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Spatial cognitive maps in animals: new hypotheses on their structure and neural mechanisms.

This article provides a hierarchical model of animal spatial cognitive maps. Such maps include both topological information, which affords loose, yet operational, representations of the connectivity of space and its overall arrangement, and metric information, which provides information about angles and distances. The model holds that maps can be initially described as a set of location-dependent reference frameworks providing directional information about other locations. The addition of an overall directional reference allows for the buildup of more complete (allocentric) representations. A survey of recent neurobiological data provides some hints about the brain structures involved in these processes and suggests that the hippocampal formation and the posterior parietal cortex would act differently by handling topological and metric information, respectively.

Animals↗

Location of a protease-hypersensitive region in the multidrug resistance protein (MRP) by mapping of the epitope of MRP-specific monoclonal antibody QCRL-1.

Multidrug resistance protein (MRP) is a Mr 190,000 integral membrane phosphoglycoprotein which has been shown by transfection studies to confer multidrug resistance. We have previously raised and characterized a panel of MRP-specific monoclonal antibodies (MAbs) which detect distinct epitopes in the MRP molecule (D. R. Hipfner et A, Cancer Res., 54. 5788-5792, 1994), and, in the present study, we have identified the epitope of one of these, MAb QCRL-1. Immunoblot analysis of MRP fragments generated by digestion with formic acid or trypsin suggested that the MAb QCRL-1 epitope was located in the region connecting the two halves of MRP. Subsequent analyses of a series of truncated bacterial glutathione S-transferase fusion proteins containing segments of human MRP further localized the MAb QCRL-1 epitope to a region encompassing amino acids 903-956. Similar experiments with an analogous segment of murine MRP demonstrated that MAb QCRL-1 was highly specific for the human protein. The reactivity of MAb QCRL-1 with a series of overlapping hexapeptides and heptapeptides within this region identified the human MRP-specific heptapeptide SSYSGDI (corresponding to amino acids 918-924) as the epitope, and this peptide was shown to specifically inhibit MAb QCRL-1 binding to MRP. The results of these studies confirm that this epitope has a cytoplasmic location consistent with the topology of MRP predicted from hydrophobicity analyses. These experiments also revealed the presence of a number of protease-sensitive sites on either side of the MAb QCRL-1 epitope in the cytoplasmic domain connecting the two halves of MRP. Future epitope-mapping studies with other MRP-specific MAbs win provide additional insights into the topology of MRP, and may help to identify functionally important regions of this protein. Moreover, definition of the epitope recognized by MAb QCRL-1 as well as the other MAbs will facilitate the use of these reagents for immunohistological studies of MRP expression in drug-resistant tumors.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

[Genetic relationship of the loci of phosphohexose isomerase and G-system blood groups in swine].

The hybridological analysis for gene mapping of the locus of phosphohexose isomerase (PHI) of pigs was carried out. The locus of G blood group system was used as a marker of the chromosome 15. 26 families with 200 piglets were obtained from backcross matings. The analysis of haplotype segregation pointed to the lack of independent inheritance of PHI and G systems loci and to weak linkage between these loci. The recombination frequency was estimated to be 39%. The results obtained are discussed in connection with the problem of establishment of accurate gene maps.

Animals↗

Anatomical evidence for somatotopic maps in the zona incerta of rats.

We explore the patterns of connectivity between the zona incerta (ZI) and major centres of the somatosensory system in rats. Injections of cholera toxin subunit B (CTb) or biotinylated dextran (BD) were made into different somatosensory centres (Par1, FL and HL cortex; principal and spinal trigeminal nuclei; cervical, thoracic and lumbar spinal cord) of rats. Double injections of different coloured fluorescent dextrans (fluororuby and dextran-fluorescein) or BD and CTb (revealed with different chromogens) were also made into adjacent cortical regions (Par1 and FL). After injections into each of these somatosensory centres, a distinctive labelling pattern becomes apparent. Labelled terminals from centres representing the head (Par1, trigeminal nuclei) are found in the medial ZI, while labelled terminals from forelimb (FL, cervical spinal cord), trunk (thoracic cord) and hindlimb (HL, lumbar cord) centres are found in progressively more lateral areas of the nucleus. In general, rich terminal labelling is seen in the ZI after injections into the head and forelimb centres, while very poor labelling is seen after injections into the trunk and hindlimb centres. Our double injections show that adjacent but distinct cortical areas (Par1 and FL) occupy mainly separate territories in the ZI, but with some overlap. After each injection, from the cortex to the spinal cord, only a few labelled cells are seen. Our results indicate anatomical evidence for a somatotopic map within the ZI, with a preferential representation of the head and upper limbs. We suggest that the ZI may function to influence arousal states and orientating movements in relation to particularly active somatosensory inputs.

Animals↗

A second locus for Marfan syndrome maps to chromosome 3p24.2-p25.

Marfan syndrome (MFS) is an autosomal dominant connective-tissue disorder characterized by skeletal, ocular and cardiovascular defects of highly variable expressivity. The diagnosis relies solely on clinical criteria requiring anomalies in at least two systems. By excluding the chromosome 15 disease locus, fibrillin 1 (FBN1), in a large French family with typical cardiovascular and skeletal anomalies, we raised the issue of genetic heterogeneity in MFS and the implication of a second locus (MFS2). Linkage analyses, performed in this family, have localized MFS2 to a region of 9 centiMorgans between D3S1293 and D3S1283, at 3p24.2-p25. In this region, the highest lod score was found with D3S2336, of 4.89 (theta = 0.05). By LINKMAP analyses, the most probable position for the second locus in MFS was at D3S2335.

Adult↗

Motor maps and synergies.

Consider the process of raising and lowering the arm in the sagittal plane. Different parts of different muscles operate over different sectors of the angular range. How and why does the nervous system implement this differential muscle activation according to joint angle? We contend that such control depends on the adaptive formation of motor maps. These solve the problem of redundancy in the musculoskeletal system by connecting a relatively small number of cortical columns in the motor cortex to a large number of alpha motor neuron pools. We argue that motor maps are formed such that each functional muscle is activated in proportion to its moment arm about the movement. Because of this the required agonist and antagonist turning forces are generated with a minimum demand for metabolic energy. We know from biomechanical principles that, at any given posture, those muscle fibres that change length most in response to a small joint-angle change are those with the greatest moment arm. Likewise those that change least have the smallest. By establishing a model of the polynomial relationships between the lengths of functional muscles l and the corresponding changes in joint angles theta, the nervous system can generate signals partial differentiallj/ partial differentialthetai (where lj is the length of the jth functional muscle and thetai is the magnitude of the ith elemental movement). These signals create motor maps by modulating the gains of descending motor pathways. As a result, functional muscles are activated in proportion to their moment arms. This reduces the demand for metabolic energy to a minimum. Since moment arms change with joint angle, it also accounts for the experimental observations above. Such motor mapping effectively provides a minimum energy "wired-in" synergy. Established in utero, motor maps are the first stage of synergy formation and provide the basis for the development of subsequent task-dependent synergies.

Biomechanical Phenomena↗

A comparative evaluation of wavelet-based methods for hypothesis testing of brain activation maps.

Wavelet-based methods for hypothesis testing are described and their potential for activation mapping of human functional magnetic resonance imaging (fMRI) data is investigated. In this approach, we emphasise convergence between methods of wavelet thresholding or shrinkage and the problem of hypothesis testing in both classical and Bayesian contexts. Specifically, our interest will be focused on the trade-off between type I probability error control and power dissipation, estimated by the area under the ROC curve. We describe a technique for controlling the false discovery rate at an arbitrary level of error in testing multiple wavelet coefficients generated by a 2D discrete wavelet transform (DWT) of spatial maps of fMRI time series statistics. We also describe and apply change-point detection with recursive hypothesis testing methods that can be used to define a threshold unique to each level and orientation of the 2D-DWT, and Bayesian methods, incorporating a formal model for the anticipated sparseness of wavelet coefficients representing the signal or true image. The sensitivity and type I error control of these algorithms are comparatively evaluated by analysis of "null" images (acquired with the subject at rest) and an experimental data set acquired from five normal volunteers during an event-related finger movement task. We show that all three wavelet-based algorithms have good type I error control (the FDR method being most conservative) and generate plausible brain activation maps (the Bayesian method being most powerful). We also generalise the formal connection between wavelet-based methods for simultaneous multiresolution denoising/hypothesis testing and methods based on monoresolution Gaussian smoothing followed by statistical testing of brain activation maps.

Algorithms↗

Cortical local circuit axons do not mature after early deafferentation.

The processes underlying development, refinement, and retention of the intracortical connections critical for the function of the mammalian brain are unknown. Horseradish peroxidase-labeled fibers in mouse somatosensory barrel cortex, which is patterned like the whiskers on the contralateral face from which it receives inputs, were evaluated by automated image analysis. The sensory nerve to the whiskers was sectioned on postnatal day 7, after the whisker map is set. The deprived barrel cortices, examined in adults, showed drastically diminished intracortical projections relative to normal controls, although the map of the whiskers in the cortex was unchanged. This demonstrates anatomically that the normal pattern of intracortical connections, like the normal sensory map, is dependent upon the sensory periphery four synapses away.

Afferent Pathways↗

Spontaneous neural activity is required for the establishment and maintenance of the olfactory sensory map.

We have developed a genetic approach to examine the role of spontaneous activity and synaptic release in the establishment and maintenance of an olfactory sensory map. Conditional expression of tetanus toxin light chain, a molecule that inhibits synaptic release, does not perturb targeting during development, but neurons that express this molecule in a competitive environment fail to maintain appropriate synaptic connections and disappear. Overexpression of the inward rectifying potassium channel, Kir2.1, diminishes the excitability of sensory neurons and more severely disrupts the formation of an olfactory map. These studies suggest that spontaneous neural activity is required for the establishment and maintenance of the precise connectivity inherent in an olfactory sensory map.

Action Potentials↗

The left ventricular end-systolic pressure and pressure-volume index. Comparison between invasive and auscultatory arm pressure measurements.

The slope of the left ventricular (LV) end-systolic pressure-volume relation (ESPVR) has been established as a valuable clinical method to assess LV contractile function independent of LV loading factors. The purpose of the present study was to evaluate whether the ESPVR could be reliably determined from auscultatory blood pressure (BP) measurements and from LV volume measurement by contrast ventriculography (CVG). Twenty-four patients with suspected or known ischemic heart disease were studied by cardiac catheterization with simultaneous, blinded, intravascular and auscultatory pressure measurements. LV volume was determined by CVG. The auscultatory mean arterial blood pressure (MAP) derived from: [formula: see text] was found to be a useful measure of the LV end-systolic pressure in this connection. The correlation between invasively measured LV end-systolic pressure (ESP) and MAP was highly significant (r = 0.82; SEE = 6.9 mmHg; p = 0.001). The correlation between invasively and semi-invasively measured ESPVR fell close to the line of identity (r = 0.99; SEE = 0.23 mmHg.mL-1; p < 0.001). The replacement of ESP by MAP induced only a minimal error in the assessment of the ESPVR. A complete noninvasive determination of the ESPVR and LV contractility therefore seems possible by using the MAP and by measuring the end-systolic volume by radionuclide ventriculography or by echocardiography.

Adult↗

Information retrieval maps for biomedical research.

Integration of computer-based information sources should be useful for biomedical research. An information retrieval map is a graphical representation of a set of expert rules for integrating computer-based information sources based on the data connections among those information sources. The use and implementation of an information retrieval map for sequence alignment is described.

Computer Communication Networks↗

Area and layer patterning in the developing cerebral cortex.

Two anatomical patterns characterize the neocortex, and both are essential for normal cortical function. First, neocortex is divided into anatomically distinct and functionally specialized areas that form a species-specific map. Second, neocortex is composed of layers that organize cortical connectivity. Recent studies of layer and area development have used time-lapse microscopy to follow cortical cell division and migration, gene arrays to find layer- or area- specific regulatory genes, time- and region- specific manipulations of candidate genes, and optical imaging to compare area maps in wild type with genetically altered mice. New observations clarify the molecular and cellular mechanisms that generate each pattern, and stress the links between layer and area formation.

Animals↗

An ecological map of Europe: why and how?

After a recall of the recent emergence of the great ecological problems on the scale of the European continent and of the privileged use of vegetation maps as an ecological tool, a cartographic synthesis of the main plant formations in Europe is submitted on the basis of a hierarchized and numerized nomenclature of the vegetation units. Examples of connections between vegetation and ecology, as suggested or facilitated by this map, are given: use of the monthly ombrothermic diagrams as a privileged tool, thermic limits of the boreal zone, indicative value of the Mediterranean xerothermic area, predictive models of the geographical shifts of the great ecosystems according to the expected climate changes.

Ecology↗

Correlation between patterns of horizontal connectivity and the extend of short-term representational plasticity in rat motor cortex.

Plasticity of representational maps in adult cerebral cortex has been documented in both sensory and motor cortex, but the anatomical basis for cortical plasticity remains poorly understood. To investigate horizontal connectivity in primary motor cortex (M1) as a putative anatomical substrate for short-term, functional plasticity of adult motor cortical representations, a combination of electrical stimulation and biocytin labeling was used to examine pre-existing patterns of intrinsic connections in adult rat M1 in relationship to the pattern of reorganization of the motor movement may induced by transection of the contralateral facial nerve. Two hours after nerve cut, small, circumscribed regions of the forelimb representation expanded medially into territory previously devoted to the vibrissae representation. Outside of this novel, expanded forelimb region, no forelimb movement could be evoked from the former vibrissae representation at any time over the period of hours tested, thus representing silent cortex. Injections placed into vibrissae cortex representing the newly expanded forelimb representation gave rise to labeled axons and dense terminal fiber labeling which crossed the forelimb/vibrissae border and extended up to 1.2 mm within the low-threshold forelimb representation. In contrast, injections placed into silent vibrissae cortex gave rise to labeled axons and terminal boutons which remained mostly restricted to the original vibrissae representation, with only sparse projections that crossed into the low-threshold forelimb representation. Thus, these results suggest that the extent of short-term, functional reorganization of M1 induced within the first several hours following peripheral nerve cut is mediated, and constrained, by an anatomical framework of pre-existing, horizontal projections which traverse representation borders.

Animals↗

Cortical and thalamic connections of the parietal ventral somatosensory area in marmoset monkeys (Callithrix jacchus).

Microelectrode mapping methods were used to define the parietal ventral somatosensory area (PV) on the upper bank of the lateral sulcus in five marmosets (Callithrix jacchus). In the same animals, neuroanatomical tracers were placed into electrophysiologically identified sites in PV and/or the second somatosensory area (S2). Foci of anterograde and retrograde label were related to electrophysiological maps of cortical areas and cortical and thalamic architecture. The results lead to the following conclusions: (1) Multiunit recordings from cortex on the upper bank of the lateral sulcus demonstrate that PV is somatotopically organized, with the face representation adjoining area 3b and the hindlimb and tail representations away from this border in cortex deep on the upper bank of the lateral sulcus. The forelimb representation is caudal in PV adjacent to the S2 forelimb representation. The body surface representation in PV approximates a mirror image of that in S2; (2) Areas PV and S2 are less myelinated and have less cytochrome oxidase enzyme activity than area 3b; (3) The ventroposterior inferior nucleus (VPI) of the thalamus provides the major somatosensory projections to PV. PV is reciprocally connected with VPI and anterior pulvinar; (4) PV has ipsilateral cortical connections with areas 3a, 3b, 1, and M1 and higher order somatosensory fields, and at least most of these connections are somatotopically matched; and (5) Callosal connections of PV are with S2 and PV of the other cerebral hemisphere. These results further establish PV as one of at least four somatosensory areas of the lateral sulcus of primates.

Animals↗

Putting smell on the map.

The vertebrate olfactory system must cope with a staggering developmental problem: how to connect millions of olfactory neurons expressing different odorant receptors to appropriate targets in the brain. Recent studies demonstrate remarkable plasticity in integrating novel olfactory neurons into this circuitry.

Animals↗

X-ray scattering used to map the preferred collagen orientation in the human cornea and limbus.

Many properties of connective tissues are governed by the organization of the constituent collagen. For example, the organization of collagen in the cornea and the limbus, where the cornea and sclera meet, is an important determinant of corneal curvature and hence of the eye's focusing power. We have used synchrotron X-ray scattering to map the orientation of the collagen fibrils throughout the human cornea, limbus, and adjacent sclera. We demonstrate a preferred orientation of collagen in the vertical and horizontal directions that is maintained to within about 1 mm from the limbus, where a circular or tangential disposition of fibrils occurs. The data are also used to map the relative distribution of both the total and the preferentially aligned collagen in different parts of the tissue, revealing considerable anisotropy. The detailed structural information provided is an important step toward understanding the shape and the mechanical properties of the tissue.

Animals↗

Endothelin-1 induces expression of matrix-associated genes in lung fibroblasts through MEK/ERK.

The endothelins are a family of endothelium-derived peptides that possess a variety of biological activities, including potent vasoconstriction. Endothelin-1 (ET-1) is up-regulated during tissue repair and pulmonary fibrosis. Here, we use genome-wide expression array analysis to show that the addition of ET-1 (100 nm, 4 h) to normal lung fibroblasts directly induces expression of matrix and matrix-associated genes, including the profibrotic protein CCN2 (connective tissue growth factor, or CTGF). ET-1 induces the MEK/ERK MAP kinase pathway in fibroblasts. Blockade of the MEK/ERK kinase pathway with U0126 abrogates the ability of ET-1 to induce expression of matrix and matrix-associated mRNAs and the CCN2 protein. The CCN2 promoter possesses an ET-1 response element, which maps to the previously identified basal control element-1 (BCE-1) site. Our results suggest that ET-1 induces a program of matrix synthesis in lung fibroblasts and that ET-1 may play a key role in connective tissue deposition during wound repair and in pulmonary fibrosis.

Endothelin-1↗