动物数能力的研究进展

动物数能力(numerical competence)是比较心理学、认知心理学和认知神经科学研究的热点之一。研究表明：(1)动物具有相对数量判断能力(relative numerousness judgments)和数量顿识能力(subitizing);(2)动物是否具有计数能力(counting)尚存在争议;(3)动物没有数量估算能力(estimation)。神经生理学研究发现,猴的后顶叶和前额叶在数功能方面扮演重要角色。     

Numerical processing: stimulating numbers

A new study using transcranial direct current stimulation shows that modulating parietal cortex activity during the learning of abstract numerical material can enhance numerical competency for up to six months.     

An Eulerian/XFEM formulation for the large deformation of cortical cell membrane

Most animal cells are surrounded by a thin layer of actin meshwork below their membrane, commonly known as the actin cortex (or cortical membrane). An increasing number of studies have highlighted the role of this structure in many cell functions including contraction and locomotion, but modelling has been limited by the fact that the membrane thickness (about 1?μm) is usually much smaller than the typical size of a cell (10-100?μm). To overcome theoretical and numerical issues resulting from this observation, we introduce in this paper a continuum formulation, based on surface elasticity, that views the cortex as an infinitely thin membrane that can resists tangential deformation. To accurately model the large deformations of cells, we introduced equilibrium equations and constitutive relations within the Eulerian viewpoint such that all quantities (stress, rate of deformation) lie in the current configuration. A solution procedure is then introduced based on a coupled extended finite element approach that enables a continuum solution to the boundary value problem in which discontinuities in both strain and displacement (due to cortical elasticity) are easily handled. We validate the approach by studying the effect of cortical elasticity on the deformation of a cell adhering on a stiff substrate and undergoing internal contraction. Results show very good prediction of the proposed method when compared with experimental observations and analytical solutions for simple cases. In particular, the model can be used to study how cell properties such as stiffness and contraction of both cytoskeleton and cortical membrane lead to variations in cell's surface curvature. These numerical results show that the proposed method can be used to gain critical insights into how the cortical membrane affects cell deformation and how it may be used as a means to determine a cell's mechanical properties by measuring curvatures of its membrane.     

A mathematical model of the primary visual cortex and hypercolumn

A mathematical model of the primary visual cortex is presented. Basically, the model comprises two features. Firstly, in analogy with the principle of the computerized tomography (CT), it assumes that simple cells in each hypercolumn are not merely detecting line segments in images as features, but rather that they are as a whole representing the local image with a certain representation. Secondly, it assumes that each hypercolumn is performing spatial frequency analyses of local images using that representation, and that the resultant spectra are represented by complex cells. The model is analyzed using numerical simulations and its advantages are discussed from the viewpoint of visual information processing. It is shown that 1) the proposed processing is tolerant to shifts in position of input images, and that 2) spatial frequency filtering operations can be easily performed in the model.     

The cost of cortical computation

Electrophysiological recordings show that individual neurons in cortex are strongly activated when engaged in appropriate tasks, but they tell us little about how many neurons might be engaged by a task, which is important to know if we are to understand how cortex encodes information. For human cortex, I estimate the cost of individual spikes, then, from the known energy consumption of cortex, I establish how many neurons can be active concurrently. The cost of a single spike is high, and this severely limits, possibly to fewer than 1%, the number of neurons that can be substantially active concurrently. The high cost of spikes requires the brain not only to use representational codes that rely on very few active neurons, but also to allocate its energy resources flexibly among cortical regions according to task demand. The latter constraint explains the investment in local control of hemodynamics, exploited by functional magnetic resonance imaging, and the need for mechanisms of selective attention.     

A computational model of ameboid deformation and locomotion

Traditional continuum models of ameboid deformation and locomotion are limited by the computational difficulties intrinsic in free boundary conditions. A new model using the immersed boundary method overcomes these difficulties by representing the cell as a force field immersed in fluid domain. The forces can be derived from a direct mechanical interpretation of such cell components as the cell membrane, the actin cortex, and the transmembrane adhesions between the cytoskeleton and the substratum. The numerical cytoskeleton, modeled as a dynamic network of immersed springs, is able to qualitatively model the passive mechanical behavior of a shear-thinning viscoelastic fluid (Bottino 1997). The same network is used to generate active protrusive and contractile forces. When coordinated with the attachment-detachment cycle of the cell's adhesions to the substratum, these forces produce directed locomotion of the model ameba. With this model it is possible to study the effects of altering the numerical parameters upon the motility of the model cell in a manner suggestive of genetic deletion experiments. In the context of this ameboid cell model and its numerical implementation, simulations involving multicellular interaction, detailed internal signaling, and complex substrate geometries are tractable. Received: 5 January 1998 / Revised version: 23 March 1998 / Accepted: 26 March 1998     

Mechanics of the cellular actin cortex: From signalling to shape change

The actin cortex is a thin layer of actin, myosin and actin-binding proteins that underlies the membrane of most animal cells. It is highly dynamic and can undergo remodelling on timescales of tens of seconds, thanks to protein turnover and myosin-mediated contractions. The cortex enables cells to resist external mechanical stresses, controls cell shape and allows cells to exert forces on their neighbours. Thus, its mechanical properties are the key to its physiological function. Here, we give an overview of how cortex composition, structure and dynamics control cortex mechanics and cell shape. We use mitosis as an example to illustrate how global and local regulation of cortex mechanics gives rise to a complex series of cell shape changes.     

In vitro studies of peptidoglycan binding and hydrolysis by the Bacillus anthracis germination-specific lytic enzyme SleB

The Bacillus anthracis endospore loses resistance properties during germination when its cortex peptidoglycan is degraded by germination-specific lytic enzymes (GSLEs). Although this event normally employs several GSLEs for complete cortex removal, the SleB protein alone can facilitate enough cortex hydrolysis to produce vulnerable spores. As a means to better understand its enzymatic function, SleB was overexpressed, purified, and tested in vitro for depolymerization of cortex by measurement of optical density loss and the solubilization of substrate. Its ability to bind peptidoglycan was also investigated. SleB functions independently as a lytic transglycosylase on both intact and fragmented cortex. Most of the muropeptide products that SleB generates are large and are potential substrates for other GSLEs present in the spore. Study of a truncated protein revealed that SleB has two domains. The N-terminal domain is required for stable peptidoglycan binding, while the C-terminal domain is the region of peptidoglycan hydrolytic activity. The C-terminal domain also exhibits dependence on cortex containing muramic-δ-lactam in order to carry out hydrolysis. As the conditions and limitations for SleB activity are further elucidated, they will enable the development of treatments that stimulate premature germination of B. anthracis spores, greatly simplifying decontamination measures.     

Mechanisms of cortical electrical activity and emergence of gamma rhythm

A continuum model of the electrical activity of the cerebral cortex is described which predicts the occurrence of a resonance in the gamma range near 40 Hz. The emergence of this resonance is due to two refinements to a previous model, namely the inclusion of a modulation of synaptic strength due to finite reversal potentials, and use of parameters that better match physiological measurements. Analytical expressions for the fixed points of the system and for its linear dynamics are found in terms of average neuronal properties, and together explain the occurrence and modulation of the gamma-like resonance. The analytical results are confirmed by a numerical simulation.     

Determination of the fraction of active inputs required by a neuron to fire

What fraction of the inputs to a neuron in the primary visual cortex (V1) need to be active for that neuron to reach its firing threshold? The paper describes a numerical method for estimating the selectivity of visual neurons, in terms of the required fraction of active excitatory inputs, from standard data produced by intracellular electro-physiological recordings. The method also provides an estimate of the relative strength of the feedforward inhibition in a push-pull model of the inputs to V1 simple cells. The method is tested on two V1 cells described in Carandini and Ferster [Carandini, M., Ferster, D., 2000. Membrane potential and firing rate in cat primary visual cortex. J. Neurosci. 20, 470-484]. The results indicate that the maximum strength of feedforward inhibition is around 30% of the maximum strength of feedforward excitation. The two V1 neurons investigated fire if more than around 40% of their excitatory LGN inputs are active.     

Adaptive bone-remodeling theory applied to prosthetic-design analysis

The subject of this article is the development and application of computer-simulation methods to predict stress-related adaptive bone remodeling, in accordance with 'Wolff's Law'. These models are based on the Finite Element Method (FEM) in combination with numerical formulations of adaptive bone-remodeling theories. In the adaptive remodeling models presented, the Strain Energy Density (SED) is used as a feed-back control variable to determine shape or bone density adaptations to alternative functional requirements, whereby homeostatic SED distribution is assumed as the remodeling objective. These models are applied to investigate the relation between 'stress shielding' and bone resorption in the femoral cortex around intramedullary prostheses, such as used in Total Hip Arthroplasty (THA). It is shown that the amount of bone resorption depends mainly on the rigidity and the bonding characteristics of the implant. Homeostatic SED can be obtained when the resorption process occurs at the periosteal surface, rather than inside the cortex, provided that the stem is adequately flexible.     

Extracting Wave Structure from Biological Data with Application to Responses in Turtle Visual Cortex

Waves have long been thought to be a fundamental mechanism for communicating information within a medium and are widely observed in biological systems. However, a quantitative analysis of biological waves is confounded by the variability and complexity of the response. This paper proposes a robust technique for extracting wave structure from experimental data by calculating "wave subspaces" from the KL decomposition of the data set. If a wave subspace contains a substantial portion of the data set energy during a particular time interval, one can deduce the structure of the wave and potentially isolate its information content. This paper uses the wave subspace technique to extract and compare wave structure in data from three different preparations of the turtle visual cortex. The paper demonstrates that wave subspace caricatures from the three cortical preparations have qualitative similarities. In the numerical model, where information about the underlying dynamics is available, wave subspace landmarks are related to activation and changes in behavior of other dynamic variables besides membrane potential.     

RhoA- and Cdc42-induced antagonistic forces underlie symmetry breaking and spindle rotation in mouse oocytes

Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and 2 small polar bodies. This relies on the ability of the cell to break symmetry and position its spindle close to the cortex before anaphase occurs. In metaphase II–arrested mouse oocytes, the spindle is actively maintained close and parallel to the cortex, until fertilization triggers sister chromatid segregation and the rotation of the spindle. The latter must indeed reorient perpendicular to the cortex to enable cytokinesis ring closure at the base of the polar body. However, the mechanisms underlying symmetry breaking and spindle rotation have remained elusive. In this study, we show that spindle rotation results from 2 antagonistic forces. First, an inward contraction of the cytokinesis furrow dependent on RhoA signaling, and second, an outward attraction exerted on both sets of chromatids by a Ran/Cdc42-dependent polarization of the actomyosin cortex. By combining live segmentation and tracking with numerical modeling, we demonstrate that this configuration becomes unstable as the ingression progresses. This leads to spontaneous symmetry breaking, which implies that neither the rotation direction nor the set of chromatids that eventually gets discarded are biologically predetermined.

Mammalian oocyte meiotic divisions are highly asymmetric and produce a large haploid gamete and two small polar bodies, but the mechanisms underlying the required symmetry breaking and spindle rotation have remained elusive. This study shows that spindle rotation in activated mouse oocytes relies on spontaneous symmetry breaking resulting from an unstable configuration generated by cleavage furrow ingression and cortical chromosome attraction.     

The anatomy of the cerebral cortex of the echidna (Tachyglossus aculeatus)

The cerebral cortex of the echidna is notable for its extensive folding and the positioning of major functional areas towards its caudal extremity. The gyrification of the echidna cortex is comparable in magnitude to prosimians and cortical thickness and neuronal density are similar to that seen in rodents and carnivores. On the other hand, many pyramidal neurons in the cerebral cortex of the echidna are atypical with inverted somata and short or branching apical dendrites. All other broad classes of neurons noted in therian cortex are also present in the echidna, suggesting that the major classes of cortical neurons evolved prior to the divergence of proto- and eutherian lineages. Dendritic spine density on dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons is lower than that found in eutheria. On the other hand, synaptic morphology, density and distribution in somatosensory cortex are similar to that in eutheria. In summary, although the echidna cerebral cortex displays some structural features, which may limit its functional capacities (e.g. lower spine density on pyramidal neurons), in most structural parameters (e.g. gyrification, cortical area and thickness, neuronal density and types, synaptic morphology and density), it is comparable to eutheria.     

The number domain- can we count on parietal cortex?

Does the primate brain contain a dedicated and localized neural circuitry for processing generic numerical information? The human parietal cortex, particularly the intraparietal sulcus (IPS), has long been implicated in processing symbolic (verbal) number information. If the IPS is indeed the site of generic numerical processing, however, its neurons should also encode nonsymbolic numerosity information. Two recent studies by Shuman and Kanwisher and by Piazza et al. published in this issue of Neuron tested this assumption...with quite different results.     

Dopamine D1-stimulated adenylyl cyclase activity in cerebral cortex of autopsied human brain.

Although the cerebral cortical dopamine D(1) receptor is considered to play a role in normal and abnormal brain function, little information is available on its characteristics in human brain. We compared dopamine-stimulated adenylyl cyclase (AC) activity in homogenates of cerebral cortex (frontal, temporal, parietal, occipital and cingulate cortex) of autopsied brain of neurologically normal subjects to that in striatum. Cerebral cortical AC activity was modestly and dose-dependently stimulated by dopamine (maximal 20-30%) with low microM EC50s and such stimulation was inhibited by the selective dopamine D1 receptor antagonist SCH23390. The magnitude of the maximal stimulation by dopamine was similar in autopsied and biopsied cerebral cortex. The extent of maximal stimulation was similar to that in dopamine-rich striatum (caudate, putamen and nucleus accumbens), despite much lower density of dopamine D1 receptors in cerebral cortex vs. striatum. The EC50 for dopamine stimulation in cerebral cortex (approximately 1 microM) was lower than that for caudate and putamen (approximately 3 microM). No detectable dopamine stimulation was observed in cerebellar cortex, thalamus or hippocampus. Dopamine stimulation in both cerebral cortex and striatum was independent of calcium activation. We conclude that dopamine stimulated AC can be measured in cerebral cortex of human brain allowing for the possibility that this process can be examined in human brain disorders in which dopaminergic abnormalities are suspected.     

Motor cortex plasticity--from physiology to clinical neurology.

Neurophysiologic, neuroanatomic and neuroimaging studies conducted over the past two decades reveal that the cerebral cortex is functionally and structurally dynamic. The functional topography of the motor cortex can be modified by a variety of experimental manipulations, including peripheral or central injury, electrical stimulation, pharmocologic treatment or behavioral experience. Recent evidence demonstrates that functional alterations in motor cortex organization are accompanied by changes in dendritic and synaptic structure, as well as alterations in the regulation of cortical neurotransmitter systems. This article describes the state of the science regarding the main mechanisms implicated in the motor cortex plasticity, the main tools used for its investigation and the consequence of the recent discoveries on the therapeutic and rehabilitation procedures for the brain-injured persons.     

A radial glia-specific role of RhoA in double cortex formation

The positioning of neurons in the cerebral cortex is of crucial importance for its function as highlighted by the severe consequences of migrational disorders in patients. Here we show that genetic deletion of the small GTPase RhoA in the developing cerebral cortex results in two migrational disorders: subcortical band heterotopia (SBH), a heterotopic cortex underlying the normotopic cortex, and cobblestone lissencephaly, in which neurons protrude beyond layer I at the pial surface of the brain. Surprisingly, RhoA(-/-) neurons migrated normally when transplanted into wild-type cerebral cortex, whereas the converse was not the case. Alterations in the radial glia scaffold are demonstrated to cause these migrational defects through destabilization of both the actin and the microtubules cytoskeleton. These data not only demonstrate that RhoA is largely dispensable for migration in neurons but also showed that defects in radial glial cells, rather than neurons, can be sufficient to produce SBH.     

A model of feedback control for the charge-balanced suppression of epileptic seizures

Here we present several refinements to a model of feedback control for the suppression of epileptic seizures. We utilize a stochastic partial differential equation (SPDE) model of the human cortex. First, we verify the strong convergence of numerical solutions to this model, paying special attention to the sharp spatial changes that occur at electrode edges. This allows us to choose appropriate step sizes for our simulations; because the spatial step size must be small relative to the size of an electrode in order to resolve its electrical behavior, we are able to include a more detailed electrode profile in the simulation. Then, based on evidence that the mean soma potential is not the variable most closely related to the measurement of a cortical surface electrode, we develop a new model for this. The model is based on the currents flowing in the cortex and is used for a simulation of feedback control. The simulation utilizes a new control algorithm incorporating the total integral of the applied electrical potential. Not only does this succeed in suppressing the seizure-like oscillations, but it guarantees that the applied signal will be charge-balanced and therefore unlikely to cause cortical damage.     

CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta

CLASPs are mammalian microtubule-stabilizing proteins that can mediate the interaction between distal microtubule ends and the cell cortex. Using mass spectrometry-based assays, we have identified two CLASP partners, LL5beta and ELKS. LL5beta and ELKS form a complex that colocalizes with CLASPs at the cortex of HeLa cells as well as at the leading edge of motile fibroblasts. LL5beta is required for cortical CLASP accumulation and microtubule stabilization in HeLa cells, while ELKS plays an accessory role in these processes. LL5beta is a phosphatidylinositol-3,4,5-triphosphate (PIP3) binding protein, and its recruitment to the cell cortex is influenced by PI3 kinase activity but does not require intact microtubules. Cortical clusters of LL5beta and ELKS do not overlap with focal adhesions but often form in their vicinity and can affect their size. We propose that LL5beta and ELKS can form a PIP3-regulated cortical platform to which CLASPs attach distal microtubule ends.