Cortex, cognition and the cell: New insights into the pyramidal neuron and prefrontal function

Arguably the most complex conical functions are seated in human cognition, the how and why of which have been debated for centuries by theologians, philosophers and scientists alike. In his best-selling book, An Astonishing Hypothesis: A Scientific Search for the Soul, Francis Crick refined the view that these qualities are determined solely by cortical cells and circuitry. Put simply, cognition is nothing more, or less, than a biological function. Accepting this to be the case, it should be possible to identify the mechanisms that subserve cognitive processing. Since the pioneering studies of Lorent de No and Hebb, and the more recent studies of Fuster, Miller and Goldman-Rakic, to mention but a few, much attention has been focused on the role of persistent neural activity in cognitive processes. Application of modern technologies and modelling techniques has led to new hypotheses about the mechanisms of persistent activity. Here I focus on how regional variations in the pyramidal cell phenotype may determine the complexity of cortical circuitry and, in turn, influence neural activity. Data obtained from thousands of individually injected pyramidal cells in sensory, motor, association and executive cortex reveal marked differences in the numbers of putative excitatory inputs received by these cells. Pyramidal cells in prefrontal cortex have, on average, up to 23 times more dendritic spines than those in the primary visual area. I propose that without these specializations in the structure of pyramidal cells, and the circuits they form, human cognitive processing would not have evolved to its present state. I also present data from both New World and Old World monkeys that show varying degrees of complexity in the pyramidal cell phenotype in their prefrontal cortices, suggesting that cortical circuitry and, thus, cognitive styles are evolving independently in different species.

Linear models of simple cells: Correspondence to real cell responses and space spanning properties

Despite their limitations, linear filter models continue to be used to simulate the receptive field properties of cortical simple cells. For theoreticians interested in large scale models of visual cortex, a family of self-similar filters represents a convenient way in which to characterise simple cells in one basic model. This paper reviews research on the suitability of such models, and goes on to advance biologically motivated reasons for adopting a particular group of models in preference to all others. In particular, the paper describes why the Gabor model, so often used in network simulations, should be dropped in favour of a Cauchy model, both on the grounds of frequency response and mutual filter orthogonality.

Color constancy and the functional significance of McCollough effects

A central problem in visual perception concerns how humans perceive stable and uniform object colors despite variable lighting conditions (i.e. color constancy). One solution is to 'discount' variations in lighting across object surfaces by encoding color contrasts, and utilize this information to 'fill in' properties of the entire object surface. Implicit in this solution is the caveat that the color contrasts defining object boundaries must be distinguished from the spurious color fringes that occur naturally along luminance-defined edges in the retinal image (i.e. optical chromatic aberration). In the present paper, we propose that the neural machinery underlying color constancy is complemented by an 'error-correction' procedure which compensates for chromatic aberration, and suggest that error-correction may be linked functionally to the experimentally induced illusory colored aftereffects known as McCollough effects (MEs). To test these proposals, we develop a neural network model which incorporates many of the receptive-field (RF) profiles of neurons in primate color vision. The model is composed of two parallel processing streams which encode complementary sets of stimulus features: one stream encodes color contrasts to facilitate filling-in and color constancy; the other stream selectively encodes (spurious) color fringes at luminance boundaries, and learns to inhibit the filling-in of these colors within the first stream. Computer simulations of the model illustrate how complementary color-spatial interactions between error-correction and filling-in operations (a) facilitate color constancy, (b) reveal functional links between color constancy and the ME, and (c) reconcile previously reported anomalies in the local (edge) and global (spreading) properties of the ME. We discuss the broader implications of these findings by considering the complementary functional roles performed by RFs mediating color-spatial interactions in the primate visual system. (C) 2002 Elsevier Science Ltd. All rights reserved.

Spreading and synchronization of intrinsic signals in visual cortex of macaque monkey evoked by a localized visual stimulus

Spatio-temporal maps of the occipital cortex of macaque monkeys were analyzed using optical imaging of intrinsic signals. The images obtained during localized visual stimulation (IS) were compared with the images obtained on presentation of a blank screen (IB). We first investigated spontaneous variations of the intrinsic signals by analyzing the 100 IBs for each of the three cortical areas. Slow periodical activation was observed in alternation over the cortical areas. Cross-correlation analysis indicated that synchronization of spontaneous activation only took place within each cortical area, but not between them. When a small, drifting grating (2degreesX2degrees) was presented on the fovea. a dark spot appeared in the optical image at the cortical representation of this retinal location. It spread bilaterally along the border between V1 and V2, continuing as a number of parallel dark bands covering a large area of the lateral surface of V1. Cross-correlation analysis showed that during visual stimulation the intrinsic signals over all of the three cortical areas were synchronized, with in-phase activation of V1 and V2 and anti-phase activation of V4 and V1/V2. The significance of these extensive synergistic and antagonistic interactions between different cortical areas is discussed. (C) 2003 Elsevier B.V. All rights reserved.

Topographic plasticity in primary visual cortex is mediated by local corticocortical connections

The placement of monocular laser lesions in the adult cat retina produces a lesion projection zone (LPZ) in primary visual cortex (V1) in which the majority of neurons have a normally located receptive field (RF) for stimulation of the intact eye and an ectopically located RF ( displaced to intact retina at the edge of the lesion) for stimulation of the lesioned eye. Animals that had such lesions for 14 - 85 d were studied under halothane and nitrous oxide anesthesia with conventional neurophysiological recording techniques and stimulation of moving light bars. Previous work suggested that a candidate source of input, which could account for the development of the ectopic RFs, was long-range horizontal connections within V1. The critical contribution of such input was examined by placing a pipette containing the neurotoxin kainic acid at a site in the normal V1 visual representation that overlapped with the ectopic RF recorded at a site within the LPZ. Continuation of well defined responses to stimulation of the intact eye served as a control against direct effects of the kainic acid at the LPZ recording site. In six of seven cases examined, kainic acid deactivation of neurons at the injection site blocked responsiveness to lesioned-eye stimulation at the ectopic RF for the LPZ recording site. We therefore conclude that long-range horizontal projections contribute to the dominant input underlying the capacity for retinal lesion-induced plasticity in V1.

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. Copyright (C) 2005 S. Karger AG, Basel.

Local edge detectors: A substrate for fine spatial vision at low temporal frequencies in rabbit retina

Visual acuity is limited by the size and density of the smallest retinal ganglion cells, which correspond to the midget ganglion cells in primate retina and the beta- ganglion cells in cat retina, both of which have concentric receptive fields that respond at either light- On or light- Off. In contrast, the smallest ganglion cells in the rabbit retina are the local edge detectors ( LEDs), which respond to spot illumination at both light- On and light- Off. However, the LEDs do not predominate in the rabbit retina and the question arises, what role do they play in fine spatial vision? We studied the morphology and physiology of LEDs in the isolated rabbit retina and examined how their response properties are shaped by the excitatory and inhibitory inputs. Although the LEDs comprise only similar to 15% of the ganglion cells, neighboring LEDs are separated by 30 - 40 mu m on the visual streak, which is sufficient to account for the grating acuity of the rabbit. The spatial and temporal receptive- field properties of LEDs are generated by distinct inhibitory mechanisms. The strong inhibitory surround acts presynaptically to suppress both the excitation and the inhibition elicited by center stimulation. The temporal properties, characterized by sluggish onset, sustained firing, and low bandwidth, are mediated by the temporal properties of the bipolar cells and by postsynaptic interactions between the excitatory and inhibitory inputs. We propose that the LEDs signal fine spatial detail during visual fixation, when high temporal frequencies are minimal.

Nutritional effects on neuron numbers

Undemutrition during early life is known to cause deficits and distortions of brain structure although it has remained uncertain whether or not this includes a diminution of the total numbers of neurons. Estimates of numerical density (e.g. number of cells per microscopic field, or number of cells per unit area of section, or number of cells per unit volume of tissue) are extremely difficult to interpret and do not provide estimates of total numbers of cells. However, advances in stereological techniques have made it possible to obtain unbiased estimates of total numbers of cells in well defined biological structures. These methods have been utilised in studies to determine the effects of varying periods of undernutrition during early life on the numbers of neurons in various regions of the rat brain. The regions examined so far have included the cerebellum, the dentate gyrus, the olfactory bulbs and the cerebral cortex. The only region to show, unequivocally, that a period of undernutrition during early life causes a deficit in the number of neurons was the dentate gyrus. These findings are discussed in the context of other morphological and functional deficits present in undernourished animals.

The use of transcriptional profiles to predict adult mosquito age under field conditions

Age is a critical determinant of an adult female mosquito's ability to transmit a range of human pathogens. Despite its central importance, relatively few methods exist with which to accurately determine chronological age of field-caught mosquitoes. This fact is a major constraint on our ability to fully understand the relative importance of vector longevity to disease transmission in different ecological contexts. It also limits our ability to evaluate novel disease control strategies that specifically target mosquito longevity. We report the development of a transcriptional profiling approach to determine age of adult female Aedes aegypti under field conditions. We demonstrate that this approach surpasses current cuticular hydrocarbon methods for both accuracy of predicted age as well as the upper limits at which age can be reliably predicted. The method is based on genes that display age-dependent expression in a range of dipteran insects and, as such, is likely to be broadly applicable to other disease vectors.

Reliability and validity of physical fitness field tests for adults aged 55 to 70 years

The aim of this study was to examine the reliability and validity of field tests for assessing physical function in mid-aged and young-old people (55–70 y). Tests were selected that required minimal space and equipment and could be implemented in multiple field settings such as a general practitioner's office. Nineteen participants completed 2 field and 1 laboratory testing sessions. Intra-class correlations showed good reliability for the tests of upper body strength (lift and reach, R= .66), lower body strength (sit to stand, R= .80) and functional capacity (Canadian Step Test, R= .92), but not for leg power (single timed chair rise, R= .28). There was also good reliability for the balance test during 3 stances: parallel (94.7% agreement), semi-tandem (73.7%), and tandem (52.6%). Comparison of field test results with objective laboratory measures found good validity for the sit to stand (cf 1RM leg press, Pearson r= .68, p< .05), and for the step test (cf PWC140, r= −.60, p< .001), but not for the lift and reach (cf 1RM bench press, r= .43, p> .05), balance (r= −.13, −.18, .23) and rate of force development tests (r= −.28). It was concluded that the lower body strength and cardiovascular function tests were appropriate for use in field settings with mid-aged and young-old adults.

Host age effect and expression of cytoplasmic incompatibility in field populations of Wolbachia-superinfected Aedes albopictus

The Asian tiger mosquito, Aedes albopictus (Skuse), is a known vector of dengue in South America and Southeast Asia. It is naturally superinfected with two strains of Wolbachia endosymbiont that are able to induce cytoplasmic incompatibility (CI). In this paper, we report the strength of CI expression in crosses involving field-caught males. CI expression was found to be very strong in all crosses between field males and laboratory-reared uninfected or wAlbA infected young females. In addition, crossing experiments with laboratory colonies showed that aged super- infected males could express strong CI when mated with young uninfected or wAlbA infected females. These results provide additional evidence that the CI properties of Wolbachia infecting Aedes albopictus are well suited for applied strategies that seek to utilise Wolbachia for host population modification.

Field prevalence of Wolbachia in the mosquito vector Aedes albopictus

The endosymbiotic bacteria in the genus Wolbachia have been proposed as a potential candidate to deliver pathogen-blocking genes into natural populations of medically important insects. The successful application of Wolbachia in insect vector control depends on the ability of the agent to successfully invade and maintain itself at high frequency under field conditions. Here, we evaluated the prevalence of Wolbachia infections in a field population of the Wolbachia-superinfected mosquito Aedes albopictus. A field prevalence of 100% (n = 1,016) was found in a single population in eastern Thailand via polymerase chain reaction (PCR) testing of Wolbachia both from individual parent females and their corresponding F1 offspring. This is the first report of accurate Wolbachia prevalence in a field population of an insect disease vector. The prevalence of superinfection was estimated to be 99.41%. All single-infected individual mosquitoes (n = 6) were found to harbor group A Wolbachia. For this particular population, none was found to be single-infected with group B Wolbachia. Our results also show that PCR testing of field materials alone without checking F1 offspring overestimated the natural prevalence of single infection. Thus, the confirmation of infection status by means of F1 offspring was critical to the accurate estimates of Wolbachia prevalence under field conditions.

Determination of Wolbachia genome size by Pulsed-Field Gel Electrophoresis

Genome sizes of six different Wolbachia strains from insect and nematode hosts have been determined by pulsed-field gel electrophoresis of purified DNA both before and after digestion with rare-cutting restriction endonucleases. Enzymes SmaI, ApaI, AscI, and FseI cleaved the studied Wolbachia strains at a small number of sites and were used for the determination of the genome sizes of wMelPop, wMel, and wMelCS (each 1.36 Mb), wRi (1.66 Mb), wBma (1.1 Mb), and wDim (0.95 Mb). The Wolbachia genomes studied were all much smaller than the genomes of free-living bacteria such as Escherichia coli (4.7 Mb), as is typical for obligate intracellular bacteria. There was considerable genome size variability among Wolbachia strains, especially between the more parasitic A group Wolbachia infections of insects and the mutualistic C and D group infections of nematodes. The studies described here found no evidence for extrachromosomal plasmid DNA in any of the strains examined. They also indicated that the Wolbachia genome is circular.

Extending teaching and learning initiatives in the cross-disciplinary field of biotechnology

Our AUTC Biotechnology study (Phases 1 and 2) identified a range of areas that could benefit from a common approach by universities nationally. A national network of biotechnology educators needs to be solidified through more regular communication, biennial meetings, and development of methods for sharing effective teaching practices and industry placement strategies, for example. Our aims in this proposed study are to: a. Revisit the state of undergraduate biotechnology degree programs nationally to determine their rate of change in content, growth or shrinkage in student numbers (as the biotech industry has had its ups and downs in recent years), and sustainability within their institutions in light of career movements of key personnel, tightening budgets, and governmental funding priorities. b. Explore the feasibility of a range of initiatives to benefit university biotechnology education to determine factors such as how practical each one is, how much buy-in could be gained from potentially participating universities and industry counterparts, and how sustainable such efforts are. One of many such initiatives arising in our AUTC Biotech study was a national register of industry placements for final-year students. c. During scoping and feasibility study, to involve our colleagues who are teaching in biotechnology – and contributing disciplines. Their involvement is meant to yield not only meaningful insight into how to strengthen biotechnology teaching and learning but also to generate ‘buy-in’ on any initiatives that result from this effort.