galagos (Otolemur garnetti). J Comp Neurol, 517(4), 493–511. doi: 10.1002/cne.22162 [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Wong P, Collins CE, & Kaas JH (2010). Overview of Sensory Systems of Tarsius. International Journal of Primatology, 31(6), 1002–1031. [Google Scholar]
  61. Wong P, & Kaas JH (2009). Architectonic subdivisions of neocortex in the tree shrew (Tupaia belangeri). Anat Rec (Hoboken), 292(7), 994–1027. doi: 10.1002/ar.20916 [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Wong P, & Kaas JH (2010). Architectonic subdivisions of neocortex in the Galago (Otolemur garnetti). Anat Rec (Hoboken), 293(6), 1033–1069. doi: 10.1002/ar.21109 [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Wong-Riley M (1979). Changes in the visual system of monocularly sutured or enucleated cats demonstrable with cytochrome oxidase histochemistry. Brain Res, 171(1), 11–28. [DOI] [PubMed] [Google Scholar]
  64. Yoder AD, Cartmill M, Ruvolo M, Smith K, & Vilgalys R (1996). Ancient single origin for Malagasy primates. Proc Natl Acad Sci U S A, 93(10), 5122–5126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  65. Zilles K, Zilles B, & Schleicher A (1980). A quantitative approach to cytoarchitectonics. VI. The areal pattern of the cortex of the albino rat. Anat Embryol (Berl), 159(3), 335–360. [DOI] [PubMed] [Google Scholar]

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