Classic Columns

Mountcastle (1957) introduced the concept of cortical columns after reporting that recordings along microelectrode trajectories tangential to the surface of somatosensory cortex encountered short sequences of neurons that responded either to light touch on the skin (superficial skin receptors) or touch with pressure (deep receptors). This grouping of cortical neurons according to how they respond to sensory stimuli led to the concept of a patchwork of alternating columns of neurons that extend across all cortical layers, with each type of column activated by a different somatosensory input. The subsequent evidence for such alternating patches of neurons activated by either deep or superficial receptors of the skin and deeper tissue has been limited, and they do not seem to exist in area 3b (S1 proper) of somatosensory cortex of monkeys. Instead, there is evidence for a modular arrangement of groups of neurons in layer 4 that responds to activation by inputs relayed from either slowly adapting or rapidly adapting cutaneous receptors of the skin (Sur et al., 1981, 1984). There is also evidence for at least a partial segregation of territories activated by slowly adapting and rapidly adapting receptors in area 1 of somatosensory cortex of monkeys (Friedman et al., 2004). However, given these limited observations, we can say little about the phyletic distribution of slowly adapting and rapidly adapting cortical columns, or their evolution, even in primates.

More can be said about the blob and interblob surround organization of primary visual cortex (V1) in primates (Fig. 7.2). All primates seem to have a pattern of cytochrome oxidase (CO)-rich blobs (reflecting high metabolic activity) within interblob surrounds of lower CO levels (Horton, 1984; Horton and Hedley-Whyte, 1984; Preuss and Kaas, 1996). Neurons in the blobs respond to color, are less selective for stimulus orientation, and have higher firing rates than neurons between the blobs (Livingstone and Hubel, 1984; Hendrickson, 1985; Felleman, 2008; Lu and Roe, 2008; Economides et al., 2011). However, blobs and interblob regions are found not only in primates with trichromatic or dichromatic color systems but also in nocturnal primates with only one functional type of cone in the retina (Wikler and Rakic, 1990). The blobs and interblobs are also distinguished by different patterns of inputs from the visual thalamus, intrinsic connections, and connections with other visual areas (Livingstone and Hubel, 1984; Casagrande and Kaas, 1994). In macaque monkeys, most of these connections are well developed in newborns (Barone et al., 1996; Baldwin et al., 2012). The segregation of groups of neurons by differences in response characteristics that are mediated by differences in activating inputs fits the classic definition of cortical columns, although the blobs and interblobs do not occupy equal territories, and the interblob territory is continuous. The blob and surround pattern evolved in the immediate ancestors of primates, or in archaic primates, given that none of the close relatives of primates, tree shrews, rodents, and lagomorphs have blobs in V1.

FIGURE 7.2

Anatomically defined columns in visual cortex of primates. Sections of primary visual cortex (V1) and the adjoining second visual area (V2) of a macaque monkey have been cut parallel to the brain surface and processed for CO, a marker of neurons with (more...)

Classic columns are also found in the second visual area, V2, of most primates, where V2 is characterized by a repeating series of CO-dense thick stripes and CO-dense thin stripes separated by CO-pale interstripes. These band-like stripes cross the narrow width of V2, and they seem to exist in all anthropoid primates (Kaas, 2003). The three types of stripes differ in anatomical connections and have neurons with different response properties. The stripes and differences in connections are apparent in newborn macaques (Barone et al., 1996; Baldwin et al., 2012). Although the CO-dense stripes are not consistently distinguishable as thick or thin, they can be identified by functional differences, with neurons in the thick stripes sensitive to binocular disparities and stimulus orientation, the neurons in the thin stripes sensitive to luminance and color, and neurons in pale stripes sensitive to stimulus orientation (Hubel and Livingstone, 1987; Livingstone and Hubel, 1988; Lu and Roe, 2007; Felleman, 2008; Kaskan et al., 2009). The thick stripes project to visual area MT, whereas the other bands project to DL (V4). In prosimian primates, CO stripes in V2 are only weakly apparent, and such stripes are not present in V2 of tree shrews and rodents (Kaas, 2003). Thus, aspects of the stripe pattern may have evolved in early primates, whereas such stripes became fully developed as anthropoid primates emerged.

Although the V1 blob and interblob regions, as well as the V2 stripes, do not look like cylindrical pillars, they otherwise conform to the expectations of classic cortical columns. Other such classic columns undoubtedly exist (Mountcastle, 1997), but they largely remain to be explored. One such example is in the MT crescent, MTc, a visual area that forms a belt around the middle temporal visual area, MT (Fig. 7.1). This poorly understood visual area is composed of a series of CO-dense puffs in a single row, like beads on a string in a belt of CO-pale tissue (Kaas and Morel, 1993). The significance of these puffs and surrounds in MTc, which have different connections with other visual areas, remains to be determined.

Unbounded Columns That Represent Sectors of a Continuous Stimulus Dimension

Several cortical areas have repeating representations of stimulus orientations for different portions of the visual field (Hubel and Wiesel, 1963). Most notably, primary visual cortex of primates, carnivores, and tree shrews have repeating “pinwheel” patterns of cortex, in which stimulus orientation is systematically represented from vertical to horizontal lines and edges and back again (Bonhoeffer and Grinvald, 1991; Fitzpatrick, 1996; Kaschube et al., 2010). Groups of neurons most sensitive to one stimulus orientation or another can be selectively activated, the activity pattern optically imaged, and regions of cortex sensitive to different orientations color coded to produce colorful illustrations of arrays of orientation “columns.” These “columns” differ from classic columns in that they have no borders because the orientations of stimuli change continuously without disruption. Thus, the illustrated “borders” between orientation columns are arbitrary. In addition, all “orientation columns” are selective for the same stimulus features, and thus these columns are not of the classic type, which are segregated by different classes of activating inputs. However, each entire array of orientation-selective neurons, the pinwheel for a given location in the visual field, can be considered as a larger domain or hypercolumn (Hubel and Wiesel, 1972, 1977). Orientation hypercolumns are widespread in visual cortex of primates: they also have been identified in V2 stripes, V3, V4 (DL), and MT (Kaskan et al., 2009, 2010; Tanigawa et al., 2010). Neurons in orientation-selective hypercolumns may be divided for each orientation column into halves, preferring one or the other direction of motion perpendicular to the preferred orientation (Kaskan et al., 2010). The grouping of neurons by their preferences for stimulus orientation seems to be a trait that emerged first in V1 in the common ancestors of tree shrews and primates, because tree shrews also have orientation hypercolumns. However, the more distant relatives, rodents and rabbits, have orientation-selective neurons in visual cortex but not orientation-selective columns (Kaschube et al., 2010). Carnivores have independently evolved orientation hypercolumns in V1. Possibly, the presence of orientation hypercolumns in V1 is a prerequisite for the evolution of such hypercolumns in other visual areas, as found in primates. Orientation hypercolumns have not been reported for areas of extrastriate cortex of tree shrews. Thus, the extrastriate hypercolumns for stimulus orientation may have emerged with the first primates.

Other proposed modules of V2 in primates include subregions of thin stripes selective for different hues (Xiao et al., 2003; Roe, 2004). These hue-selective subregions are not classic columns because they are not separated by columns that are most sensitive to another stimulus feature, and they have arbitrary boundaries.

There is only limited evidence for the existence of classic columns in auditory cortex. All mammals seem to have primary cortical auditory areas that represent the receptors of the cochlea in a linear manner so that neurons are arranged in one dimension across a cortical area from being most sensitive to low-frequency sounds on one end, to high-frequency sounds on the other (Kaas, 2011). Thus, there are no modular divisions based on sound frequency, although isofrequency bands with arbitrary borders have been described. However, bands of primary auditory cortex where neurons that are excited from both ears (EE bands) alternate with bands of cortex with neurons that are excited by the contralateral ear and inhibited by the ipsilateral ear (EI bands) have been reported for cats (Merzenich and Kaas, 1980). The EE and EI bands extend across the isofrequency contours. Because EE and EI bands have neurons of differing functional properties, they qualify as classic columns (although shaped like bands). Such bands have not been identified in auditory cortex of primates.

Modules Representing Separated Parts of Sensory Surfaces

Another type of module, one that also would not qualify as a classic column, concerns separations of groups of neurons in somatotopic maps of the body surface, or retinotopic maps of the two eyes, in areas of cortex. The best-known example is the rows and columns of “barrels” in primary somatosensory cortex of rats and mice, where a barrel-like structure represents each of the large sensory whiskers on the side of the face (Woolsey et al., 1975). The digits and pads of the feet also relate to separated groups of neurons (Dawson and Killackey, 1987).

The many studies of the “barrel field” of mice and rats have revealed that differences in neural activity are important in the formation of barrels, such that the number of barrels varies with the number of facial whiskers. Molecular factors also alter the formation of barrels, as revealed in mutant mice (Erzurumlu and Kind, 2001). Such segregations of cortical neurons by body part are found in primary somatosensory cortex of many species, but are perhaps most apparent in the somatosensory cortex of the star-nosed mole, where the highly innervated tactile rays of the nose are each separately represented in three areas of somatosensory cortex (Catania and Kaas, 1996). In primary somatosensory cortex of New World and Old World monkeys (Jain et al., 1998; Qi and Kaas, 2004), and possibly other anthropoid primates, the representations of the digits are separated from each other by narrow cell-poor septa, with a more conspicuous septum separating the representation of digit 1 (thumb) from that of the face. Such separated representations of digits in area 3b of primates are variable and have not been described in prosimian primates. Septa that separate representations of digits are more apparent in macaque monkeys than in New World owl monkeys and squirrel monkeys.

It could be argued that the narrow septal regions that separate the cortical barrels, bands, and other modules related to body parts do have neurons that differ in connections, such as having corpus callosum connections, and thus there is an alteration of functional types of columns in the classical sense. However, the septa are cell-poor, narrow regions that are primarily there to reflect disruptions of the receptor sheet. Yet, these narrow septa may be opportunistically occupied by late-developing sources of input. Because the septa that form module borders reflect junctions in neuron activity patterns during sensory activation, these septa are most apparent early in sensory hierarchies where short response latencies to sensory stimuli are maintained.

The retina of each eye is a continuous sensory surface, except for the nerve head and a narrow septum corresponding to the nerve head, which disrupts layers of the lateral geniculate nucleus that receive projections from the contralateral eye (Kaas et al., 1973). In cortex, the ocular dominance “columns” in primary visual cortex of primates fall into the category of modules based on disruptions of the sensory surface, because the retina of the two eyes have independent activity patterns prenatally. Thus, the afferents from the hemiretina of each eye terminate in separate layers in the lateral geniculate nucleus of the visual thalamus, and then these layers project in retinotopically matched patterns to primary visual cortex to either congruently overlap or to separate locally in variable patchy-to-banding patterns in layer IV while maintaining some level of retinotopy, depending on species (Florence and Kaas, 1992; Horton and Adams, 2005). Ocular dominance columns, first revealed in microelectrode recordings (Hubel and Wiesel, 1968), and axon termination patterns from layers of the lateral geniculate nucleus (Wiesel et al., 1974) can also be demonstrated by differences in activity levels after blocking activity from one eye (Horton, 1984; Takahata et al., 2009a). The segregation of eye-related afferents is very weak in some primates, such as nocturnal prosimian galagos and owl monkeys (Kaskan et al., 2007; Takahata et al., 2011), and highly variable patterns exist in New World monkeys, even across individuals within a species (Horton and Adams, 2005). Ocular dominance patterns may reflect a high degree of segregation of thalamic afferents in layer 4 of primary visual cortex, as in Old World monkeys (Fig. 7.3), apes, and humans, or reflect such a low level of separation that they are anatomically cryptic and only revealed by relative differences in neural responses to each eye as revealed in optical imaging experiments (Kaskan et al., 2007) or the expression pattern of activity-dependent genes (Takahata et al., 2009b). Ocular dominance “columns” are absent in the closest relatives of primates, tree shrews, rodents, and rabbits, and thus are a feature of visual cortex that evolved in early primates but became more pronounced in Old World monkeys, apes, and humans. Obvious ocular dominance columns have evolved independently in carnivores (Anderson et al., 1988), and they likely exist in other taxa.

FIGURE 7.3

Ocular dominance columns (bands) in a flat surface view of primary visual cortex (V1) of an Old World macaque monkey as reflected by distribution of terminations of lateral geniculate axons related to each eye in cortical layer 4. Regions of black receive (more...)

Domains: Larger Functional Divisions of Cortical Areas

Primary motor cortex and dorsal and ventral premotor areas are widely recognized as valid cortical areas, and each of these areas has a somatotopic representation of small movements of body parts that are revealed by brief trains of near-threshold pulses of electrical current. However, cortical motor areas representing major body parts, such as the forelimb, have a locally fractured somatotopy so that different movement zones, roughly the size of minicolumns, are mixed and repeated (Fig. 7.4). Thus, the forelimb region mixes zones for digit, wrist, elbow, and shoulder movements in a puzzling arrangement (Gould, 1986; Donoghue et al., 1992; Qi et al., 2000) that is unlike that of primary sensory representations, which closely reflect the organization of the sensory sheet. However, the somatosensory representation of tactile projections to the cerebellar cortex forms a fractured representation of the body surface (Shambes et al., 1978), much like the representations in motor cortex. The explanation for these adjoining patches of cerebellar cortex devoted to various nonadjacent body parts was that neurons in groups of such patches could interact to form “action-involved structures” for directing movement patterns.

FIGURE 7.4

Proposed functional organization of the hand–forearm segment of primary motor cortex (M1) in monkeys and other primates. Although M1 has an overall somatotopy, the local somatotopy is fractured to form a mosaic of radial rows of neurons that evoke (more...)

It has long been known that longer trains of electrical pulses at higher current levels evoke more complex movement sequences from motor cortex than do short trains at threshold levels (Leyton and Sherrington, 1917). More recently, Graziano et al. (2002) have used longer (0.5 s) trains of electrical pulses to define different regions or domains (Fig. 7.1) in motor cortex where different ethologically relevant movement can be evoked (climbing, reaching, grasping, defense of the head, hand-to-mouth). Matching movement domains have been identified in posterior parietal cortex (Cooke et al., 2003; Stepniewska et al., 2005; Gharbawie et al., 2011a,b). In primary motor cortex, several different domains for functionally distinct movement patterns are found in separate parts of the forelimb representation, perhaps offering some explanation for the mosaic of minicolumns for different but related small movements and muscle twitches that are revealed by short trains of pulses at threshold levels of stimulating current (Fig. 7.4). Thus, circuits within a domain may evoke sequences of movements involving the different body parts represented within the domain.

Functionally matched domains for at least some of the complex movement patterns of primary motor cortex also exist in premotor cortex and in posterior parietal cortex. The domains in posterior parietal cortex may be parts of larger cortical areas. The domains in frontal and posterior parietal cortex have similar spatial arrangements in prosimian galagos, two species of New World monkeys, and Old World macaque monkeys, and there is indirect evidence for them in humans (Kaas et al., 2011). Thus, they likely exist in all primates. Such domains for complex movements may also exist in motor cortex of the relatives of primates, tree shrews and rodents, where M1 also has a fractured somatotopy (Remple et al., 2007; Cooke et al., 2011). However, posterior parietal cortex is no more than a narrow strip of cortex in tree shrews and rodents and is unlikely to contain a series of primate-like domains.

Other areas of cortex may also have larger functionally distinct regions within cortical areas. For example, some of the face-selective and object-selective regions of temporal cortex in macaque monkeys and humans resemble domains (Tsao et al., 2003, 2008a; Pinsk et al., 2005; Rajimehr et al., 2009). Likewise, the large visual area termed V4 or DL has been divided into large regions or domains of neurons that are either color selective or orientation selective (Tanigawa et al., 2010), although these large regions might also be considered separate cortical areas (Cusick and Kaas, 1988; Stepniewska and Kaas, 1996).

How Do Columns and Modules Emerge in Development?

A number of factors likely contribute to the functional organization of cortex, but at the modular level, activity-dependent selection of coactive afferents together with cellular signals that are position dependent probably are two of the most important variables (Erzurumlu and Kind, 2001; Sur and Leamey, 2001; Kaas and Catania, 2002). There is considerable evidence to support this conclusion, but some of the most impressive evidence comes from studies that created three-eyed frogs (Constantine-Paton and Law, 1978; Katz and Constantine-Paton, 1988). In frogs, each optic tectum normally receives inputs from only the contralateral eye, but when a third eye is added experimentally to one side of the head during embryonic development, both eyes on that side compete for territory in the same contralateral optic tectum. The projections from each of these eyes respond to molecular signals that tend to produce the same retinotopic pattern in the optic tectum, but local groups of tectal neurons favor inputs from one eye or the other. The result is that the afferents from the two eyes form alternating bands or stripes that resemble the ocular dominance bands in cats and anthropoid primates. The borders between these bands in the optic tectum and visual cortex correspond to locations where abrupt differences in activity patterns occur, and they do not develop or they degrade when activity is blocked (Cline et al., 1987). Obviously, the ability to form ocular dominance bands did not evolve via natural selection in the optic tectum of frogs for some future function. Instead, the developmental factors that produced these columns were present for other reasons that are not clear but apparently are widely important in nervous system development (Katz and Constantine-Paton, 1988). The capacity for module formation seems to be inherent in all cortical tissue, as well as in other tissue such as the optic tectum or superior colliculus, where inputs of different activation patterns compete for location with an overall global map. Thus, ocular dominance bands and other configurations, as well as orientation modules and other types of columns, including those based on discontinuities of the receptor sheet, have emerged independently in several lines of mammalian evolution. For some of these types of modules, asking what they do (Horton and Adams, 2005) may be the wrong question. Instead, we might ask, what else is achieved in neural tissue by the mix of activity-dependent and position-dependent factors that select and group synaptic contacts when these factors coexist at particular developmental times? Purves et al. (1992) have suggested that some of the columns that have been described in cortex are “by-products” of synaptic development. If so, what is the product?