Cortical Afferents of Area 10 in Cebus Monkeys: Implications for the Evolution of the Frontal Pole.

Area 10, located in the frontal pole, is a unique specialization of the primate cortex. We studied the cortical connections of area 10 in the New World Cebus monkey, using injections of retrograde tracers in different parts of this area. We found that injections throughout area 10 labeled neurons in a consistent set of areas in the dorsolateral, ventrolateral, orbital, and medial parts of the frontal cortex, superior temporal association cortex, and posterior cingulate/retrosplenial region. However, sites on the midline surface of area 10 received more substantial projections from the temporal lobe, including clear auditory connections, whereas those in more lateral parts received >90% of their afferents from other frontal areas. This difference in anatomical connectivity reflects functional connectivity findings in the human brain. The pattern of connections in Cebus is very similar to that observed in the Old World macaque monkey, despite >40 million years of evolutionary separation, but lacks some of the connections reported in the more closely related but smaller marmoset monkey. These findings suggest that the clearer segregation observed in the human frontal pole reflects regional differences already present in early simian primates, and that overall brain mass influences the pattern of cortico-cortical connectivity.

Genetic variability of the sws1 cone opsin gene among New World monkeys.

Vision is a major sense for Primates and the ability to perceive colors has great importance for the species ecology and behavior. Visual processing begins with the activation of the visual opsins in the retina, and the spectral absorption peaks are highly variable among species. In most Primates, LWS/MWS opsins are responsible for sensitivity to long/middle wavelengths within the visible light spectrum, and SWS1 opsins provide sensitivity to short wavelengths, in the violet region of the spectrum. In this study, we aimed to investigate the genetic variation on the sws1 opsin gene of New World monkeys (NWM) and search for amino acid substitutions that might be associated with the different color vision phenotypes described for a few species. We sequenced the exon 1 of the sws1 opsin gene of seven species from the families Callitrichidae, Cebidae, and Atelidae, and searched for variation at the spectral tuning sites 46, 49, 52, 86, 90, 93, 114, 116, and 118. Among the known spectral tuning sites, only residue 114 was variable. To investigate whether other residues have a functional role in the SWS1 absorption peak, we performed computational modeling of wild-type SWS1 and mutants A50I and A50V, found naturally among the species investigated. Although in silico analysis did not show any visible effect caused by these substitutions, it is possible that interactions of residue 50 with other sites might have some effect in the spectral shifts in the order of ~14 nm, found among the NWM. We also performed phylogenetic reconstruction of the sws1 gene, which partially recovered the species phylogeny. Further studies will be important to uncover the mutations responsible for the phenotypic variability of the SWS1 of NWM, and how spectral tuning may be associated with specific ecological features such as preferred food items and habitat use.

Tangential distribution of cell type and direction selectivity in monkey area MT.

We studied the multiunit responses to moving and static stimuli from 585 cell clusters in area MT using multi-electrode arrays. Our aim was to explore if MT columns exhibit any larger-scale tangential organization or clustering based on their response properties. Neurons showing both motion and orientation selectivity were classified into four categories: 1- Type I (orientation selectivity orthogonal to the axis of motion); 2- Type II (orientation selectivity coaxial to the axis of motion); 3- Type DS (significant response to moving stimuli, but non-significant response to static stimuli); and 4- Type OS (significant orientation selectivity, but non-significant direction selectivity). Type I (34%), Type II (24%) and Type DS (32%) clusters were the most predominant and may be associated with different stages of motion processing in MT. On the other hand, the rarer Type OS (9%) may be integrating motion and form processing. Type I and unidirectional sites were the only classes to exhibit significant clustering. Type OS sites showed a trend for clustering, which did not reach statistical significance. We also found a trend for unidirectional sites to have bidirectional sites as neighbors. In conclusion, neuronal clustering associated with these four categories may be related to distinct MT functional circuits.

Introduction.

The pulvinar can be subdivided into well-delimitated regions based on chemoarchitectural, cytoarchitectural, myeloarchitectural, connectivity, and electrophysiological criteria. Subdivisions of the pulvinar based on its chemoarchitectural features are the most consistently preserved across species of New and Old World monkeys. It is reasonable to speculate that the occurrence and distribution of calcium-binding proteins in the pulvinar, such as calbindin and parvalbumin, have been preserved along evolution. Therefore, they have proven to be valuable tools capable of probing the basic pulvinar scaffold across primate species. Along this review, we will provide an overview of the available data regarding the various subdivisions of the pulvinar that have been proposed based on architectural criteria such as the distribution of molecular markers, neuronal morphology, and fiber layout.

Cytoarchitecture and Myeloarchitecture of the Pulvinar.

In this chapter, we discuss the different ways in which the primate pulvinar has been subdivided, based on cytoarchitectural and myeloarchitectural criteria. One original criterion, based on cytoarchitecture, subdivided the pulvinar into nucleus pulvinaris medialis (PM), nucleus pulvinaris lateralis (PL), and nucleus pulvinaris inferior (PI). Later, the anterior limits of the pulvinar were extended and a subdivision was added to this nucleus, named pulvinar oralis (PO). PO occupies the anterior portion of the pulvinar and appears between the nucleus centrum medianum (CM) and the nucleus ventralis posterior lateralis (VPL).

Chemoarchitecture of the Pulvinar.

Cytochemical and immunocytochemical methods reveal details of the pulvinar architecture that are not apparent from Nissl and myelin staining. The results of these techniques have been interpreted in different ways by different investigators, each adopting different sets of nomenclature for the various pulvinar subdivisions. In this chapter, we discuss the notion that the differentiation of the pulvinar along primate evolution took place upon a relatively rigid chemoarchitectonic scaffold.

Visual Map Representations in the Primate Pulvinar.

The pulvinar receives direct visual information from the retina and indirect visual information from several cortical and subcortical areas. In this chapter, we discuss the visuotopic organization of the primate pulvinar. Electrophysiological techniques have been systematically employed to study pulvinar visuotopy in the owl, capuchin, and macaque monkeys. A single map of the visual field has been described in the pulvinar of the owl monkey, while two independent maps have been described in the capuchin and macaque pulvinar.

Connectivity of the Pulvinar.

Pulvinar connectivity has been studied using a variety of neuroanatomical tracing techniques in both New and Old World monkeys. Connectivity studies have revealed additional maps of the visual field other than those described using electrophysiological techniques, such as P3 in the capuchin monkey and P3/P4 in the macaque monkey. In this chapter, we argue that with increasing cortical size, the pulvinar developed new functional subdivisions in order to effectively interconnect and interact with the cortex.

Reestablishing the Chemoarchitectural Borders Based on Electrophysiological and Connectivity Data.

In this chapter, we discuss the poor agreement between visuotopic maps described using electrophysiological and connectivity data and the subdivisions of the pulvinar based on chemoarchitecture. We focus on the differences and similarities between New and Old World monkeys to evaluate how this agreement evolved during evolution. There is some agreement in the localization of P1, described using electrophysiological and connectivity data, and the lateral and central portions of the nucleus pulvinaris inferior (PI), defined based on chemoarchitectural criteria. Similarly, there is some colocalization between P3 and the medial portion of PI in both New and Old World monkeys. One difference between primates refers to P2, which is present in the Old World macaque monkey but absent in the New World monkeys. P4, which has not been studied in all primates, shows a partial spatial agreement with the dorsal portion of the chemoarchitecturally defined PL.

Visual Topography of the Pulvinar Projection Zones.

In this chapter, we describe the visuotopy of the pulvinar subdivisions P1, P2, and P4. In all primates, P1 colocalizes with the chemoarchitecturally defined PI and a small portion of PL. The peripheral visual field is represented anteriorly in the medial portion of PI, while central vision is represented more posteriorly in the medial portion of PL. The vertical meridian representation is located on the lateral edge of P1, while the horizontal meridian is represented obliquely from the lateral to the medial extent of P1. The upper visual field is represented ventrally, while the lower field is located dorsally. P2 has only been described in the macaque monkey. It contains a representation of the peripheral visual field, located in its anterior portion, and of the central field, which is located in posterior PL. P4 has a complex topographic arrangement. The representation of the vertical meridian is located on the dorsal edge of P4, while the representation of the horizontal meridian divides P4 into dorsal and ventral portions.

Comparative Pulvinar Organization Across Different Primate Species.

In this chapter, we compare the pattern of pulvinar immunohistochemical staining for the calcium-binding proteins calbindin and parvalbumin and for the neurofilament protein SMI-32 in macaque, capuchin, and squirrel monkeys. This group of New and Old World primates shares five similar pulvinar subdivisions: PIP, PIM, PIC, PIL, and PILS. In the Old World macaque monkey, the inferior-lateral pulvinar can be subdivided into the P1 and P2 fields based on its connectivity with visual area V1. On the other hand, only the P1 field and no P2 was found in the New World capuchin monkey. Notably, the similarities in chemoarchitecture contrast with the distinct connectivity patterns and the different visuotopic organizations found across the species.

Response Properties of Pulvinar Neurons Studied with Single-Unit Electrophysiological Recordings.

In this chapter, we discuss the types of visual receptive fields revealed by single-unit electrophysiological recordings in the pulvinar. Nearly all neurons with identifiable receptive fields responded to visual stimulation presented on the contralateral hemifield, within 25° of the fovea. The majority of the visual neurons responded to some form of moving stimulus, and some additionally exhibited direction or orientation selectivity. Most units could be driven by monocular stimulation and showed receptive fields of at least 100 square degrees in area. Finally, most of the units recorded exhibited continuous peripheral receptive fields, even though a few of them could be bilaterally activated.

Modulation of Pulvinar Neuronal Activity by Arousal.

In this chapter, we discuss the modulation of pulvinar neuronal activity by arousal. In contrast to electrophysiological recordings in the early visual cortex, neuronal activity in the pulvinar is particularly sensitive to anesthesia. In the absence of sensory stimulation, pulvinar neurons can be characterized by spontaneous low-frequency rhythmic bursts of spiking activity. However, multisensory stimulation capable of arousing the animal from deeper anesthesia levels is able to reestablish the necessary neuronal dynamics and switch the pulvinar into an active state. Under these conditions, cortical slow-wave activity is substituted by a higher-frequency oscillatory pattern associated with arousal. Here, we describe two types of transitions in pulvinar activity pattern that can be observed when arousing the animal with multisensory stimulation.

GABA Inactivation of the Pulvinar.

In this chapter, we discuss the effects of GABA (gamma-aminobutyric acid) inactivation of the pulvinar on the electrophysiological responses to visual stimuli. A direct way to access the pulvinar-cortical interaction is to pharmacologically inactivate the pulvinar and measure the impact on cortical activity. To this aim, we have focused our efforts on recording in cortical visual area V2 while inactivating the topographically corresponding region of the pulvinar.

The Role of the Pulvinar in Spatial Visual Attention.

This chapter deals with the role of the pulvinar in spatial visual attention. There are at least two aspects in which the pulvinar seems to be instrumental for selective visual processes. The first aspect concerns pulvinar connectivity pattern. The pulvinar is connected with brain regions known to be playing a role in attentional mechanisms, such as area V4, the superior colliculus (SC), and the inferior parietal cortex (IP). Additionally, the pulvinar is richly interconnected with multiple cortical areas. This enables the pulvinar to serve as a hub for brain communication, potentially gating the flow of information across different regions. The second aspect concerns neuronal circuits intrinsic to the pulvinar. We claim these circuits are subserving three basic steps regarding the allocation of spatial attention: disengaging from the current focus of attention, moving it to a new target, and engaging it at a new position.

Precise visuotopic organization of the blind spot representation in primate V1.

The optic disk is a region of the retina consisting mainly of ganglion cell axons and blood vessels, which generates a visual scotoma known as the blind spot (BS). Information present in the surroundings of the BS can be used to complete the missing information. However, the neuronal mechanisms underlying these perceptual phenomena are poorly understood. We investigate the topography of the BS representation (BSR) in cortical area V1 of the capuchin monkey, using single and multiple electrodes. Receptive fields (RFs) of neurons inside the BSR were investigated using two distinct automatic bias-free mapping methods. The first method (local mapping) consisted of randomly flashing small white squares. For the second mapping method (global mapping), we used a single long bar that moved in one of eight directions. The latter stimulus was capable of eliciting neuronal activity inside the BSR, possibly attributable to long-range surround activity taking place outside the borders of the BSR. Importantly, we found that the neuronal activity inside the BSR is organized topographically in a manner similar to that found in other portions of V1. On average, the RFs inside the BS were larger than those outside. However, no differences in orientation or direction tuning were found between the two regions. We propose that area V1 exhibits a continuous functional topographic map, which is not interrupted in the BSR, as expected by the distribution of photoreceptors in the retina. Thus V1 topography is better described as "visuotopic" rather than as a discontinuous "retinotopic" map.

Controversies about the visual areas located at the anterior border of area V2 in primates.

Anatomical and electrophysiological studies have provided us with detailed information regarding the extent and topography of the primary (V1) and secondary (V2) visual areas in primates. The consensus about the V1 and V2 maps, however, is in sharp contrast with controversies regarding the organization of the cortical areas lying immediately rostral to V2. In this review, we address the contentious issue of the extent of the third visual area (V3). Specifically, we will argue for the existence of both ventral (V3v) and dorsal (V3d) segments of V3, which are located, respectively, adjacent to the anterior border of ventral and dorsal V2. V3v and V3d would together constitute a single functional area with a complete representation of both upper and lower visual hemifields. Another contentious issue is the organization of the parietal-occipital (PO) area, which also borders the rostral edge of the medial portion of dorsal V2. Different from V1, V2, and V3, which exhibit a topography based on the defined lines of isoeccentricity and isopolar representation, area PO only has a systematic representation of polar angles, with an emphasis on the peripheral visual field (isoeccentricity lines are not well defined). Based on the connectivity patterns of area PO with distinct cytochrome oxidase modules in V2, we propose a subdivision of the dorsal stream of visual information processing into lateral and medial domains. In this model, area PO constitutes the first processing instance of the dorsal-medial stream, coding for the full-field flow of visual cues during navigation. Finally, we compare our findings with those in other species of Old and New World monkeys and argue that larger animals, such as macaque and capuchin monkeys, have similar organizations of the areas rostral to V2, which is different from that in smaller New World monkeys.

Quantification of early stages of cortical reorganization of the topographic map of V1 following retinal lesions in monkeys.

We quantified the capacity for reorganization of the topographic representation of area V1 in adult monkeys. Bias-free automated mapping methods were used to delineate receptive fields (RFs) of an array of neuronal clusters prior to, and up to 6 h following retinal lesions. Monocular lesions caused a significant reorganization of the topographic map in this area, both inside and outside the cortical lesion projection zone (LPZ). Small flashed stimuli revealed responses up to 0.85 mm inside the boundaries of the LPZ, with RFs representing regions of undamaged retina immediately surrounding the lesion. In contrast, long moving bars that spanned the scotoma resulting from the lesion revealed responsive units up to 1.87 mm inside the LPZ, with RFs representing interpolated responses in this region. This reorganization is present immediately after monocular retinal lesioning. Both stimuli showed a similar and significant (5-fold) increase of the RF scatter in the LPZ, 0.56 mm (median), compared with the undamaged retina, 0.12 mm. Our results reveal an array of preexisting subthreshold functional connections of up to 2 mm in V1, which can be rapidly mobilized independently from the differential qualitative reorganization elicited by each stimulus.

A conserved pattern of differential expansion of cortical areas in simian primates.

The layout of areas in the cerebral cortex of different primates is quite similar, despite significant variations in brain size. However, it is clear that larger brains are not simply scaled up versions of smaller brains: some regions of the cortex are disproportionately large in larger species. It is currently debated whether these expanded areas arise through natural selection pressures for increased cognitive capacity or as a result of the application of a common developmental sequence on different scales. Here, we used computational methods to map and quantify the expansion of the cortex in simian primates of different sizes to investigate whether there is any common pattern of cortical expansion. Surface models of the marmoset, capuchin, and macaque monkey cortex were registered using the software package CARET and the spherical landmark vector difference algorithm. The registration was constrained by the location of identified homologous cortical areas. When comparing marmosets with both capuchins and macaques, we found a high degree of expansion in the temporal parietal junction, the ventrolateral prefrontal cortex, and the dorsal anterior cingulate cortex, all of which are high-level association areas typically involved in complex cognitive and behavioral functions. These expanded maps correlated well with previously published macaque to human registrations, suggesting that there is a general pattern of primate cortical scaling.

Architecture of the inferior parietal cortex in capuchin monkey.

We studied the organization of the inferior parietal cortex (IPC) in five capuchin monkey (6 hemispheres) using cytoarchitectonic (Nissl), myeloarchitectonic (Gallyas), and immune-architectonic (SMI-32 monoclonal antibody) techniques. We partitioned the IPC into five distinct areas: PFG, PG, Opt, PFop, and PGop. Since we used parasagittal sections, we were not able to study area PF due to its far lateral position, which yielded slices that were tangential to the pial surface. Areas PFG, PG, and Opt were in the convexity close to the lateral sulcus, while PFop and PGop were positioned more posteriorly, in the opercular region of IPC. Of all the five regions, area Opt was the one most similar to its analogue in the macaque, especially as revealed with SMI-32 staining. Namely, in both primate species area Opt showed a low density of large pyramidal neurons. Additionally, the apical dendrites of these neurons were sparse and vertically orientated, resembling columns. We also found area PG to be similar: both species exhibited cell body layers with a radial arrangement. On the other hand, Nissl staining revealed area PFG to be architectonically different between New and Old-World monkeys: PFG in the capuchin showed a comparatively higher cell density than in macaques, especially in layers II and IV. These results suggest that evolution may have enabled the functional specialization of these brain regions based on behavioral demands of upper limb use. The small differences in the IPC of the two primates may be linked to interspecies variability.