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Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex.

'What' and 'where' visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory-prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively.

Acoustic Stimulation↗

Phosphorylation of transcription factors and control of the cell cycle.

Protein phosphorylation has evolved as the most versatile posttranslational modification widely used by cells. Signal transduction pathways mediated by activation of MAP kinases and protein kinase C trigger the exit of cells from the quiscence (Go-->G1 transition). Indeed, binding of growth factors at the cell surface triggers their receptors, usually possessing a tyrosine kinase on the cytoplasmic side, to phosphorylate other molecules passing on the information sequentially to GRB2 protein, to p21ras, to c-Raf-1, to MAP kinase kinase, to MAP kinase, to p90rsk, to transcription factors. Activated PKC, MAP kinase, and pp90src can translocate to the nucleus where they phosphorylate a number of protein transcription regulators in a cell cycle-dependent manner or in response to cell stimulation for exit from quiescence. The cell cycle is mainly regulated by p34cdc2 or otherwise called cdc2 in association with cyclins B at G2/M and by Cdk2 in association with cyclins A, D1, and E at G1/S checkpoints; phosphorylation of histone H1 and lamins by cdc2 triggers chromosome assembly and nuclear envelope breakdown, respectively, as a prelude to mitosis. Cdc2 activities functioning as a G2/M regulator are controlled by its phosphorylation and dephosphorylation at Ser/Thr residues. MAP kinases might be the missing link in the chain connecting the Go to G1 transition with the cell cycle regulation, whereas phosphorylation of replication protein factors, retinoblastoma, and p53 might link the G1 to S transition with the control of DNA synthesis. A number of transcription factors are known to stimulate DNA replication, including p53, c-Myc, AP-1, Oct-1, T-antigen; the DNA binding activities of all these proteins and their interaction with other transcription factors are controlled by phosphorylation. The nuclear import of several proteins including NF kappa B, Dorsal, glucocorticoid receptor, ISGF3, rNFIL-6, T antigen, and the kinases PKC, MAP, and p90rsk, are dependent on their phosphorylation at specific sites. Histone phosphorylation stimulated at discrete stages of the cell cycle or in response to cAMP or other stimuli might induce profound changes in chromatin organization.

Amino Acid Sequence↗

Anatomical correlates of representational map reorganization induced by partial vibrissectomy in the barrel cortex of adult mice.

We examined the potential for changes in cortical connectivity to accompany long-term plastic changes in functional cortical representations of mystacial vibrissae. Plasticity in the barrel cortex of young adult mice was evoked by vibrissectomy that spared row C of whiskers. We found that 2-deoxyglucose brain mapping causes a progressive expansion of cortical representation of the spared vibrissae. Two months after vibrissectomy, when the width of the cortical map of the spared row of vibrissae doubled, living cortical slices of the barrel cortex were injected with fluorescent dextrans. The injections were centered on spared, deprived and control vibrissal columns. The injections labeled three intracortical projection systems: (i) local connections from one vibrissal column to neighboring columns; (ii) long-range projections running in the septa and walls of the barrels and spanning several barrels; and (iii) very-long-range fibers running horizontally in the lower part of layer V. The local, short-range projection system was analysed following small injections into the centers of columns in layers III and IV. We found that injections into spared barrels labeled axons extending for significantly greater distances in all layers (except layer V), and labeled cell bodies situated significantly further, than after injections into deprived or control barrels. Also, the total axonal density labeled by injections into the spared barrel was higher by 70% than for the deprived or control barrels. Alterations of topographical maps in adult somatosensory cortex may occur immediately after functional denervation, but may also increase with time, as in the case of our experimental situation. Our results indicate that persistent, long-term plastic change can remodel connectivity in the barrel cortex.

Animals↗

Frontal and parieto-temporal cortical ablations and diaschisis-like effects on auditory neurocognitive potentials evocable from apparently intact ipsilateral association areas in humans: five case reports.

The aim of this study was to investigate the effects of disruption on the warning auditory S1-elicited ERP and CNV complexes recordable on the site and on remote ipsilateral apparently normal anatomo-functionally interconnected brain regions. These effects in some cases showed aspects of a probable diaschisis-like phenomenon, due to resections of extensive frontal association cortex or of primary and secondary sensory parieto-temporal areas damaged by differing pathological processes. Using a standard CNV paradigm, 21/19 EEG electrodes connected with three different references, and scalp-topographic bidimensional mapping analysis, the S1 auditory binaural/monaural clicks N1a,b,c, P2, N2, P3 and CNV waves were recorded in 10 normal subjects and 11 patients. Nine of the latter had been submitted to unilateral frontal dorsolateral cortex ablation, one to bihemispheric dorsomedial cortex ablation, and one to unilateral ablation of sensory parieto-temporal cortex and underlying white matter, verified through CT/MRI examinations. No true S1ERP/CNV components were recordable over the ablated cortical areas, whereas normal ERP/CNV complexes were observable on the intact hemispheres. In five patients, four of whom with frontocortical ablations, the S1 ERP/CNV complexes appeared severely diminished or disrupted, in two cases in a slow, partially-reversible manner, also in the neuroradiologically normal ipsilateral functionally-connected post-rolandic sensory and association areas. Similar deactivation of some ERP components was observed in reverse on the unilateral dorsolateral frontocortical region in the fifth patient with parieto-temporal cortex ablation. Even when they are partially reversible, these ipsilateral remote ERP changes in apparently intact brain regions, due to ablations of functionally-interconnected cortical formations, probably reflect cortical deactivation or simply dysfacilitation deriving from functional unilateral diaschisis. If these changes are instead irreversible they may probably be interpreted as transneuronal degeneration phenomena, though they are not at present easy to document either neuroradiologically or electroclinically.

Adult↗

A high-density integrated genetic linkage and radiation hybrid map of the laboratory rat.

The laboratory rat (Rattus norvegicus) is a key animal model for biomedical research. However, the genetic infrastructure required for connecting phenotype and genotype in the rat is currently incomplete. Here, we report the construction and integration of two genomic maps: a dense genetic linkage map of the rat and the first radiation hybrid (RH) map of the rat. The genetic map was constructed in two F2 intercrosses (SHRSP x BN and FHH x ACI), containing a total of 4736 simple sequence length polymorphism (SSLP) markers. Allele sizes for 4328 of the genetic markers were characterized in 48 of the most commonly used inbred strains. The RH map is a lod >/= 3 framework map, including 983 SSLPs, thereby allowing integration with markers on various genetic maps and with markers mapped on the RH panel. Together, the maps provide an integrated reference to >3000 genes and ESTs and >8500 genetic markers (5211 of our SSLPs and >3500 SSLPs developed by other groups). [Bihoreau et al. (1997); James and Tanigami, RHdb (http:www.ebi.ac.uk/RHdb/index.html); Wilder (http://www.nih.gov/niams/scientific/ratgbase); Serikawa et al. (1992); RATMAP server (http://ratmap.gen.gu.se)] RH maps (v. 2.0) have been posted on our web sites at http://goliath.ifrc.mcw.edu/LGR/index.html or http://curatools.curagen.com/ratmap. Both web sites provide an RH mapping server where investigators can localize their own RH vectors relative to this map. The raw data have been deposited in the RHdb database. Taken together, these maps provide the basic tools for rat genomics. The RH map provides the means to rapidly localize genetic markers, genes, and ESTs within the rat genome. These maps provide the basic tools for rat genomics. They will facilitate studies of multifactorial disease and functional genomics, allow construction of physical maps, and provide a scaffold for both directed and large-scale sequencing efforts and comparative genomics in this important experimental organism.

Alleles↗

Impaired effective cortical connectivity in vegetative state: preliminary investigation using PET.

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [18F]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients.

Adult↗

Analysis of the topographical organization of olfactory epithelium projections in the rat.

The degree of topographical organization of epithelium-to-bulb connections in 15-day-old rats was analyzed from the complete mapping of these projections previously described by using the HRP retrograde tracing method. We performed HRP placements in the antero-posterior (anterior, central and posterior injections) and dorso-ventral bulbar axes. Results demonstrated: lack of transposition of any plane of the epithelial sheet along the antero-posterior axis in the bulb which indicated a typical diffuse distribution of projections along this bulbar plane; a general tendency of the medial, lateral, dorsal and ventral epithelial regions to project to homologous bulbar surfaces; however, this transposition was always relative; the importance of the dorso-ventral bulbar axis in the somatotopic organization of projections since this plane was a common plane on which the different mucosal axes were represented. These results suggest that the topographical organization of projections reflects the ontogenetically determined epithelium-to-bulb connections.

Afferent Pathways↗

Ephrin-As and patterned retinal activity act together in the development of topographic maps in the primary visual system.

The development of topographic maps in the primary visual system is thought to rely on a combination of EphA/ephrin-A interactions and patterned neural activity. Here, we characterize the retinogeniculate and retinocollicular maps of mice mutant for ephrins-A2, -A3, and -A5 (the three ephrin-As expressed in the mouse visual system), mice mutant for the beta2 subunit of the nicotinic acetylcholine receptor (that lack early patterned retinal activity), and mice mutant for both ephrin-As and beta2. We also provide the first comprehensive anatomical description of the topographic connections between the retina and the dorsal lateral geniculate nucleus. We find that, although ephrin-A2/A3/A5 triple knock-out mice have severe mapping defects in both projections, they do not completely lack topography. Mice lacking beta2-dependent retinal activity have nearly normal topography but fail to refine axonal arbors. Mice mutant for both ephrin-As and beta2 have synergistic mapping defects that result in a near absence of map in the retinocollicular projection; however, the retinogeniculate projection is not as severely disrupted as the retinocollicular projection is in these mutants. These results show that ephrin-As and patterned retinal activity act together to establish topographic maps, and demonstrate that midbrain and forebrain connections have a differential requirement for ephrin-As and patterned retinal activity in topographic map development.

Animals↗

Forest Canopy Stratification-Is It Useful?

It has long been recognized that the forest canopy has a complex structure that is significant for environmental interactions, regeneration, growth, and biotic habitat. Not only is the structure variously complex, but also there are many ways to conceptualize that complexity. Yet the persistent theme when considering the structure of canopies continues to be that of stratification: whether structural units are arranged in layers above the ground. We examined the use of the terms "stratification," "layering," and others in connection with canopy structure and found they had various meanings (often only implied) that were difficult to reconcile and to measure. We applied the definitions to the structure of a single, well-studied canopy located in Virginia, U.S.A., and found they failed to define consistently and clearly the presence, number, or location of strata. Additionally, we found the concept had limitations related to scale dependence, point of reference, and spatial averaging. Thus, asserting that a forest is stratified or naming the number of layers generally provided no guide to its structure. We propose alternative ways of conceptualizing and studying the forest canopy that avoid most of the problems associated with stratification. Among these are direct measurement and mapping of structural and environmental variables that have clear potential connections with canopy functions and viewing the distribution of structures or environmental conditions within the canopy as ecological gradients.

canopy↗

Retinotopic refinement of the regenerating goldfish optic tract is not linked to activity-dependent refinement of the retinotectal map.

The cut optic nerve of a goldfish can regenerate, restoring an orderly projection from the retina to the optic tectum. At first, regenerating axons make transient connections, many of them in inappropriate tectal locations. Later, their arrangement is gradually refined into an accurate retinotectal map by a process that depends on afferent activity. On their way to the tectum, many regenerating axons make erroneous choices between the two arms (brachia) of the optic tract. However, since they commonly possess divergent collateral branches, a secondary refinement of the brachial pattern can occur by selective collateral elimination. How or why a particular collateral is lost is not known, but we have previously suggested that sibling branches might compete to form stable tectal synapses, implying that there might be a causal link between refinement of the brachial pattern and refinement of the retinotectal map. In this paper, we have tested directly for such a link, blocking map refinement with tetrodotoxin (TTX) or stroboscopic light, verifying the effectiveness of the block and measuring the extent of brachial refinement by standard methods in experimental and control fish. Both TTX and stroboscopic light reliably prevented map refinement, their results being indistinguishable. However, neither had even the slightest detrimental effect on brachial refinement, either 42 days or 70 days after nerve cut. Evidently, neither activity nor a sharp retinotectal projection is necessary for brachial refinement. Theory and experiment both dictate that the basic projection pattern be controlled by a mechanism (such as chemoaffinity) that is independent of activity, and it would seem that selective collateral loss must depend on the same mechanism.

Animals↗

Discrete states of a protein interaction network govern interphase and mitotic microtubule dynamics.

The cytoplasm of eukaryotic cells is thought to adopt discrete "states" corresponding to different steady states of protein networks that govern changes in subcellular organization. For example, in Xenopus eggs, the interphase to mitosis transition is induced solely by activation of cyclin-dependent kinase 1 (CDK1) that phosphorylates many proteins leading to a reorganization of the nucleus and assembly of the mitotic spindle. Among these changes, the large array of stable microtubules that exists in interphase is replaced by short, highly dynamic microtubules in metaphase. Using a new visual immunoprecipitation assay that quantifies pairwise protein interactions in a non-perturbing manner in Xenopus egg extracts, we reveal the existence of a network of interactions between a series of microtubule-associated proteins (MAPs). In interphase, tubulin interacts with XMAP215, which is itself interacting with XKCM1, which connects to APC, EB1, and CLIP170. In mitosis, tubulin interacts with XMAP215, which is connected to EB1. We show that in interphase, microtubules are stable because the catastrophe-promoting activity of XKCM1 is inhibited by its interactions with the other MAPs. In mitosis, microtubules are short and dynamic because XKCM1 is free and has a strong destabilizing activity. In this case, the interaction of XMAP215 with EB1 is required to counteract the strong activity of XKCM1. This provides the beginning of a biochemical description of the notion of "cytoplasmic states" regarding the microtubule system.

Animals↗

Recent advances in plant MAP kinase signalling.

Mitogen activated protein kinases (MAPK) are important mediators in signal transmission, connecting the perception of external stimuli to cellular responses. MAPK cascades are involved in signalling various biotic and abiotic stresses, like wounding and pathogen infection, temperature stress or drought, but are also involved in mediating the action of some plant hormones, such as ethylene and auxin. Moreover, MAPKs have been implicated in cell cycle and developmental processes. In Arabidopsis mutant screens and in vivo assays several components of plant MAPK cascades have been identified. This review gives an update of recent advances in plant MAPK signalling and discusses the emerging mechanisms of some selected MAPK pathways.

Cell Cycle↗

[Is insertion/deletion polymorphism angiotensin-converting enzyme gene responsible for long-life?].

I/D polymorphism of ACE gene is the most frequent examined polymorphism and probably very strongly connected to pathology. The majority of studies describe negative influence of allele D on frequency and course of given diseases. The result of negative effect of this allele should be visible in people with long life expectancy. To answer the question: is I/D polymorphism ACE gene responsible for long-life, a comparison was made of the genotype map of a group of 101 long-life subjects with a group of 494 younger persons. The examination used polymerase chain reaction methods. The results were calculated using the programme Statistica 5.1 PL. One used the independent chi 2 test and Odds Ratio to compare the genotype map and localisation of alleles. After having made comparative examination no connection was made between I/D polymorphism ACE gene and long-life.

Aged↗

Mapping and monitoring contaminated-sediment geometry and stability.

Environment Canada's National Water Research Institute (NWRI) conducts research on freshwater contaminated sediments, much of which is focused on designated areas of concern in the Great Lakes and their connecting channels. This paper reviews new acoustic and video equipment and procedures developed to map the geometry and stability of the sediments, and describes their applications. A RoxAnn acoustic seabed-classification system is used for mapping bottom-sediment types and locating the deposits of fine-grained sediments with which contaminants are associated. The system uses the acoustic properties of sediments to distinguish textural types ranging from mud to boulders, and displays the data as they are collected. The sediment thickness is measured with a weighted video-acoustic tripod which is lowered into the sediments to refusal, and which recorded penetration with a video camera or an echosounder transducer. The stability of the contaminated sediments was monitored with a bottom-mounted, high-precision echo sounder-digitizer, which logs changes in the position of the sediment-water interface produced by erosion or deposition. The same procedure can be used in capping or dredging projects to track bottom changes as they occur, or they can be measured by pre- and post-project mapping of bathymetry and morphology with sweep-sonar or side-scan sonar equipment. The new equipment and procedures have been successfully applied to a number of areas of concern in the Great Lakes basin. They provide a faster and more detailed characterization of sediment properties and geometry than was previously available, and have been particularly effective in optimizing sampling surveys and monitoring remediation projects.

Animals↗

A neural network model as a globally coupled map and applications based on chaos.

First, a neural network model as the globally coupled map (GCM) is proposed. The model is obtained by modification of a Hopfield network model that has a negative self-feedback connection. Second, information processed by this model is interpreted in terms of the variety of the maps acting on the network elements, and a new, dynamic information processing model is described. The search for information using vague keywords, and solution of the traveling salesman problem (TSP) are introduced as applications.

Journal Article↗

Interhemispheric connections between primary visual areas: beyond the midline rule.

In the last five years, a number of detailed anatomical, electrophysiological, optical imaging and simulation studies performed in a variety of non-human species have revealed that the functional organization of callosal connections between primary visual areas is more elaborate than previously thought. Callosal cell bodies and terminals are clustered in columns whose correspondence to features mapped in the visual cortex, such as orientation and ocularity, are starting to be understood. Callosal connections are not restricted to the vertical midline representation nor do they establish merely point-to-point retinotopic correspondences across the hemispheres, as traditionally believed. In addition, anatomical studies have revealed the existence of an ipsilateral component of callosal axons. The aim of this short review is to propose how these new data can be integrated into an updated scheme of the circuits responsible for assembling the primary visual field map.

Animals↗

TGF-beta1 increases proliferation of airway smooth muscle cells by phosphorylation of map kinases.

BACKGROUND: Airway remodeling in asthma is the result of increased expression of connective tissue proteins, airway smooth muscle cell (ASMC) hyperplasia and hypertrophy. TGF-beta1 has been found to increase ASMC proliferation. The activation of mitogen-activated protein kinases (MAPKs), p38, ERK, and JNK, is critical to the signal transduction associated with cell proliferation. In the present study, we determined the role of phosphorylated MAPKs in TGF-beta1 induced ASMC proliferation. METHODS: Confluent and growth-arrested bovine ASMCs were treated with TGF-beta1. Proliferation was measured by [3H]-thymidine incorporation and cell counting. Expressions of phosphorylated p38, ERK1/2, and JNK were determined by Western analysis. RESULTS: In a concentration-dependent manner, TGF-beta1 increased [3H]-thymidine incorporation and cell number of ASMCs. TGF-beta1 also enhanced serum-induced ASMC proliferation. Although ASMCs cultured with TGF-beta1 had a significant increase in phosphorylated p38, ERK1/2, and JNK, the maximal phosphorylation of each MAPK had a varied onset after incubation with TGF-beta1. TGF-beta1 induced DNA synthesis was inhibited by SB 203580 or PD 98059, selective inhibitors of p38 and MAP kinase kinase (MEK), respectively. Antibodies against EGF, FGF-2, IGF-I, and PDGF did not inhibit the TGF-beta1 induced DNA synthesis. CONCLUSION: Our data indicate that ASMCs proliferate in response to TGF-beta1, which is mediated by phosphorylation of p38 and ERK1/2. These findings suggest that TGF-beta1 which is expressed in airways of asthmatics may contribute to irreversible airway remodeling by enhancing ASMC proliferation.

Animals↗

Plasticity of cutaneous primary afferent projections to the spinal dorsal horn.

Reorganization of the somatotopic map in the spinal dorsal horn may be elicited by a variety of deafferenting lesions, including transection of peripheral nerves or dorsal roots, or the application of neurotoxins. While such lesions give rise to a variety of neurochemical and morphological changes in the dorsal horn, collateral sprouting of intact primary afferents appears to be minimal. Recently, intraaxonal injection of neurobiotin has allowed visualization of the entire spinal arborization of single A beta primary afferent fibers in animals where the somatotopy of the relevant region of dorsal horn has also been mapped. In contrast to the somatotopic precision of the terminal fields of peripheral nerves suggested by transganglionic tracing, these studies have shown that afferents make connections many millimeters rostral and caudal to the region where their receptive field is represented in the somatotopic map. Intracellular recording from dorsal horn neurons has further shown that these long-ranging projections make functional, but weak, synaptic connections. Thus the functional somatotopic reorganization that follows nerve lesions in mature animals might be explained simply by an increased synaptic efficacy of these existing projections. In contrast to the negligible sprouting of intact A beta primary afferents, those undergoing axonal regeneration exhibit dense collateral sprouting into deafferented regions of the dorsal horn, particularly the superficial laminae, where the terminal arbors of many small (A delta and C) nociceptive afferent fibres degenerate following peripheral nerve lesions. The inappropriate connections made by these collateral sprouts may partly underlie the painful sequelae of nerve injury in man.

Animals↗