Guy N. Elston

Distribution and patterns of connectivity of interneurons containing calbindin, calretinin, and parvalbumin in visual areas of the occipital and temporal lobes of the macaque monkey

Immunocytochemical techniques were used to examine the distribution of double‐bouquet cells and chandelier cells that were immunoreactive (‐ir) for the calcium‐binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV) in the primary visual area (V1), the second visual area (V2), and cytoarchitectonic area TE in the macaque monkey. Furthermore, the connections between CB‐, CR‐, and PV‐ir neurons in these visual areas were investigated at the light microscope level by using a dual‐immunocytochemical staining procedure. The most significant findings were three‐fold. First, the number and distribution of CB‐ir and CR‐ir double‐bouquet cells and PV‐ir chandelier cells differed considerably between different visual areas. In particular, the different distribution of double‐bouquet cells was illustrated dramatically at the V1/V2 border, where CB‐ir double‐bouquet axons were very few or lacking in V1 but were very numerous in V2. Furthermore, PV‐ir chandelier cell terminals were relatively sparse in V1, more frequent in V2, and most frequent in area TE. Second, the percentage of CB‐, CR‐, and PV‐ir neurons receiving multiple contacts on their somata and proximal dendrites from other calcium‐binding protein neurons varied between 22% and 85%. The highest percentage of contacts found between immunolabelled cells and multiterminals were for the combinations CR/CB (76–85%; percent of cells immunoreactive for CB that were innervated by multiterminals immunoreactive for CR), followed by the combination PV/CR (42–48%), and then by the other combinations that had similar percentages (22–32% for CR/PV; 26–37% for CB/CR; 29–42% for CR/PV). Third, differences in the relative proportions of CB, CR, and PV terminals in contact with CB‐, CR‐, and PV‐ir neurons were consistent between the different cortical areas studied. Thus, certain characteristics of intraareal circuits differ, whereas others remain similar, in different areas of the occipitotemporal visual pathway. The differences may represent regional specializations related to the different processing of visual stimuli, whereas the similarities may be attributed to general functional requisites for interneuronal circuitry. J. Comp. Neurol. 412:515–526, 1999.

Cortical heterogeneity: implications for visual processing and polysensory integration.

Recent studies have revealed substantial variation in pyramidal cell structure in different cortical areas. Moreover, cell morphology has been shown to vary in a systematic fashion such that cells in visual association areas are larger and more spinous than those in the primary visual area. Various aspects of these structural differences appear to be important in influencing neuronal function. At the cellular level, differences in the branching patterns in the dendritic arbour may allow for varying degrees of non-linear compartmentalisation. Differences in total dendritic length and spine number may determine the number of inputs integrated by individual cells. Variations in spine density and geometry may affect cooperativity of inputs and shunting inhibition, and the tangential dimension of the dendritic arbours may determine sampling strategies within cortex. At the systems level, regional variation in pyramidal cell structure may determine thedegree of recurrent excitation through reentrant circuits influencing the discharge properties of individual neurones and the functional signature of the circuits they compose. The ability of pyramidal neurones in visual areas of the parietal and temporal lobes to integrate large numbers of excitatory inputs may also facilitate cortical binding. Here I summarise what I consider to be among the most salient, and testable, aspects of an inter-relationship between morphological and functional heterogeneity in visual cortex.

Visuotopic organisation and neuronal response selectivity for direction of motion in visual areas of the caudal temporal lobe of the marmoset monkey (Callithrix jacchus): Middle temporal area, middle temporal crescent, and surrounding cortex

On the basis of extracellular recordings in marmoset monkeys, we report on the organisation of the middle temporal area (MT) and the surrounding middle temporal crescent (MTc). Area MT is approximately 5‐mm long and 2‐mm wide, whereas the MTc forms a crescent‐shaped band of cortex 1‐mm wide. Neurones in area MT form a first‐order representation of the contralateral hemifield, whereas those in the MTc form a second‐order representation with a field discontinuity near the horizontal meridian. The representation of the vertical meridian forms the border between area MT and the MTc. In both areas, the fovea is represented ventrocaudally, and the visual field periphery is represented dorsorostrally. Analysis of single units revealed that 86% of cells in area MT show a strong selectivity for the direction of motion of visual stimuli. The proportion of direction‐selective cells in the MTc (53%), whereas lower than that in area MT, is much higher than that observed in most other visual areas. Neurones in the cortex immediately rostral to area MT and the MTc are direction selective, with receptive fields predominantly located in the visual field periphery. In contrast, only a minority of the cells in the cortex ventral to the MTc are direction selective, and their receptive fields emphasise central vision. The results suggest that the MTc is functionally closely related to area MT, and distinct from the areas forming the dorsolateral complex. The MTc may have a role in combining information about motion in the visual field, processed by area MT, with information about stimulus shape, processed by the dorsolateral complex. J. Comp. Neurol. 393:505–527, 1998.

Density and morphology of dendritic spines in mouse neocortex

Dendritic spines of pyramidal cells are the main postsynaptic targets of cortical excitatory synapses and as such, they are fundamental both in neuronal plasticity and for the integration of excitatory inputs to pyramidal neurons. There is significant variation in the number and density of dendritic spines among pyramidal cells located in different cortical areas and species, especially in primates. This variation is believed to contribute to functional differences reported among cortical areas. In this study, we analyzed the density of dendritic spines in the motor, somatosensory and visuo-temporal regions of the mouse cerebral cortex. Over 17,000 individual spines on the basal dendrites of layer III pyramidal neurons were drawn and their morphologies compared among these cortical regions. In contrast to previous observations in primates, there was no significant difference in the density of spines along the dendrites of neurons in the mouse. However, systematic differences in spine dimensions (spine head size and spine neck length) were detected, whereby the largest spines were found in the motor region, followed by those in the somatosensory region and those in visuo-temporal region.

Cortical integration in the visual system of the macaque monkey: large-scale morphological differences in the pyramidal neurons in the occipital, parietal and temporal lobes

Layer III pyramidal neurons were injected with Lucifer yellow in tangential cortical slices taken from the inferior temporal cortex (area TE) and the superior temporal polysensory (STP) area of the macaque monkey. Basal dendritic field areas of layer III pyramidal neurons in area STP are significantly larger, and their dendritic arborizations more complex, than those of cells in area TE. Moreover, the dendritic fields of layer III pyramidal neurons in both STP and TE are many times larger and more complex than those in areas forming ‘lower’ stages in cortical visual processing, such as the first (V1), second (V2), fourth (V4) and middle temporal (MT) visual areas. By combining data on spine density with those of Sholl analyses, we were able to estimate the average number of spines in the basal dendritic field of layer III pyramidal neurons in each area. These calculations revealed a 13–fold difference in the number of spines in the basal dendritic field between areas STP and V1 in animals of similar age. The large differences in complexity of the same kind of neuron in different visual areas go against arguments for isopotentiality of different cortical regions and provide a basis that allows pyramidal neurons in temporal areas TE and STP to integrate more inputs than neurons in more caudal visual areas.

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.

Cellular heterogeneity in cerebral cortex: A study of the morphology of pyramidal neurones in visual areas of the marmoset monkey

The morphological characteristics of the basal dendritic fields of layer III pyramidal neurones were determined in visual areas in the occipital, parietal, and temporal lobes of adult marmoset monkeys by means of intracellular iontophoretic injection of Lucifer yellow. Neurones in the primary visual area (V1) had the least extensive and least complex (as determined by Sholl analysis) dendritic trees, followed by those in the second visual area (V2). There was a progressive increase in size and complexity of dendritic trees with rostral progression from V1 and V2, through the “ventral stream,” including the dorsolateral area (DL) and the caudal and rostral subdivisions of inferotemporal cortex (ITc and ITr, respectively). Neurones in areas of the dorsal stream, including the dorsomedial (DM), dorsoanterior (DA), middle temporal (MT), and posterior parietal (PP) areas, were similar in size and complexity but were larger and more complex than those in V1 and V2. Neurones in V1 had the lowest spine density, whereas neurones in V2, DM, DA, and PP had similar spine densities. Neurones in MT and inferotemporal cortex had relatively high spine densities, with those in ITr having the highest spine density of all neurones studied. Calculations based on the size, number of branches, and spine densities revealed that layer III pyramidal neurones in ITr have 7.4 times more spines on their basal dendritic fields than those in V1. The differences in the extent of, and the number of spines in, the basal dendritic fields of layer III pyramidal neurones in the different visual areas suggest differences in the ability of neurones to integrate excitatory and inhibitory inputs. The differences in neuronal morphology between visual areas, and the consistency in these differences across New World and Old World monkey species, suggest that they reflect fundamental organisational principles in primate visual cortical structure. J. Comp. Neurol. 415:33–51, 1999.

Alterations in the phenotype of neocortical pyramidal cells in the Dyrk1A+/- mouse

The gene encoding the dual-specificity tyrosine-regulated kinase DYRK1A maps to the chromosomal segment HSA21q22.2, which lies within the Down syndrome critical region. The reduction in brain size and behavioral defects observed in mice lacking one copy of the murine homologue Dyrk1A (Dyrk1A+/-) support the idea that this kinase may be involved in monosomy 21 associated mental retardation. However, the structural basis of these behavioral defects remains unclear. In the present work, we have analyzed the microstructure of cortical circuitry in the Dyrk1A+/- mouse and control littermates by intracellular injection of Lucifer Yellow in fixed cortical tissue. We found that labeled pyramidal cells were considerably smaller, less branched and less spinous in the cortex of Dyrk1A+/- mice than in control littermates. These results suggest that Dyrk1A influences the size and complexity of pyramidal cells, and thus their capability to integrate information.

The second visual area in the marmoset monkey: visuotopic organisation, magnification factors, architectonical boundaries, and modularity.

The organisation of the second visual area (V2) in marmoset monkeys was studied by means of extracellular recordings of responses to visual stimulation and examination of myelin‐ and cytochrome oxidase‐stained sections. Area V2 forms a continuous cortical belt of variable width (1–2 mm adjacent to the foveal representation of V1, and 3–3.5 mm near the midline and on the tentorial surface) bordering V1 on the lateral, dorsal, medial, and tentorial surfaces of the occipital lobe. The total surface area of V2 is approximately 100 mm2, or about 50% of the surface area of V1 in the same individuals. In each hemisphere, the receptive fields of V2 neurones cover the entire contralateral visual hemifield, forming an ordered visuotopic representation. As in other simians, the dorsal and ventral halves of V2 represent the lower and upper contralateral quadrants, respectively, with little invasion of the ipsilateral hemifield. The representation of the vertical meridian forms the caudal border of V2, with V1, whereas a field discontinuity approximately coincident with the horizontal meridian forms the rostral border of V2, with other visually responsive areas. The bridge of cortex connecting dorsal and ventral V2 contains neurones with receptive fields centred within 1° of the centre of the fovea. The visuotopy, size, shape and location of V2 show little variation among individuals. Analysis of cortical magnification factor (CMF) revealed that the V2 map of the visual field is highly anisotropic: for any given eccentricity, the CMF is approximately twice as large in the dimension parallel to the V1/V2 border as it is perpendicular to this border. Moreover, comparison of V2 and V1 in the same individuals demonstrated that the representation of the central visual field is emphasised in V2, relative to V1. Approximately half of the surface area of V2 is dedicated to the representation of the central 5° of the visual field. Calculations based on the CMF, receptive field scatter, and receptive field size revealed that the point‐image size measured parallel to the V1/V2 border (2–3 mm) equals the width of a full cycle of cytochrome oxidase stripes in V2, suggesting a close correspondence between physiological and anatomical estimates of the dimensions of modular components in this area. J. Comp. Neurol. 387:547–567, 1997.

Spine distribution in cortical pyramidal cells: a common organizational principle across species.

Publisher Summary The chapter discusses the distribution of spines in the dendritic arbors of neocortical pyramidal cells. Several different spine types are illustrated on the apical dendrite of a cortical pyramidal cell. Subsequent classification included pedunculated and sessile spine types. There are marked differences in the density and number of spines in the dendritic arbors of cortical pyramidal cells in different cortical areas. Despite these differences, their normalized cumulative distribution is remarkably constant. The constancy in normalized spine distribution holds true for cortical pyramidal cells in primates, rodents, and monotremes. Environment enrichment, manipulation of inputs and aging do not grossly affect the normalized distribution of spines in the dendritic arbors of cortical pyramidal cells. Spine distribution in cortical pyramidal cells is likely to be determined by epigenetic activity-dependent mechanisms. The most probable activity-dependent mechanism appears to be the backpropagating potential.