Abstract

Neocortical pyramidal cells are characterized by markedly different structure among cortical areas in the mature brain. In the ventral visual pathway of adult primates, pyramidal cells become increasingly more branched and more spinous with anterior progression through the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. It is not known how these regional specializations in neuron structure develop. Here, we report that the basal dendritic trees of layer III pyramidal cells in V1, V2, V4, TEO, and TE were characterized by unique growth profiles. Different numbers of spines were grown in the dendritic trees of cells among these cortical areas and then subsequently pruned. In V1, V2, and V4, more spines were pruned than grew resulting in a net decrease in the number of spines in the dendritic trees following the onset of visual experience. In TEO and TE, neurons grew more spines than they pruned from visual onset to adulthood. These data suggest that visual experience may influence neuronal maturation in different ways in different cortical areas.

Introduction

Pyramidal cell structure varies dramatically among cortical areas in the adult primate brain. Estimates of the total number of spines (putative excitatory inputs) in the dendritic trees of pyramidal cells reveal more than a 30-fold difference between populations of cells sampled in different cortical areas (Elston et al. 2006). There are systematic trends for increasingly more complex dendritic trees through series of functionally related cortical areas. For example, neurons become progressively larger, more branched, and more spinous with anterior progression through the dorsal and ventral visual pathways (Elston and Rosa 1997, 1998, 2000; Elston et al. 1999a, 1999b; Elston 2003c; Elston, Benavides-Piccione, Elston, DeFelipe, and Manger 2005a; Elston, Benavides-Piccione, Elston, Manger, and DeFelipe 2005a; Elston, Elston, Casagrande, and Kaas 2005b; Elston, Elston, Kaas, and Casagrande 2005). Similarly, there is a progressive systematic increase in complexity of pyramidal cell structure through somatosensory areas 3b, 1, 2, 5, and 7 (Elston and Rockland 2002; Elston, Benavides-Piccione, Elston, DeFelipe, and Manger 2005b; Elston, Benavides-Piccione, Elston, Manger, and DeFelipe 2005b) and with anterior progression through cingulate areas 23 and 24 to dorsolateral granular prefrontal cortex (Elston 2000; Jacobs et al. 2001; Elston, Benavides-Piccione, and DeFelipe 2005; Elston, Benavides-Piccione, Elston, DeFelipe, and Manger 2005c; Elston, Benavides-Piccione, Elston, Manger, and DeFelipe 2005c; Elston, Elston, Casagrande, and Kaas 2005a; Anderson et al. 2009).

These specializations in pyramidal cell structure are likely to influence cortical function at the systems, cellular and subcellular levels (Jacobs and Scheibel 2002; Elston 2003b; Treves 2005; Spruston 2008). Specifically, the complexity of their dendritic structure influences their biophysical properties, their functional capacity, and potential for plastic change (Koch 1999; Mel 1999; Jan YN and Jan LY 2001; Chklovskii et al. 2004; London and Häusser 2005). Differences in the number of spines in the dendritic trees, each of which receives asymmetrical excitatory synapse (DeFelipe et al. 1988; Petralia, Wang, Wenthold 1994a, 1994b; Petralia, Yokotani, Wenthold 1994; Arellano et al. 2007), reflect different numbers of inputs integrated by individual neurons and the complexity of patterns of connectivity. Indeed, there is a parallel in the complexity of pyramidal cell dendritic trees and various aspects of their physiological properties. For example, the increase in the size of the dendritic trees (in the tangential plane) parallels an increase in the receptive field size of neurons through the ventral pathway areas, the primary (V1), second (V2), and fourth (V4) visual areas, and cytoarchitectonic areas TEO and TE of the inferior temporal cortex (for reviews, see Elston 2002; Fujita 2002).

It remains to be determined how pyramidal cells come to be so specialized in different cortical areas. There are 2 opposing views in the literature regarding how cortical areas develop. One view posits that all cortical areas mature at the same rate (Bourgeois and Rakic 1993; Bourgeois et al. 1994), whereas the other view states that different cortical areas mature at different rates (Huttenlocher and Dabholkar 1997; Travis et al. 2005; Petanjek et al. 2008). Recently, we demonstrated that layer III pyramidal cells in V1, TE, and the granular prefrontal cortex of the macaque monkey grow, and subsequently prune, markedly different numbers of dendritic spines during normal development (Elston et al. 2009). Different numbers of spines are grown in the dendritic trees of these cells prior to birth. However, little is known about relative developmental profiles of pyramidal cells among cortical areas associated with functional hierarchies such as those proposed in visual cortex (Maunsell and Newsome 1987; Felleman and Van Essen 1991). Here, we performed a systematic study in which we quantified the structure of layer III pyramidal cells in cortical areas of the ventral visual pathway of the macaque monkey from birth to adulthood. Our findings reveal similarities and differences in the developmental profiles of pyramidal cells among cortical areas. In particular, we reveal 2 opposing postnatal developmental trends: dendritic atrophy and net spine loss in V1, V2, and V4 and dendritic growth and net spinogenesis in TEO and TE.

Materials and Methods

Eight male cynomolgus monkeys (Macaca fascicularis) were used in the present study (Table 1). The cell injection methodology and immunohistochemical processing employed in the present study have been outlined in detail in previous studies (Buhl and Schlote 1987; Elston and Rosa 1997; Elston 2001). The animals were deeply anesthetized with sodium pentobarbital (Nembutal, >75 mg/kg intravenously or intraperitoneally; Dainippon Sumitomo Pharma, Osaka, Japan) in accordance with protocols approved by Osaka University and regulations for the care and use of animals set out by the National Institutes of Health (publication No. 86-23, revised 1996) and perfused intracardially, and the brain was removed.

Table 1

Vital data of the animals used in the present study

Age Animal Gender Body weight (kg) Hemisphere 
2D CI9 Male 0.35 Right 
3W CI1 Male 0.56 Right 
3½M CI10 Male 0.56 Right 
7M CI8 Male 0.70 Right 
14M AM1 Male 1.3 Right 
23M SM1 Male 1.5 Right 
4½Y MF1 Male N/A Right 
4½Y CI12 Male 2.7 Right 
Age Animal Gender Body weight (kg) Hemisphere 
2D CI9 Male 0.35 Right 
3W CI1 Male 0.56 Right 
3½M CI10 Male 0.56 Right 
7M CI8 Male 0.70 Right 
14M AM1 Male 1.3 Right 
23M SM1 Male 1.5 Right 
4½Y MF1 Male N/A Right 
4½Y CI12 Male 2.7 Right 

Note: 14M, 14 months of age; 23M, 23 months of age; N/A, not available.

Tissue was taken from the exposed portion of the occipital lobe (V1; corresponding approximately to the central 5–7 degrees of the visual representation) (Daniel and Whitteridge 1961), the posterior bank of the inferior occipital sulcus (V2; corresponding approximately to the central 1–2 degrees) (Gattass et al. 1981; Levitt, Kiper, and Movshon 1994; Roe and T'so 1995), the middle third of the prelunate gyrus (V4; corresponding approximately to 10–20 degrees in the visual representation) (Gattass et al. 1988), the dorsolateral portion of the occipitotemporal transition (TEO), and the middle third of the inferior temporal gyrus immediately anterior to the posterior middle temporal sulcus (TE, TEp of Seltzer and Pandya 1978, TEpd of Yukie 1997) (Fig. 1). All tissue blocks were sampled from the right hemisphere. The white matter was trimmed from the blocks, and the remaining gray matter was “unfolded” and postfixed overnight between glass slides in a solution of 4% paraformaldehyde in 0.1 M phosphate buffer (PB).

Figure 1.

Schematic illustrating where neurons were sampled (dots) in the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. The lateral view of the cerebral cortex is shown with the lunate sulcus (ls) and the inferior occipital sulcus (ios) opened and with a visuotopic map adapted from Gattass et al. (1981, 1988). pmts: posterior middle temporal sulcus.

Figure 1.

Schematic illustrating where neurons were sampled (dots) in the primary (V1), second (V2), and fourth (V4) visual areas and cytoarchitectonic areas TEO and TE. The lateral view of the cerebral cortex is shown with the lunate sulcus (ls) and the inferior occipital sulcus (ios) opened and with a visuotopic map adapted from Gattass et al. (1981, 1988). pmts: posterior middle temporal sulcus.

Serial thick sections (250 μm) were cut tangential to the cortical surface with the aid of a vibratome (Vibratome series 1000). Individual sections were incubated in a solution containing 10−5 M of the fluorescent dye 4,6-diamidino-2-phenylindole (DAPI; Sigma D9542, St Louis, MO) in PB at room temperature for 5–10 min and mounted between Millipore filters (AABG02500, Billerica, MA). The slice preparation was then mounted in a perspex dish on a fixed-stage microscope (Eclipse FN1; Nikon, Tokyo, Japan) and the preparation visualized with UV excitation (380–420 nm).

In the present study, we focused on pyramidal cells at the base of layer III. For reasons outlined elsewhere (Casagrande and Kaas 1994; Elston and Rosa 1998), we use the nomenclature of Hassler (1966) for the cortical layer, thus avoiding confusion when comparing aspects of cortical microcircuitry among primate species and among cortical areas (e.g., Elston et al. 2006; Sherwood et al. 2007). Layer III was easily identified in the DAPI-labeled sections immediately above the neuron-dense granular layer. Even in tangential sections, it is easy to distinguish the transition from layer III to layer IV due to the change in density and size of somata (see Fig. 3 of Elston and Rosa 1997).

DAPI-labeled neurons were injected with Lucifer Yellow (Lucifer Yellow CH dilithium salt, L-0259, Sigma; dissolved in 0.05 M Tris buffer, pH = 8.4) under visual guidance with continuous current (up to 100 nA). Neurons were injected in tangential sections so as to be able to reconstruct the entire basal dendritic tree. By injecting neurons in the tangential plane, aspects of their structure can be related directly with features reported elsewhere such as intrinsic axon patches (Yoshioka et al. 1992; Lund et al. 1993; Levitt, Kiper, and Movshon 1994, Levitt, Yoshioka, and Lund 1994; Fujita I and Fujita T 1996) and receptive fields (Daniel and Whitteridge 1961; Gattass et al. 1981, 1988; Movshon et al. 1999). Such an approach has been central to the demonstration of regional and species specializations in pyramidal cell structure as the entire tangential extent of the basal dendritic tree is revealed, unlike in most previous studies in transverse sections in which many of the basal dendrites are truncated. Such studies in “thin” transverse sections bias for uniformity and mask the sort of differences in neuronal morphology detectable in tangential sections.

Once a suitable number of neurons had been injected, the slice was processed for a light-stable reaction product (Elston and Rosa 1997). The sections were processed in a solution containing 0.6 μg/mL biotinylated anti–Lucifer Yellow (A-5751; Invitrogen, Carlsbad, CA) in stock solution (2% bovine serum albumin [A3425; Sigma], 1% Triton X-100 [X100; Sigma–Aldrich], 0.1% sodium azide, and 5% sucrose in PB) for 4–11 days at room temperature, washed 3 times for 10 min each in PB, incubated in streptavidin-biotinylated horseradish peroxidase complex (1:100; RPN1051, GE Healthcare, Uppsala, Sweden) for 2 h, washed 3 times for 10 min each in PB, then incubated in 0.5% 3,3′-diaminobenzidine tetrahydrochloride (DAB, D5637, Sigma; 1:200 in PB) for 10 min at room temperature before being reacted in a solution containing 1% hydrogen peroxide and 0.5% DAB in PB. This method yields a light-stable robust reaction product (Fig. 2).

Figure 2.

Photomicrographs of layer III pyramidal cells injected in tangential sections sampled from areas V1 (AD) and TE (EH). Cells were injected individually with lucifer yellow, and then the section was processed for standard immunohistochemical techniques to reveal a robust, light-stable DAB reaction product. Individual dendritic spines are easily visible at higher magnification (BD and FH), revealing differences in spine density according to age. Note in V1 there is a visible increase in spine density from 2 days old (B) to 3½M (C) and a visible decrease in spine density by 4½Y (D). In area TE, there was a visible increase in spine density from 2 days old (F) to 3½M (G) but, unlike in V1, there was not a dramatic decrease in spine density by 4½Y (H). Scale bars = 10 μm.

Figure 2.

Photomicrographs of layer III pyramidal cells injected in tangential sections sampled from areas V1 (AD) and TE (EH). Cells were injected individually with lucifer yellow, and then the section was processed for standard immunohistochemical techniques to reveal a robust, light-stable DAB reaction product. Individual dendritic spines are easily visible at higher magnification (BD and FH), revealing differences in spine density according to age. Note in V1 there is a visible increase in spine density from 2 days old (B) to 3½M (C) and a visible decrease in spine density by 4½Y (D). In area TE, there was a visible increase in spine density from 2 days old (F) to 3½M (G) but, unlike in V1, there was not a dramatic decrease in spine density by 4½Y (H). Scale bars = 10 μm.

Cells were included for analysis only if they had an unambiguous apical dendrite, had their complete basal dendritic arbors contained within the section, and were well filled. Neurons were reconstructed with the aid of Neurolucida system (MBF Bioscience, Williston, VT) coupled with a microscope (Eclipse 80i; Nikon) equipped with a motorized stage (Ludl, Hawthorne, NY) and a CCD camera (CX9000; MBF Biosciences). The size of the dendritic trees was determined in the tangential plane as the area contained within a convex hull traced around the outermost distal dendritic terminations in reconstructions collapsed into 2 dimensions (Fig. 3 inset). The branching structure of the dendritic trees was determined by Sholl analyses (Sholl 1955) centered on the cell body in reconstructions collapsed into 2 dimensions (Fig. 4 inset).

Figure 3.

Frequency histograms of the size of the basal dendritic trees of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Arrowheads indicate the means.

Figure 3.

Frequency histograms of the size of the basal dendritic trees of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Arrowheads indicate the means.

Figure 4.

Sholl plots of the branching patterns of the basal dendritic trees of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Arrowheads and dashed lines indicate the location of the peak branching complexity. Shades indicate the standard deviations.

Figure 4.

Sholl plots of the branching patterns of the basal dendritic trees of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Arrowheads and dashed lines indicate the location of the peak branching complexity. Shades indicate the standard deviations.

Spine densities were calculated by drawing horizontally projecting dendrites, in their entirety, of randomly selected cells with the aid of a Nikon ×100 oil immersion objective (numerical aperture = 1.40) and counting the number of spines per 10-μm segment (Eayrs and Goodhead 1959; Valverde 1967). Horizontally projecting dendrites were selected to avoid trigonometric error. All spines were drawn, and no distinction was made between different spine types (e.g., sessile and pedunculated spines). No correction factors were applied to our estimates of spine densities as 1) the DAB reaction product is less opaque than, for example, the Golgi precipitate allowing visualization of spines that issue from the underside of dendrites, 2) basal dendrites have a diameter smaller than the neck length of most spines, and 3) any possible error that may arise because some populations of cells have thicker basal dendrites than others would only reduce the extent of differences we report for cells among cortical areas (i.e., more spinous cells have, on average, thicker dendrites than the less spinous cells).

Estimates of the total number of spines found within the basal dendritic tree of the “average” cell in each cortical area were made by summing the product of the average number of dendrites by the average spine density for corresponding segments along the dendrites (Elston 2001).

Statistical analyses were performed with the aid of MatLab software (Mathworks, Natick, MA). For tests of the size of the dendritic trees and somata, each cell was represented by a single data point. For Sholl analyses and spine density, multiple data points were sampled for each neuron. These multiple data points were treated as repeated measures according to their spatial location (e.g., measure 1 for the number of branch points at 25 μm from the cell body, measure 2 for the number of branch points at 50 μm from the cell body, and measure 3 for the number of branch points at 75 μm from the cell body or measure 1 for the spine density between 0 and 10 μm from the cell body, measure 2 for the spine density between 10 and 20 μm from the cell body, and measure 3 for the spine density between 20 and 30 μm from the cell body), and the data were tested by repeated measures analyses of variance (ANOVAs). Statistical tests used here are the same as those used in our previous studies.

Results

A total of 955 pyramidal cells in layer III were included for analyses (Table 2). Over 130 000 individual dendritic spines were drawn and tallied. Data are reported as in previous studies of pyramidal cells in the adult brain (Elston and Rosa 1998; Elston et al. 1999a) to allow direct comparison of cell structure in the developing and adult visual cortex of the macaque monkey.

Table 2

Number of layer III pyramidal cells included for study in visual areas of the different animals

 Animal V1a V2 V4 TEO TEa 
2D CI9 25 62 37 36 23 
3W CI1 41 27 25 29 38 
3½M CI10 29 23 32 30 27 
7M CI8 34 43 38 40 52 
14M AM1 — 82 — 43 — 
23M SM1 — — 36 — — 
4½Y MF1 22 — — — 31 
4½Y CI12 37 13 — — — 
 Animal V1a V2 V4 TEO TEa 
2D CI9 25 62 37 36 23 
3W CI1 41 27 25 29 38 
3½M CI10 29 23 32 30 27 
7M CI8 34 43 38 40 52 
14M AM1 — 82 — 43 — 
23M SM1 — — 36 — — 
4½Y MF1 22 — — — 31 
4½Y CI12 37 13 — — — 

Note: 14M, 14 months of age; 23M, 23 months of age.

a

Data for V1 (except for those from CI12) and TE are shared with a previous study (Elston et al. 2009).

Basal Dendritic Field Areas

Pyramidal cells in V1, V2, V4, TEO, and TE differed in their growth profiles from postnatal day 2 (2D) to adulthood (Fig. 3). The dendritic trees of pyramidal cells in V1 were their largest at 2D and continued to diminish in size through 3 weeks of age (3W) to 3½ months of age (3½M), being 27% and 41% smaller than those at 2D, respectively. These cells then appeared to undergo a growth phase from 3½M to 7 months of age (7M) before achieving their adult size. Even in the adult, the dendritic trees of pyramidal cells in V1 were smaller by 34% than those observed at 2D. Cells in V2 and V4 were largest at 3½M, being 78% and 48% larger than those at 2D, respectively. Beyond 3½M, the dendritic trees of cells in V2 and V4 diminished to their adult size, being approximately the same size as observed at 2D. Cells in TEO and TE were largest in the adult brain, being approximately twice the size of those observed at 2D. Statistical analysis (one-way ANOVAs) revealed that the differences in the size of the basal dendritic trees of pyramidal cells in any given cortical area were significant (P < 0.05) across the age groups (V1, F4 = 19.43; V2, F4 = 67.00; V4, F4 = 49.20; TEO, F4 = 140.41; TE, F4 = 100.06).

Because of the different profiles observed in the size of the dendritic trees of cells in each cortical area, there were relative differences in the size of cells among cortical areas for any given age (Fig. 3). For example, at 2D, cells in V1 had larger dendritic trees than those in V2, TEO, and TE. By 3W, cells in V1 were smaller than those in other cortical areas, a pattern observed through to adulthood. At 3½M, cells in V4 and TEO had larger dendritic trees than those in area TE, whereas cells in TE are the largest in the adult brain. Statistical analysis (one-way ANOVAs) revealed that the size of the dendritic trees of cells at any given age was significantly different (P < 0.05) among cortical areas in all animals (2D, F4 = 37.23; 3W, F4 = 32.00; 3½M, F4 = 112.28; 7M, F4 = 137.44; adult [AD], F4 = 311.12).

Branching Patterns of the Basal Dendritic Trees

For any given cortical area, we found changes in the branching complexity, as evidenced by their Sholl profiles, with aging (Fig. 4). In V1, the peak branching complexity (defined as the maximum number of dendritic intersections with the Sholl annuli) occurred at 3W. The same was observed in V2 and TEO. In V4, however, the peak branching complexity occurred at 3½M. In TE, the peak branching complexity occurred at 7M. In addition, we found that the peak branching complexity within the dendritic trees of cells in a given cortical area may change in spatial distribution with aging. For example, in V1, the peak branching complexity was located 75 μm from the cell body at 2D but at 50 μm from the cell body at 3W, 3½M, and 7M. In V4, the peak branching complexity was located 50 μm from the cell body at 2D and 3W but at 75 μm from the cell body at 3½ and 7M. Statistical analysis (1-way repeated measures ANOVA) revealed that the number of dendritic intersections with Sholl annuli within any given cortical area was significant (P < 0.05) across the age groups (V1, F4 = 4.97; V2, F4 = 5.38; V4, F4 = 11.21; TEO, F4 = 3.71; TE, F4 = 13.58). Comparison of the branching complexity in the dendritic trees of pyramidal cells among cortical areas at each given age revealed that cells in V1 and V2 have fewer branches than those in TEO and TE at all corresponding ages (Fig. 4; P < 0.05, Mann–Whitney U-test). Statistical analysis (one-way repeated measures ANOVA) revealed that the number of dendritic intersections with Sholl annuli was significantly different among cortical areas (P < 0.05) at each given age (2D, F4 = 13.00; 3W, F4 = 11.48; 3½M, F4 = 33.07; 7M, F4 = 45.77; A, F4 = 51.20).

Spine Densities of the Basal Dendrites

In all cortical areas, we found a trend for increasing spine density from 2D through 3W to 3½M (Fig. 5; see also Fig. 2 for microphotographs). This increase was evident along the entire extent of the dendrites, with the exception of the proximal region, which is devoid of spines. By 7M, there had been a considerable decrease in spine density in the dendritic trees of cells in all cortical areas. Again, for any given cortical area, this decrease in spine density was relatively uniform along the entire extent of the dendrite (with the exception of the proximal segments). There were, however, notable differences in the rate of increase/decrease in spine density, as well as the peak spine density (the highest value observed along the entire extent of the dendrites), among cortical areas at the different age groups. For example, although cells in V1 have a lower spine density profile than those in V2 at 2D, the rate of increase in spine density in V1 with aging exceeds that in V2 such that by 3½M cells in V1 have markedly higher spine density than those in V2. A similar trend was observed between V1 and V4. The highest rates of increase in spine density were observed in TEO and TE. Spine density in area TEO increased by 2-fold at comparable distances along the dendrites from 3W to 3½M. Repeated measures ANOVAs revealed these differences in spine density in each cortical area to be significantly different (P < 0.05; V1, F4 = 417.4; V2, F4 = 441.9; V4, F4 = 609.5; TEO, F4 = 594.5; TE, F4 = 300.1). Repeated measures ANOVAs also revealed significant differences (P < 0.05) in spine density among cortical areas for each given age group (2D, F4 = 243.2; 3W, F4 = 456.1; 3½M, F4 = 287.4; 7M, F4 = 375.5; A, F4 = 169.7).

Figure 5.

Profiles of the spine density of the basal dendrites of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Note that scales in the ordinate are different for the different areas. Shades indicate the standard deviations.

Figure 5.

Profiles of the spine density of the basal dendrites of layer III pyramidal neurons sampled from V1, V2, V4, TEO, and TE. Note that scales in the ordinate are different for the different areas. Shades indicate the standard deviations.

By combining data from the Sholl analyses with that of spine densities, we were able to calculate an estimate for the total number of dendritic spines in the basal dendritic tree of the “average” pyramidal neuron in each area for the different age groups (Elston 2001). These calculations revealed dramatic differences in spinogenesis and pruning in the dendritic trees of cells in visual cortex (Fig. 6). Cells in V1 had approximately 1900 spines in their dendritic trees at 2D; this number increased to a maximum of approximately 3800 at 3½M and subsequently decreased to approximately 900 in the adult. Cells in V2 had an estimated 2800 spines in their dendritic trees at 2D, increasing to a maximum of nearly 5000 at 3½M before declining to 1100 in the young adult. Cells in V4 were the most spinous of all cells at 2D (approximately 9000). Interestingly, cells in V4 then appeared to prune spines in the following weeks before undergoing considerable spinogenesis to reach a maximum of >9000 spines at 3½M. Thereafter, spines were pruned to reach 2400 spines in the adult. Cells in TEO had 3600 spines at 2D, increasing to 14 100 spines at 3½M before decreasing to 4800 spines in the young adult. Cells in TE had 3100 spines at 2D, increasing to nearly 10 400 spines at 3½M before decreasing to 6200 spines in the adult. In V1, V2, and V4, cells in the adult are considerably less spiny than those at 2D, meaning that more spines were pruned from the dendritic trees of these cells than are grown. In TEO and TE, on the other hand, cells in the adult are considerably more spiny than those at 2D. Thus, in inferior temporal cortex spine growth is greater than spine loss, resulting in a net increase in spine number.

Figure 6.

Graph of the total number of spines in the basal dendritic tree of the “average” layer III pyramidal cell in V1, V2, V4, TEO, and TE at 2D, 3W, 3½M, 7M, and adults (AD). Error bars = standard errors.

Figure 6.

Graph of the total number of spines in the basal dendritic tree of the “average” layer III pyramidal cell in V1, V2, V4, TEO, and TE at 2D, 3W, 3½M, 7M, and adults (AD). Error bars = standard errors.

Somal Areas

Individual cell bodies were drawn, and the somal area was measured in the plane tangential to the cortical layers (Fig. 7). In V1, the largest cell bodies were observed at 3W, being slightly larger than at 2D. The cell bodies were smaller in older infants, being 43% and 34% smaller than the maximum at 3½ and 7M, respectively. Even in the adult, the cell bodies of pyramidal cells in V1 were >40% smaller than those observed at 2D. Likewise, in V2, the largest cell bodies were observed at 3W. The cell bodies became progressively smaller through 3½ and 7M to adulthood. In V4, the largest cell bodies were observed at 3½M, being 56% larger than those at 3W. In TEO and TE, there was a trend for increasingly larger cell bodies from 2D to adulthood. Statistical analysis (one-way ANOVAs) revealed that the size of the cell bodies of pyramidal cells in any given cortical area was significantly different (P < 0.05) across the age groups (V1, F4 = 72.42; V2, F4 = 35.06; V4, F4 = 41.47; TEO, F4 = 34.24; TE, F4 = 22.24).

Figure 7.

Frequency histograms of the size of the cell bodies of layer III pyramidal neurons in V1, V2, V4, TEO, and TE. Arrowheads indicate the means.

Figure 7.

Frequency histograms of the size of the cell bodies of layer III pyramidal neurons in V1, V2, V4, TEO, and TE. Arrowheads indicate the means.

Comparison of the size of the cell bodies among cortical areas at each given age revealed variation in interareal trends with aging (Fig. 7). Cells in V4 had the largest cell bodies at most ages (2D, 3½ months, and adult). At 3W and 7M, cells in area TE had the largest cell bodies. Statistical analysis (one-way ANOVAs) revealed that the size of the cell bodies at any given age was significantly different among cortical areas (P < 0.05) in all animals (2D, F4 = 56.02; 3W, F4 = 5.06; 3½M, F3 = 81.21; 7M, F4 = 66.54; A, F4 = 62.93).

Discussion

In the present investigation, we studied layer III pyramidal cell structure in the primary (V1), second (V2), and fourth (V4) visual areas as well as cytoarchitectonic areas TEO and TE of the inferior temporal cortex in monkeys ranging in age from 2 days old to 4½ years of age (4½Y). We found that cells in all these areas are characterized by different growth profiles. In V1, for example, the largest basal dendritic trees were observed at 2D, whereas in inferior temporal cortex, the largest basal dendritic trees were observed in the adult. In addition, increased branching was observed at different developmental ages among V1, V2, V4, TEO, and TE. Peak spine density occurred in all cortical areas at approximately 3½M. However, because of the different dendritic growth and branching observed with aging among cortical areas, we found differences in patterns of spine growth and pruning in the dendritic trees of cells in V1, V2, V4, TEO, and TE. There was a net decrease in the number of spines in the dendritic trees of cells in V1, V2, and V4 from 2D to adulthood, whereas there was a net increase in the number of spines in the dendritic trees of cells in TEO and TE during this same period. In other words, pruning exceeds spinogenesis in V1, V2, and V4, whereas spinogenesis exceeds pruning in TEO and TE, during the normal course of postnatal development from visual onset to young adulthood.

Size of the Dendritic Trees and Receptive Field Size

Our data in V1, which reveal a decrease in the size of the dendritic trees of pyramidal cells from early in postnatal development to adulthood, are consistent with the data of Boothe et al. (1979) who demonstrated that the basal dendrites of layer III pyramidal cells are longer early in development than in the adult, although their data on stellate cells suggest that maximal dendritic size might be achieved at slightly different ages among cell types and/or cortical layers. These anatomical data are consistent with various aspects of cell function. Movshon et al. (1999, 2000) demonstrated that receptive field sizes of neurons located in the central 5 degrees of the visual representation in V1 decrease in size from early postnatal development to adulthood. In addition, they demonstrated that the spatial resolution of cells in V1 (the highest spatial frequency at which cells give a response of at least 10% of its maximum) increases from birth to adulthood. They also reported a general trend for increasing surround suppression from birth to adulthood (for reviews, see Kiorpes and Movshon 2003; Chino et al. 2004). These changes in receptive field size, spatial acuity, and surround suppression could plausibly be attributed to changes in the geometrical sampling of neurons as their dendritic trees change shape (cf., Sholl 1955; Ferster 1998; Taylor et al. 2000; Vaney and Taylor 2002). Specifically, as the dendritic trees of neurons decrease in size with maturation, they may sample a progressively smaller portion of the visuotopically organized afferent projection and thus have progressively smaller receptive fields. Additionally, by sampling a smaller proportion of the topographic map cells in the adult have increased spatial resolution as defined by their geometrical sampling strategies (for reviews on sampling geometry, see Sholl 1956; Malach 1994; Elston 2003a). However, although consistent with this interpretation, the decrease in the size of the dendritic trees of pyramidal cells cannot account fully for the decrease in the size of their receptive fields (65% and 41%, respectively). Quite possibly, pruning of afferent fibers to V1 during this time (Lund et al. 1977) may account for this difference, although this remains to be determined.

Zhang et al. (2008) reported that in V2, receptive fields of neurons mature later than those in V1 neurons, consistent with our finding that the dendritic trees of pyramidal cells in V2 continue to grow from 2D to 3½M , whereas those in V1 become smaller during this time. Neurons in area TE are not visually responsive until even later in development—about 4 months of age (Rodman et al. 1994). Anatomical connections of TE undergo a protracted period of refinement from birth to adulthood compared with other visual areas (Webster et al. 1991, 1994, 1995; Rodman and Consuelos 1994; Barone et al. 1996; Coogan and Van Essen 1996), and this region becomes myelinated much later in development than V1 (cf., Rodman 1994). Based on the present data, which reveal progressively larger dendritic trees in TEO and TE neurons from birth to adulthood, it might be reasonable to assume that the receptive fields of neurons in inferior temporal cortex become increasingly larger with aging. Longitudinal quantitative studies will be required to provide the required empirical data.

Branching Complexity

Although the dendritic trees of pyramidal cells in V1 were at their largest at 2D, they were most branched at 3W. This age disparity may be attributable to the different functional tasks achieved by size versus branching complexity in the dendritic tree. Although we have discussed above how the size of the dendritic trees may influence the receptive field size of the neuron, branching structure may be important in determining orientation and direction selectivity in V1 (cf., Pettigrew 1974; Tieman and Hirsch 1982; Elston and Rosa 1997; Ferster 1998; Livingstone 1998). Whereas 10-day-old monkeys are already capable of color discrimination, form discrimination only becomes discernable at 3W (Zimmermann 1961). Is it a coincidence that the onset of form discrimination occurs at the time when cells are most branched? Could the increase in the number of branches facilitate compartmentalization of processing within the dendritic tree (Poirazi and Mel 2001; Chklovskii et al. 2004) and allow detection of inputs associated with asymmetric features throughout the dendritic tree?

The temporal sequence of attaining maximum size then maximum branching complexity observed in V1 was not characteristic of extrastriate cortical areas. The greatest branching complexity in the dendritic trees of neurons in V2 was found at 3W, a time when these cells are at their maximum size. Coincident maximum size and maximum branching complexity was also observed in V4 but at 3½M. Cells in TEO and TE attain their greatest branching complexity at 3W and 7M, respectively; yet these cells are characterized by continual dendritic growth from 2D to adulthood. These data suggest that factors mediating the size and branching complexity of the dendritic trees of layer III pyramidal cells may be independent of each other or may interact differently among cortical areas (e.g., Ruchhoeft et al. 1999; Li et al. 2000; Nakayama et al. 2000; Tashiro et al. 2000; Wong et al. 2000; Arendt et al. 2004).

Spinogenesis and Pruning

There are differences in opinion regarding the time course of in vivo spinogenesis, synapse formation, and pruning in the cerebral cortex (Rakic et al. 1986; Huttenlocher and Dabholkar 1997). On the one hand, it has been suggested that synaptogenesis occurs concurrently among cortical areas, whereas on the other hand, it has been suggested that synaptogenesis occurs sequentially (for reviews, see Huttenlocher and Dabholkar 1997; Rakic and Kornack 2001; Guillery 2005). These theories derive from the quantification of the number of synapses per unit neuropil and are not corrected for cell death. Data leading to the former view were obtained from the macaque monkey (Rakic et al. 1986; Bourgeois and Rakic 1993), whereas those supporting the later view were obtained from the human brain (Huttenlocher 1979; Huttenlocher et al. 1982; Huttenlocher and de Courten 1987; Travis et al. 2005).

The present data confirm and expand the former view for the macaque monkey. Specifically, the present data reveal that peak spine density was attained in V1, V2, V4, TEO, and TE at approximately 3½ M. (Note that animals were only sampled at 2 D, 3 W, 3½ M, 7 M, and 4½ Y.) However, the present observations add a new twist to the story: peak spine density varied in magnitude among cells in the different cortical areas (Fig. 5). Furthermore, our estimates of the total number of spines within the dendritic trees of pyramidal cells varied by >3½-fold among cortical areas at the time of peak spine density, due to differences in the size and branching structure of the dendrites (3900 spines in V1 and 14 100 spines in TEO). In addition, there was a net decrease in the number of spines (putative excitatory synapses) within the dendritic trees of layer III pyramidal cells from visual onset to adulthood, as is the case in V1, V2, and V4. This trend, however, is not true for all cortical areas. In TEO and TE, it appears as though more spines are grown from visual onset to 3½M that are then subsequently pruned during maturation to adulthood. A much higher proportion of spines are pruned from the dendritic trees of neurons in V1 (approximately 80%), V2 (77%), and V4 (73%) than in areas TEO and TE (41% and 46%, respectively) from 3½M to adulthood. It remains to be determined whether these trends are characteristic of other neurons in these same cortical areas or if they are specific to layer III pyramidal cells. We have begun a study of infragranular pyramidal cells to investigate this further.

Conclusions

Here, we demonstrated that the dendritic trees of pyramidal cells in V1, V2, V4, TEO, and TE have different growth and atrophy profiles during normal development. We found differences in the timing and rate that branches are grown and pruned from within the dendritic trees among cortical areas. In all cortical areas, we found a trend for increasing spine density along the dendrites from birth to approximately 3½M, beyond which pruning exceeded any further spine growth resulting in a net decrease in the number of spines found within the dendritic trees. The extent of this pruning differed among cortical areas; cells in V1, V2, and V4 actually prune more spines following visual onset than they grow, whereas cells in TEO and TE do not. The result is that cells in the adult V1, V2, and V4 have fewer spines than they are born with, whereas cells in adult TEO and TE have as many as 2-fold the number of spines they are born with. To better comprehend the structural correlates of development and maturation of visual behavior, it is clearly necessary to expand the scope of investigation of developmental cell physiology beyond visual areas of the occipital lobe.

Funding

Japan Science and Technology Agency (Core Research for Evolutional Science and Technology) to I.F. and G.N.E.; Ministry of Education, Culture, Sports, Science, and Technology (Japan) (17022025 to I.F.); Osaka University to I.F.; I Hear Innovation Foundation (Australia) to G.N.E.

We thank Noritaka Ichinohe for his comments on the manuscript. Conflict of Interest: None declared.

References

Anderson
K
Bones
B
Robinson
B
Hass
C
Lee
H
Ford
K
Roberts
TA
Jacobs
B
The morphology of supragranular pyramidal neurons in the human insular cortex: a quantitative Golgi study
Cereb Cortex
 , 
2009
, vol. 
19
 (pg. 
2131
-
2144
)
Arellano
JI
Espinosa
A
Fairen
A
Yuste
R
DeFelipe
J
Non-synaptic dendritic spines in neocortex
Neuroscience
 , 
2007
, vol. 
145
 (pg. 
464
-
469
)
Arendt
T
Gärtner
U
Seeger
G
Barmashenko
G
Palm
K
Mittmann
T
Yan
L
Hummeke
M
Behrbohm
J
Bruckner
MK
, et al.  . 
Neuronal activation of Ras regulates synaptic connectivity
Eur J Neurosci
 , 
2004
, vol. 
19
 (pg. 
2953
-
2966
)
Barone
P
Dehay
C
Berland
M
Kennedy
H
Role of directed growth and target selection in the formation of cortical pathways: prenatal development of the projection of area V2 to V4 in the monkey
J Comp Neurol
 , 
1996
, vol. 
374
 (pg. 
1
-
20
)
Boothe
RG
Greenough
WT
Lund
JS
Wrege
K
A quantitative investigation of spine and dendrite development of neurons in visual cortex (area 17) of Macaca nemistrina monkeys
J Comp Neurol
 , 
1979
, vol. 
186
 (pg. 
473
-
489
)
Bourgeois
J-P
Goldman-Rakic
PS
Rakic
P
Synaptogenesis in the prefrontal cortex of rhesus monkeys
Cereb Cortex
 , 
1994
, vol. 
4
 (pg. 
78
-
96
)
Bourgeois
J-P
Rakic
P
Changes of synaptic density in the primary visual cortex of the macaque monkey from fetal to adult stage
J Neurosci
 , 
1993
, vol. 
13
 (pg. 
2801
-
2820
)
Buhl
EH
Schlote
W
Intracellular lucifer yellow staining and electron microscopy of neurons in slices of fixed epitumourous human cortical tissue
Acta Neuropathol
 , 
1987
, vol. 
75
 (pg. 
140
-
146
)
Casagrande
VA
Kaas
JH
Peters
A
Rockland
KS
The afferent, intrinsic and efferent connections of primary visual cortex in primates
Primary visual cortex in primates
 , 
1994
New York
Plenum
(pg. 
201
-
259
Cerebral cortex. Vol. 10
Chino
YM
Bi
M
Zhang
B
Kaas
JH
Collins
C
Normal and abnormal development of the neuronal response properties in primate visual cortex
The primate visual system
 , 
2004
Boca Raton (FL)
CRC Press
(pg. 
81
-
108
)
Chklovskii
DB
Mel
BW
Svoboda
K
Cortical rewiring and information storage
Nature
 , 
2004
, vol. 
431
 (pg. 
782
-
788
)
Coogan
TA
Van Essen
DC
Development of connections within and between areas V1 and V2 of macaque monkeys
J Comp Neurol
 , 
1996
, vol. 
372
 (pg. 
327
-
342
)
Daniel
PM
Whitteridge
D
The representation of the visual field on the cerebral cortex in monkeys
J Physiol (Lond)
 , 
1961
, vol. 
159
 (pg. 
203
-
221
)
DeFelipe
J
Conti
F
Van Eyck
SL
Manzoni
T
Demonstration of glutamate-positive axon terminals forming asymmetric synapses in cat neocortex
Brain Res
 , 
1988
, vol. 
455
 (pg. 
162
-
165
)
Eayrs
JT
Goodhead
B
Postnatal development of the cerebral cortex in the rat
J Anat
 , 
1959
, vol. 
93
 (pg. 
385
-
402
)
Elston
GN
Pyramidal cells of the frontal lobe: all the more spinous to think with
J Neurosci
 , 
2000
, vol. 
20
 pg. 
RC95
  
(1–4)
Elston
GN
Interlaminar differences in the pyramidal cell phenotype in cortical areas 7m and STP (the superior temporal polysensory area) of the macaque monkey
Exp Brain Res
 , 
2001
, vol. 
138
 (pg. 
141
-
152
)
Elston
GN
Cortical heterogeneity: implications for visual processing and polysensory integration
J Neurocytol
 , 
2002
, vol. 
31
 (pg. 
317
-
335
)
Elston
GN
Kaas
JH
Collins
C
Comparative studies of pyramidal neurons in visual cortex of monkeys
The primate visual system
 , 
2003
Boca Raton (FL)
CRC Press
(pg. 
365
-
385
)
Elston
GN
Cortex, cognition and the cell: new insights into the pyramidal neuron and prefrontal function
Cereb Cortex
 , 
2003
, vol. 
13
 (pg. 
1124
-
1138
)
Elston
GN
Pyramidal cell heterogeneity in the visual cortex of the nocturnal New World owl monkey (Aotus trivirgatus)
Neuroscience
 , 
2003
, vol. 
117
 (pg. 
213
-
219
)
Elston
GN
Benavides-Piccione
R
DeFelipe
J
A study of pyramidal cell structure in the cingulate cortex of the macaque monkey with comparative notes on inferotemporal and primary visual cortex
Cereb Cortex
 , 
2005
, vol. 
15
 (pg. 
64
-
73
)
Elston
GN
Benavides-Piccione
R
Elston
A
DeFelipe
J
Manger
P
Pyramidal cell specialization in the occipitotemporal cortex of the Chacma baboon (Papio ursinus)
Exp Brain Res
 , 
2005
, vol. 
167
 (pg. 
496
-
503
)
Elston
GN
Benavides-Piccione
R
Elston
A
DeFelipe
J
Manger
P
Specialization in pyramidal cell structure in the sensory-motor cortex of the vervet monkey (Cercopithecus pygerythrus)
Neuroscience
 , 
2005
, vol. 
134
 (pg. 
1057
-
1068
)
Elston
GN
Benavides-Piccione
R
Elston
A
DeFelipe
J
Manger
P
Specialization in pyramidal cell structure in the cingulate cortex of the Chacma baboon (Papio ursinus): an intracellular injection study of the posterior and anterior cingulate gyrus with comparative notes on the macaque and vervet monkeys
Neurosci Lett
 , 
2005
, vol. 
387
 (pg. 
130
-
135
)
Elston
GN
Benavides-Piccione
R
Elston
A
Manger
P
DeFelipe
J
Pyramidal cell specialization in the occipitotemporal cortex of the vervet monkey (Cercopithecus pygerythrus)
Neuroreport
 , 
2005
, vol. 
16
 (pg. 
967
-
970
)
Elston
GN
Benavides-Piccione
R
Elston
A
Manger
P
DeFelipe
J
Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on the macaque monkey
Anat Rec A Discov Mol Cell Evol Biol
 , 
2005
, vol. 
286
 (pg. 
854
-
865
)
Elston
GN
Benavides-Piccione
R
Elston
A
Manger
P
DeFelipe
J
Regional specialization in pyramidal cell structure in the limbic cortex of the vervet monkey (Cercopithecus pygerythrus): an intracellular injection study of the anterior and posterior cingulate gyrus
Exp Brain Res
 , 
2005
, vol. 
167
 (pg. 
315
-
323
)
Elston
GN
Elston
A
Casagrande
V
Kaas
JH
Pyramidal neurons of granular prefrontal cortex the galago: complexity in the evolution of the psychic cell in primates
Anat Rec A Discov Mol Cell Evol Biol
 , 
2005
, vol. 
285
 (pg. 
610
-
618
)
Elston
GN
Elston
A
Casagrande
V
Kaas
JH
Areal specialization in pyramidal cell structure in the visual cortex of the tree shrew: a new twist revealed in the evolution of cortical circuitry
Exp Brain Res
 , 
2005
, vol. 
163
 (pg. 
13
-
20
)
Elston
GN
Elston
A
Kaas
JH
Casagrande
V
Regional specialization in pyramidal cell structure in the visual cortex of the galago. An intracellular injection study with comparative notes on New World and Old World monkeys
Brain Behav Evol
 , 
2005
, vol. 
66
 (pg. 
10
-
21
)
Elston
GN
Benavides-Piccione
R
Elston
A
Zietsch
B
DeFelipe
J
Manger
P
Casagrande
V
Kaas
JH
Specializations of the granular prefrontal cortex of primates: implications for cognitive processing
Anat Rec A Discov Mol Cell Evol Biol
 , 
2006
, vol. 
288
 (pg. 
26
-
35
)
Elston
GN
Oga
T
Fujita
I
Spinogenesis and pruning scales among functional hierarchies
J Neurosci
 , 
2009
, vol. 
29
 (pg. 
3271
-
3275
)
Elston
GN
Rockland
K
The pyramidal cell of the sensorimotor cortex of the macaque monkey: phenotypic variation
Cereb Cortex
 , 
2002
, vol. 
10
 (pg. 
1071
-
1078
)
Elston
GN
Rosa
MGP
The occipitoparietal pathway of the macaque monkey: comparison of pyramidal cell morphology in layer III of functionally related cortical visual areas
Cereb Cortex
 , 
1997
, vol. 
7
 (pg. 
432
-
452
)
Elston
GN
Rosa
MGP
Morphological variation of layer III pyramidal neurones in the occipitotemporal pathway of the macaque monkey visual cortex
Cereb Cortex
 , 
1998
, vol. 
8
 (pg. 
278
-
294
)
Elston
GN
Rosa
MGP
Pyramidal cells, patches, and cortical columns: a comparative study of infragranular neurons in TEO, TE, and the superior temporal polysensory area of the macaque monkey
J Neurosci
 , 
2000
, vol. 
20
 pg. 
RC117
  
(1–5)
Elston
GN
Tweedale
R
Rosa
MGP
Cellular heterogeneity in cerebral cortex. A study of the morphology of pyramidal neurones in visual areas of the marmoset monkey
J Comp Neurol
 , 
1999
, vol. 
415
 (pg. 
33
-
51
)
Elston
GN
Tweedale
R
Rosa
MGP
Cortical integration in the visual system of the macaque monkey: large scale morphological differences of pyramidal neurones in the occipital, parietal and temporal lobes
Proc R Soc Lond Ser B
 , 
1999
, vol. 
266
 (pg. 
1367
-
1374
)
Felleman
DJ
Van Essen
DC
Distributed hierarchical processing in primate cerebral cortex
Cereb Cortex
 , 
1991
, vol. 
1
 (pg. 
1
-
47
)
Ferster
D
A sense of direction
Nature
 , 
1998
, vol. 
392
 (pg. 
433
-
434
)
Fujita
I
The inferior temporal cortex: architecture, computation and representation
J Neurocytol
 , 
2002
, vol. 
31
 (pg. 
359
-
371
)
Fujita
I
Fujita
T
Intrinsic connections in the macaque inferior temporal cortex
J Comp Neurol
 , 
1996
, vol. 
368
 (pg. 
467
-
486
)
Gattass
R
Gross
CG
Sandell
JH
Visual topography of V2 in the macaque
J Comp Neurol
 , 
1981
, vol. 
201
 (pg. 
519
-
539
)
Gattass
R
Sousa
APB
Gross
CG
Visuotopic organization and extent of V3 and V4 of the macaque
J Neurosci
 , 
1988
, vol. 
8
 (pg. 
1831
-
1845
)
Guillery
RW
Is postnatal neocortical maturation hierarchical?
Trends Neurosci
 , 
2005
, vol. 
28
 (pg. 
512
-
517
)
Hassler
R
Hassler
R
Stephen
H
Comparative anatomy of the central visual system in day- and night-active primates
Evolution of the forebrain
 , 
1966
Stuttgart (Germany)
Thieme
(pg. 
419
-
434
)
Huttenlocher
PR
Synaptic density in human frontal cortex—developmental changes and effects of aging
Brain Res
 , 
1979
, vol. 
163
 (pg. 
195
-
205
)
Huttenlocher
PR
Dabholkar
AS
Regional differences in synaptogenesis in human cerebral cortex
J Comp Neurol
 , 
1997
, vol. 
387
 (pg. 
167
-
178
)
Huttenlocher
PR
de Courten
C
The development of synapses in striate cortex of man
Hum Neurobiol
 , 
1987
, vol. 
6
 (pg. 
1
-
9
)
Huttenlocher
PR
de Courten
C
Garey
LG
Van der Loos
H
Synaptogenesis in human visual cortex: evidence for synapse elimination during normal development
Neurosci Lett
 , 
1982
, vol. 
33
 (pg. 
247
-
252
)
Jacobs
B
Schall
M
Prather
M
Kapler
E
Driscoll
L
Baca
S
Jacobs
J
Ford
K
Wainwright
M
Treml
M
Regional dendritic and spine variation in human cerebral cortex: a quantitative study
Cereb Cortex
 , 
2001
, vol. 
11
 (pg. 
558
-
571
)
Jacobs
B
Scheibel
AB
Schüz
A
Miller
R
Regional dendritic variation in primate cortical pyramidal cells
Cortical areas: unity and diversity
 , 
2002
London
Taylor and Francis
(pg. 
111
-
131
)
Jan
YN
Jan
LY
Dendrites
Genes Dev
 , 
2001
, vol. 
15
 (pg. 
2627
-
2641
)
Kiorpes
L
Movshon
JA
Chalupa
LM
Werner
JS
Neural limitations on visual development in primates
The visual neurosciences
 , 
2003
New York
The MIT Press
(pg. 
159
-
173
)
Koch
C
Biophysics of computation. Information processing in single neurons
 , 
1999
New York
Oxford University Press
Levitt
JB
Kiper
DC
Movshon
JA
Receptive fields and functional architecture of macaque V2
J Neurophysiol
 , 
1994
, vol. 
71
 (pg. 
2517
-
2542
)
Levitt
JB
Yoshioka
T
Lund
JS
Intrinsic cortical connections in macaque visual area V2: evidence for interactions between different functional streams
J Comp Neurol
 , 
1994
, vol. 
342
 (pg. 
551
-
570
)
Li
Z
Van Aelst
L
Cline
HT
Rho GTPases regulate distinct aspects of dendritic arbor growth in Xenopus central neurons in vivo
Nat Neurosci
 , 
2000
, vol. 
3
 (pg. 
217
-
225
)
Livingstone
MS
Mechanisms of direction selectivity in macaque V1
Neuron
 , 
1998
, vol. 
20
 (pg. 
509
-
526
)
London
M
Häusser
M
Dendritic computation
Ann Rev Neurosci
 , 
2005
, vol. 
28
 (pg. 
503
-
532
)
Lund
JS
Boothe
RG
Lund
RD
Development of neurons in the visual cortex (area 17) of the monkey (Macaca nemistrema): a Golgi study from fetal day 127 to postnatal maturity
J Comp Neurol
 , 
1977
, vol. 
176
 (pg. 
149
-
188
)
Lund
JS
Yoshioka
T
Levitt
JB
Comparison of intrinsic connectivity in different areas of macaque monkey cerebral cortex
Cereb Cortex
 , 
1993
, vol. 
3
 (pg. 
148
-
162
)
Malach
R
Cortical columns as devices for maximizing neuronal diversity
Trends Neurosci
 , 
1994
, vol. 
17
 (pg. 
101
-
104
)
Maunsell
JHR
Newsome
WT
Visual processing in monkey extrastriate cortex
Ann Rev Neurosci
 , 
1987
, vol. 
10
 (pg. 
363
-
401
)
Mel
B
Stuart
G
Spruston
N
Häusser
M
Why have dendrites? A computational perspective
Dendrites
 , 
1999
New York
Oxford University Press
(pg. 
271
-
289
)
Movshon
JA
Kiorpes
L
Cavanaugh
JR
Hawken
MJ
Receptive field properties and surround interactions in V1 neurons in infant macaque monkeys
Soc Neurosci Abstr
 , 
1999
, vol. 
25
 pg. 
1048
 
Movshon
JA
Kiorpes
L
Cavanaugh
JR
Hawken
MJ
Developmental reorganization of receptive field surrounds in V1 neurons in infant macaque monkeys
Investig Ophthalmol Vis Sci
 , 
2000
, vol. 
41
 pg. 
333
 
Nakayama
AY
Harms
MB
Luo
L
Small GTPases Rac and Rho in the maintenance of dendritic spines and branches in hippocampal pyramida neurons
J Neurosci
 , 
2000
, vol. 
20
 (pg. 
5329
-
5338
)
Petanjek
Z
Judas
M
Kostovic
I
Uylings
HB
Lifespan alterations of basal dendritic trees of pyramidal neurons in the human prefrontal cortex: a layer-specific pattern
Cereb Cortex
 , 
2008
, vol. 
18
 (pg. 
915
-
929
)
Petralia
RS
Wang
YX
Wenthold
RJ
Histological and ultrastructural localization of kainate receptor subunits, KA2 and GluR6/7, in the rat nervous system using selective antipeptide antibodies
J Comp Neurol
 , 
1994
, vol. 
349
 (pg. 
85
-
110
)
Petralia
RS
Wang
YX
Wenthold
RJ
The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1
J Neurosci
 , 
1994
, vol. 
14
 (pg. 
6102
-
6120
)
Petralia
RS
Yokotani
N
Wenthold
RJ
Light and electron microscope distribution of the NMDA receptor subunit NMDAR1 in the rat nervous system using a selective anti-peptide antibody
J Neurosci
 , 
1994
, vol. 
14
 (pg. 
667
-
696
)
Pettigrew
JD
The effect of visual experience on the development of stimulus specificity by kitten cortical neurones
J Physiol (Lond)
 , 
1974
, vol. 
237
 (pg. 
49
-
74
)
Poirazi
P
Mel
BW
Impact of active dendrites and structural plasticity on the storage capacity of neural tissue
Neuron
 , 
2001
, vol. 
29
 (pg. 
779
-
796
)
Rakic
P
Bourgeois
J-P
Eckenhoff
MF
Zecevic
N
Goldman-Rakic
PS
Concurrent overproduction of synapses in diverse regions of the primate cerebral cortex
Science
 , 
1986
, vol. 
232
 (pg. 
232
-
235
)
Rakic
P
Kornack
DR
Falk
D
Gibson
KR
Neocortical expansion and elaboration during primate evolution: a view from neuroembryology
Evolutionary anatomy of the primate cerebral cortex
 , 
2001
Cambridge
Cambridge University Press
(pg. 
30
-
56
)
Rodman
HR
Development of inferior temporal cortex in monkey
Cereb Cortex
 , 
1994
, vol. 
5
 (pg. 
484
-
498
)
Rodman
HR
Consuelos
MJ
Cortical projections to anterior inferior temporal cortical cortex in infant macaque monkeys
Vis Neurosci
 , 
1994
, vol. 
11
 (pg. 
119
-
133
)
Roe
AW
T'so
DY
Visual topography in primate V2: multiple representation across functional stripes
J Neurosci
 , 
1995
, vol. 
15
 (pg. 
3689
-
3715
)
Ruchhoeft
ML
Ohnuma
S
McNeill
L
Holt
CE
Harris
WA
The neuronal architecture of Xenopus retinal ganglion cells is sculptured by rho-family GTPases in vivo
J Neurosci
 , 
1999
, vol. 
19
 (pg. 
8454
-
8463
)
Seltzer
B
Pandya
DN
Afferent cortical connections of the superior temporal sulcus and surrounding cortex in the rhesus monkey
Brain Res
 , 
1978
, vol. 
149
 (pg. 
1
-
24
)
Sherwood
CC
Raghanti
MA
Stimpson
CD
Bonar
CJ
de Sousa
AA
Preuss
TM
Hof
PR
Scaling of inhibitory interneurons in areas V1 and V2 of anthropoid primates as revealed by calcium-binding protein immunohistochemistry
Brain Behav Evol
 , 
2007
, vol. 
69
 (pg. 
176
-
195
)
Sholl
DA
The surface area of cortical neurons
J Anat
 , 
1955
, vol. 
89
 (pg. 
571
-
572
)
Sholl
DA
The organization of the cerebral cortex
 , 
1956
London
Methuen
Spruston
N
Pyramidal neurons: dendritic structure and synaptic integration
Nat Rev Neurosci
 , 
2008
, vol. 
9
 (pg. 
206
-
221
)
Tashiro
A
Minden
A
Yuste
R
Regulation of dendritic spine morphology by the Rho family of small GTPases: antagonistic roles of Rac and Rho
Cereb Cortex
 , 
2000
, vol. 
10
 (pg. 
927
-
938
)
Taylor
WR
He
S
Levick
WR
Vaney
DI
Dendritic computation of direction selectivity by retinal ganglion cells
Science
 , 
2000
, vol. 
289
 (pg. 
2347
-
2350
)
Tieman
SB
Hirsch
HVB
Exposure to lines of only one orientation modifies dendritic morphology of cells in visual cortex of the cat
J Comp Neurol
 , 
1982
, vol. 
211
 (pg. 
353
-
362
)
Travis
K
Ford
K
Jacobs
B
Regional dendritic variation in neonatal human cortex: a quantitative Golgi study
Dev Neurosci
 , 
2005
, vol. 
27
 (pg. 
277
-
287
)
Treves
A
Frontal latching networks: a possible neural basis for infinite recursion
Cogn Neuropsychol
 , 
2005
, vol. 
22
 (pg. 
276
-
291
)
Valverde
F
Apical dendritic spines of the visual cortex and light deprivation in the mouse
Exp Brain Res
 , 
1967
, vol. 
3
 (pg. 
337
-
352
)
Vaney
DI
Taylor
WR
Direction selectivity in the retina
Curr Opin Neurobiol
 , 
2002
, vol. 
12
 (pg. 
405
-
410
)
Webster
MJ
Bachevalier
J
Ungerleider
LG
Connections of inferior temporal areas TEO and TE with parietal and frontal cortex in macaque monkeys
Cereb Cortex
 , 
1994
, vol. 
4
 (pg. 
470
-
483
)
Webster
MJ
Bachevalier
J
Ungerleider
LG
Transient subcortical connections of inferior temporal areas TEO and TE in infant macaque monkeys
J Comp Neurol
 , 
1995
, vol. 
352
 (pg. 
213
-
226
)
Webster
MJ
Ungerleider
LG
Bachevalier
J
Connections of inferior temporal areas TE and TEO with medial temporal-lobe structures in infant and adult monkeys
J Neurosci
 , 
1991
, vol. 
11
 (pg. 
1095
-
1116
)
Wong
WT
Faulkner-Jones
BE
Sanes
JR
Wong
RO
Rapid dendritic remodeling in the developing retina: dependence on neurotransmission and reciprocal regulation by Rac and Rho
J Neurosci
 , 
2000
, vol. 
20
 (pg. 
5024
-
5036
)
Yoshioka
T
Levitt
JB
Lund
JS
Intrinsic lattice connections of macaque monkey visual cortical area V4
J Neurosci
 , 
1992
, vol. 
12
 (pg. 
2785
-
2802
)
Yukie
M
Sakata
H
Mikami
A
Fuster
J
Organization of visual afferent connections to inferior temporal cortex, area TE, in the macaque monkey
The association cortex, structure and function
 , 
1997
Amsterdam
Harwood Academic Publishers
(pg. 
247
-
258
)
Zhang
B
Smith
EL
3rd
Chino
YM
Postnatal development of onset transient responses in macaque V1 and V2 neurons
J Neurophysiol
 , 
2008
, vol. 
100
 (pg. 
1476
-
1487
)
Zimmermann
RR
Analysis of discrimination learning capacities in the infant rhesus monkey
J Comp Physiol Psychol
 , 
1961
, vol. 
54
 (pg. 
1
-
10
)