Postnatal Dendritic Growth and Spinogenesis of Layer-V Pyramidal Cells Differ between Visual, Inferotemporal, and Prefrontal Cortex of the Macaque Monkey.

Pyramidal cells in the primate cerebral cortex, particularly those in layer III, exhibit regional variation in both the time course and magnitude of postnatal growth and pruning of dendrites and spines. Less is known about the development of pyramidal cell dendrites and spines in other cortical layers. Here we studied dendritic morphology of layer-V pyramidal cells in primary visual cortex (V1, sensory), cytoarchitectonic area TE in the inferotemporal cortex (sensory association), and granular prefrontal cortex (Walker's area 12, executive) of macaque monkeys at the ages of 2 days, 3 weeks, 3.5 months, and 4.5 years. We found that changes in the basal dendritic field area of pyramidal cells were different across the three areas. In V1, field size became smaller over time (largest at 2 days, half that size at 4.5 years), in TE it did not change, and in area 12 it became larger over time (smallest at 2 days, 1.5 times greater at 4.5 years). In V1 and TE, the total number of branch points in the basal dendritic trees was similar between 2 days and 4.5 years, while in area 12 the number was greater in the adult monkeys than in the younger ones. Spine density peaked at 3 weeks and declined in all areas by adulthood, with V1 exhibiting a faster decline than area TE or area 12. Estimates of the total number of spines in the dendritic trees revealed that following the onset of visual experience, pyramidal cells in V1 lose more spines than they grow, whereas those in TE and area 12 grow more spines than they lose during the same period. These data provide further evidence that the process of synaptic refinement in cortical pyramidal cells differs not only according to time, but also location within the cortex. Furthermore, given the previous finding that layer-III pyramidal cells in all these areas exhibit the highest density and total number of spines at 3.5 months, the current results indicate that pyramidal cells in layers III and V develop spines at different rates.

Pyramidal cell development: postnatal spinogenesis, dendritic growth, axon growth, and electrophysiology.

Here we review recent findings related to postnatal spinogenesis, dendritic and axon growth, pruning and electrophysiology of neocortical pyramidal cells in the developing primate brain. Pyramidal cells in sensory, association and executive cortex grow dendrites, spines and axons at different rates, and vary in the degree of pruning. Of particular note is the fact that pyramidal cells in primary visual area (V1) prune more spines than they grow during postnatal development, whereas those in inferotemporal (TEO and TE) and granular prefrontal cortex (gPFC; Brodmann's area 12) grow more than they prune. Moreover, pyramidal cells in TEO, TE and the gPFC continue to grow larger dendritic territories from birth into adulthood, replete with spines, whereas those in V1 become smaller during this time. The developmental profile of intrinsic axons also varies between cortical areas: those in V1, for example, undergo an early proliferation followed by pruning and local consolidation into adulthood, whereas those in area TE tend to establish their territory and consolidate it into adulthood with little pruning. We correlate the anatomical findings with the electrophysiological properties of cells in the different cortical areas, including membrane time constant, depolarizing sag, duration of individual action potentials, and spike-frequency adaptation. All of the electrophysiological variables ramped up before 7 months of age in V1, but continued to ramp up over a protracted period of time in area TE. These data suggest that the anatomical and electrophysiological profiles of pyramidal cells vary among cortical areas at birth, and continue to diverge into adulthood. Moreover, the data reveal that the "use it or lose it" notion of synaptic reinforcement may speak to only part of the story, "use it but you still might lose it" may be just as prevalent in the cerebral cortex.

Pyramidal cells in V1 of African rodents are bigger, more branched and more spiny than those in primates.

Pyramidal cells are characterized by markedly different sized dendritic trees, branching patterns, and spine density across the cortical mantle. Moreover, pyramidal cells have been shown to differ in structure among homologous cortical areas in different species; however, most of these studies have been conducted in primates. Whilst pyramidal cells have been quantified in a few cortical areas in some other species there are, as yet, no uniform comparative data on pyramidal cell structure in a homologous cortical area among species in different Orders. Here we studied layer III pyramidal cells in V1 of three species of rodents, the greater cane rat, highveld gerbil, and four-striped mouse, by the same methodology used to sample data from layer III pyramidal cells in primates. The data reveal markedly different trends between rodents and primates: there is an appreciable increase in the size, branching complexity, and number of spines in the dendritic trees of pyramidal cells with increasing size of V1 in the brain in rodents, whereas there is relatively little difference in primates. Moreover, pyramidal cells in rodents are larger, more branched and more spinous than those in primates. For example, the dendritic trees of pyramidal cells in V1 of the adult cane rat are nearly three times larger, and have more than 10 times the number of spines in their basal dendritic trees, than those in V1 of the adult macaque (7900 and 600, respectively), which has a V1 40 times the size that of the cane rat. It remains to be determined to what extent these differences may result from development or reflect evolutionary and/or processing specializations.

Spinogenesis and Pruning in the Anterior Ventral Inferotemporal Cortex of the Macaque Monkey: An Intracellular Injection Study of Layer III Pyramidal Cells.

Pyramidal cells grow and mature at different rates among different cortical areas in the macaque monkey. In particular, differences across the areas have been reported in both the timing and magnitude of growth, branching, spinogenesis, and pruning in the basal dendritic trees of cells in layer III. Presently available data suggest that these different growth profiles reflect the type of functions performed by these cells in the adult brain. However, to date, studies have focused on only a relatively few cortical areas. In the present investigation we quantified the growth of the dendritic trees of layer III pyramidal cells in the anterior ventral portion of cytoarchitectonic area TE (TEav) to better comprehend developmental trends in the cerebral cortex. We quantified the growth and branching of the dendrities, and spinogenesis and pruning of spines, from post-natal day 2 (PND2) to four and a half years of age. We found that the dendritic trees increase in size from PND2 to 7 months of age and thereafter became smaller. The dendritic trees became increasingly more branched from PND2 into adulthood. There was a two-fold increase in the number of spines in the basal dendritic trees of pyramidal cells from PND2 to 3.5 months of age and then a 10% net decrease in spine number into adulthood. Thus, the growth profile of layer III pyramidal cells in the anterior ventral portion of the inferotemporal cortex differs to that in other cortical areas associated with visual processing.

Pyramidal cells in prefrontal cortex of primates: marked differences in neuronal structure among species.

The most ubiquitous neuron in the cerebral cortex, the pyramidal cell, is characterized by markedly different dendritic structure among different cortical areas. The complex pyramidal cell phenotype in granular prefrontal cortex (gPFC) of higher primates endows specific biophysical properties and patterns of connectivity, which differ from those in other cortical regions. However, within the gPFC, data have been sampled from only a select few cortical areas. The gPFC of species such as human and macaque monkey includes more than 10 cortical areas. It remains unknown as to what degree pyramidal cell structure may vary among these cortical areas. Here we undertook a survey of pyramidal cells in the dorsolateral, medial, and orbital gPFC of cercopithecid primates. We found marked heterogeneity in pyramidal cell structure within and between these regions. Moreover, trends for gradients in neuronal complexity varied among species. As the structure of neurons determines their computational abilities, memory storage capacity and connectivity, we propose that these specializations in the pyramidal cell phenotype are an important determinant of species-specific executive cortical functions in primates.

Spinogenesis and pruning in the primary auditory cortex of the macaque monkey (Macaca fascicularis): an intracellular injection study of layer III pyramidal cells.

Recently we demonstrated that neocortical pyramidal cells in visual, visual association and prefrontal cortex of the macaque monkey are characterised by different growth, branching, spinogenesis and pruning during development. Some neurons, such as those in the primary visual area, prune more spines than they grow following sensory onset, while others such as those in area TE grow more than they prune. To what extent these different neuronal growth profiles may vary among cortical areas remains to be determined. To better comprehend the nature and extent of these regional differences in pyramidal cell growth profiles we expanded the bases for comparison by studying neurons in the primary auditory cortex (A1). We found that pyramidal cells in A1 continue to grow their basal dendritic trees beyond the peak period of spinogenesis (3(1)/(2) months) up until at least 7 months of age. Likewise, the most prolific branching patterns were observed in the dendritic trees of pyramidal cells at 7 months of age. These data reveal that the basal dendritic trees of cells in A1 continue to grow for a much longer period, and attain almost double the number of spines, as compared with those in V1. Such differences in the growth profiles of neocortical pyramidal cells among cortical areas may influence therapeutic outcomes when applying new technologies such as neurotrophic delivery devices or stem cell therapy.

Spinogenesis and pruning from early visual onset to adulthood: an intracellular injection study of layer III pyramidal cells in the ventral visual cortical pathway of the macaque monkey.

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.

Morphological variability of NADPH diaphorase neurons across areas V1, V2, and V3 of the common agouti.

Previous studies have shown a noticeable phenotypic diversity for pyramidal cells among cortical areas in the cerebral cortex. Both the extent and systematic nature of this variation suggests a correlation with particular aspects of cortical processing. Nevertheless, regional variations in the morphology of inhibitory cells have not been evaluated with the same detail. In the present study we performed a 3D morphometric analysis of 120 NADPH diaphorase (NADPH-d) type I neurons in the visual cortex of a South American Hystricomorph rodent, the diurnal agouti (Dasyprocta sp.). We found significant differences in morphology of NADPH-d type I neurons among visual cortical areas: cells became progressively larger and more branched from V1 to V2 and V3. Presumably, the specialized morphology of these cells is correlated with different sampling geometry and function. The data suggest that area-specific specializations of cortical inhibitory circuitry are also present in rodents.

Maximization of the connectivity repertoire as a statistical principle governing the shapes of dendritic arbors.

The shapes of dendritic arbors are fascinating and important, yet the principles underlying these complex and diverse structures remain unclear. Here, we analyzed basal dendritic arbors of 2,171 pyramidal neurons sampled from mammalian brains and discovered 3 statistical properties: the dendritic arbor size scales with the total dendritic length, the spatial correlation of dendritic branches within an arbor has a universal functional form, and small parts of an arbor are self-similar. We proposed that these properties result from maximizing the repertoire of possible connectivity patterns between dendrites and surrounding axons while keeping the cost of dendrites low. We solved this optimization problem by drawing an analogy with maximization of the entropy for a given energy in statistical physics. The solution is consistent with the above observations and predicts scaling relations that can be tested experimentally. In addition, our theory explains why dendritic branches of pyramidal cells are distributed more sparsely than those of Purkinje cells. Our results represent a step toward a unifying view of the relationship between neuronal morphology and function.

Spinogenesis and pruning scales across functional hierarchies.

Spinogenesis and synaptic pruning during development are widely believed to subserve connectional specificity in the mature CNS via Hebbian-type reinforcement. Refinement of neuronal circuit through this "use it or lose it" principle is considered critical for brain development. Here we demonstrate that the magnitude of spinogenesis and pruning in the basal dendritic trees of pyramidal cells differ dramatically among sensory, association, and executive cortex. Moreover, somewhat counterintuitively, we demonstrate that the dendritic trees of pyramidal cells in the primary visual area actually lose more spines than they grow following the onset of visual experience. The present findings reveal that the process of synaptic refinement differs not only according to time, but also location.

Specialization of pyramidal cell structure in the visual areas V1, V2 and V3 of the South American rodent, Dasyprocta primnolopha.

Marked phenotypic variation has been reported in pyramidal cells in the primate cerebral cortex. These extent and systematic nature of these specializations suggest that they are important for specialized aspects of cortical processing. However, it remains unknown as to whether regional variations in the pyramidal cell phenotype are unique to primates or if they are widespread amongst mammalian species. In the present study we determined the receptive fields of neurons in striate and extrastriate visual cortex, and quantified pyramidal cell structure in these cortical regions, in the diurnal, large-brained, South American rodent Dasyprocta primnolopha. We found evidence for a first, second and third visual area (V1, V2 and V3, respectively) forming a lateral progression from the occipital pole to the temporal pole. Pyramidal cell structure became increasingly more complex through these areas, suggesting that regional specialization in pyramidal cell phenotype is not restricted to primates. However, cells in V1, V2 and V3 of the agouti were considerably more spinous than their counterparts in primates, suggesting different evolutionary and developmental influences may act on cortical microcircuitry in rodents and primates.

Ipsilateral corticocortical projections to the primary and middle temporal visual areas of the primate cerebral cortex: area-specific variations in the morphology of connectionally identified pyramidal cells.

We quantified the morphology of over 350 pyramidal neurons with identified ipsilateral corticocortical projections to the primary (V1) and middle temporal (MT) visual areas of the marmoset monkey, following intracellular injection of Lucifer Yellow into retrogradely labelled cells. Paralleling the results of studies in which randomly sampled pyramidal cells were injected, we found that the size of the basal dendritic tree of connectionally identified cells differed between cortical areas, as did the branching complexity and spine density. We found no systematic relationship between dendritic tree structure and axon target or length. Instead, the size of the basal dendritic tree increased roughly in relation to increasing distance from the occipital pole, irrespective of the length of the connection or the cortical layer in which the neurons were located. For example, cells in the second visual area had some of the smallest and least complex dendritic trees irrespective of whether they projected to V1 or MT, while those in the dorsolateral area (DL) were among the largest and most complex. We also observed that systematic differences in spine number were more marked among V1-projecting cells than MT-projecting cells. These data demonstrate that the previously documented systematic differences in pyramidal cell morphology between areas cannot simply be attributed to variable proportions of neurons projecting to different targets, in the various areas. Moreover, they suggest that mechanisms intrinsic to the area in which neurons are located are strong determinants of basal dendritic field structure.

Specializations of the granular prefrontal cortex of primates: implications for cognitive processing.

The biological underpinnings of human intelligence remain enigmatic. There remains the greatest confusion and controversy regarding mechanisms that enable humans to conceptualize, plan, and prioritize, and why they are set apart from other animals in their cognitive abilities. Here we demonstrate that the basic neuronal building block of the cerebral cortex, the pyramidal cell, is characterized by marked differences in structure among primate species. Moreover, comparison of the complexity of neuron structure with the size of the cortical area/region in which the cells are located revealed that trends in the granular prefrontal cortex (gPFC) were dramatically different to those in visual cortex. More specifically, pyramidal cells in the gPFC of humans had a disproportionately high number of spines. As neuron structure determines both its biophysical properties and connectivity, differences in the complexity in dendritic structure observed here endow neurons with different computational abilities. Furthermore, cortical circuits composed of neurons with distinguishable morphologies will likely be characterized by different functional capabilities. We propose that 1. circuitry in V1, V2, and gPFC within any given species differs in its functional capabilities and 2. there are dramatic differences in the functional capabilities of gPFC circuitry in different species, which are central to the different cognitive styles of primates. In particular, the highly branched, spinous neurons in the human gPFC may be a key component of human intelligence.

Pyramidal cell specialization in the occipitotemporal cortex of the Chacma baboon (Papio ursinus).

Pyramidal cell structure varies systematically in occipitotemporal visual areas in monkeys. The dendritic trees of pyramidal cells, on average, become larger, more branched and more spinous with progression from the primary visual area (V1) to the second visual area (V2), the fourth (V4, or dorsolateral DL visual area) and inferotemporal (IT) cortex. Presently available data reveal that the extent of this increase in complexity parallels the expansion of occipitotemporal cortex. Here we extend the basis for comparison by studying pyramidal cell structure in occipitotemporal cortical areas in the chacma baboon. We found a systematic increase in the size of and branching complexity in the basal dendritic trees, as well as a progressive increase in the spine density along the basal dendrites of layer III pyramidal cells through V1, V2 and V4. These data suggest that the trend for more complex pyramidal cells with anterior progression through occipitotemporal visual areas is not a feature restricted to monkeys and prosimians, but is a widespread feature of occipitotemporal cortex in primates.

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.

The pyramidal cell phenotype varies quite dramatically in structure among different cortical areas in the primate brain. Comparative studies in visual cortex, in particular, but also in sensorimotor and prefrontal cortex, reveal systematic trends for pyramidal cell specialization in functionally related cortical areas. Moreover, there are systematic differences in the extent of these trends between different primate species. Recently we demonstrated differences in pyramidal cell structure in the cingulate cortex of the macaque monkey; however, in the absence of other comparative data it remains unknown as to whether the neuronal phenotype differs in cingulate cortex between species. Here we extend the basis for comparison by studying the structure of the basal dendritic trees of layer III pyramidal cells in the posterior and anterior cingulate gyrus of the vervet monkey (Brodmann's areas 23 and 24, respectively). Cells were injected with Lucifer Yellow in flat-mounted cortical slices, and processed for a light-stable DAB reaction product. Size, branching pattern, and spine density of basal dendritic arbors were determined, and somal areas measured. As in the macaque monkey, we found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). In addition, the extent of the difference in pyramidal cell structure between these two cortical regions was less in the vervet monkey than in the macaque monkey.

Specialization in pyramidal cell structure in the sensory-motor cortex of the Chacma baboon (Papio ursinus) with comparative notes on macaque and vervet monkeys.

The systematic study of pyramidal cell structure has revealed new insights into specialization of the phenotype in the primate cerebral cortex. Regional specialization in the neuronal phenotype may influence patterns of connectivity and the computational abilities of the circuits they compose. The comparative study of pyramidal cells in homologous cortical areas is beginning to yield data on the evolution and development of such specialized circuitry in the primate cerebral cortex. Recently, we have focused our efforts on sensory-motor cortex. Based on our intracellular injection methodology, we have demonstrated a progressive increase in the size of, the branching structure in, and the spine density of the basal dendritic trees of pyramidal cells through somatosensory areas 3b, 1, 2, 5, and 7 in the macaque and vervet monkeys. In addition, we have shown that pyramidal cells in premotor area 6 are larger, more branched, and more spinous than those in the primary motor cortex (MI or area 4) in the macaque monkey, vervet monkey, and baboon. Here we expand the basis for comparison by studying the basal dendritic trees of layer III pyramidal cells in these same sensory-motor areas in the chacma baboon. The baboon was selected because it has a larger cerebral cortex than either the macaque or vervet monkeys; motor cortex has expanded disproportionately in these three species; and motor cortex in the baboon reportedly has differentiated to include a new cortical area not present in either the macaque or vervet monkeys. We found, as in monkeys, a progressive increase in the morphological complexity of pyramidal cells through areas 3b, 5, and 7, as well as from area 4 to area 6, suggesting that areal specialization in microcircuitry was likely to be present in a common ancestor of primates. In addition, we found subtle differences in the extent of the interareal differences in pyramidal cell structure between homologous cortical areas in the three species.

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.

This study forms part of an ongoing investigation of pyramidal cell structure in the cingulate cortex of primates. Recently we have demonstrated that layer III pyramidal cells in the anterior cingulate gyrus are considerably larger, more branched and more spinous than those in the posterior cingulate gyrus (areas 24 and 23, respectively) in the macaque and vervet monkeys. Moreover, the extent of the interareal difference in specialization in pyramidal cell structure differed between the two species. These data suggest that pyramidal cell circuitry may have evolved differently in these closely related species. Presently there are too few data to speculate on what is selecting for this specialization in structure. Here we extend the basis for comparison by studying pyramidal cell structure in cingulate gyrus of the Chacma baboon (Papio ursinus). Methodology used here is the same as that for our previous studies: intracellular injection of Lucifer Yellow in flat-mounted cortical slices. We found that pyramidal cells in anterior cingulate gyrus (area 24) were more branched and more spinous than those in posterior cingulate gyrus (area 23). Moreover, the complexity in pyramidal cell structure in both the anterior and posterior cingulate gyrus of the baboon differed to that in the corresponding regions in either the macaque or vervet monkeys.

Pyramidal cell specialization in the occipitotemporal cortex of the vervet monkey.

Pyramidal cells were injected intracellularly in fixed, flat-mounted cortical slices taken from the first and fourth visual areas (V1 and V4, respectively) and cytoarchitectonic areas TEO and TE of two age and gender-matched vervet monkeys and the size, branching complexity and spine density of their basal dendritic trees determined. In both animals, we found marked differences in the pyramidal cell phenotype between cortical areas. More specifically, a consistent trend for larger, more branched and more spinous pyramidal cells with progression through V1, V4, TEO and TE was observed. These findings support earlier reports of interareal specialization in pyramidal cell structure in occipitotemporal visual areas in the macaque monkey.

Pyramidal neurons of granular prefrontal cortex of the galago: complexity in evolution of the psychic cell in primates.

Typically, cognitive abilities of humans have been attributed to their greatly expanded cortical mantle, granular prefrontal cortex (gPFC) in particular. Recently we have demonstrated systematic differences in microstructure of gPFC in different species. Specifically, pyramidal cells in adult human gPFC are considerably more spinous than those in the gPFC of the macaque monkey, which are more spinous than those in the gPFC of marmoset and owl monkeys. As most cortical dendritic spines receive at least one excitatory input, pyramidal cells in these different species putatively receive different numbers of inputs. These differences in the gPFC pyramidal cell phenotype may be of fundamental importance in determining the functional characteristics of prefrontal circuitry and hence the cognitive styles of the different species. However, it remains unknown as to why the gPFC pyramidal cell phenotype differs between species. Differences could be attributed to, among other things, brain size, relative size of gPFC, or the lineage to which the species belong. Here we investigated pyramidal cells in the dorsolateral gPFC of the prosimian galago to extend the basis for comparison. We found these cells to be less spinous than those in human, macaque, and marmoset.

Regional specialization in pyramidal cell structure in the visual cortex of the galago: an intracellular injection study of striate and extrastriate areas with comparative notes on new world and old world monkeys.

Recent studies have revealed marked differences in the basal dendritic structure of layer III pyramidal cells in the cerebral cortex of adult simian primates. In particular, there is a consistent trend for pyramidal cells of increasing complexity with anterior progression through occipitotemporal cortical visual areas. These differences in pyramidal cell structure, and their systematic nature, are believed to be important for specialized aspects of visual processing within, and between, cortical areas. However, it remains unknown whether this regional specialization in the pyramidal cell phenotype is unique to simians, is unique to primates in general or is widespread amongst mammalian species. In the present study we investigated pyramidal cell structure in the prosimian galago (Otolemur garnetti). We found, as in simians, that the basal dendritic arbors of pyramidal cells differed between cortical areas. More specifically, pyramidal cells became progressively more spinous through the primary (V1), second (V2), dorsolateral (DL) and inferotemporal (IT) visual areas. Moreover, pyramidal neurons in V1 of the galago are remarkably similar to those in other primate species, in spite of large differences in the sizes of this area. In contrast, pyramidal cells in inferotemporal cortex are quite variable among primate species. These data suggest that regional specialization in pyramidal cell phenotype was a likely feature of cortex in a common ancestor of simian and prosimian primates, but the degree of specialization varies between species.