Showing papers in "Proceedings of The Royal Society B: Biological Sciences in 1981"

Directional Selectivity and its Use in Early Visual Processing

Abstract: The construction of directionally selective units, and their use in the processing of visual motion, are considered. The zero crossings of $ abla ^{2}$G(x, y) * I(x,y) are located, as in Marr & Hildreth (1980). That is, the image is filtered through centre-surround receptive fields, and the zero values in the output are found. In addition, the time derivative $\delta $[$ abla ^{2}$G(x, y) * I(x, y)]/$\partial $t is measured at the zero crossings, and serves to constrain the local direction of motion to within 180 degrees. The direction of motion can be determined in a second stage, for example by combining the local constraints. The second part of the paper suggests a specific model of the information processing by the X and Y cells of the retina and lateral geniculate nucleus, and certain classes of cortical simple cells. A number of psychophysical and neurophysiological predictions are derived from the theory.

On the stochastic properties of single ion channels.

Abstract: It is desirable to be able to predict, from a specified mechanism, the appearance of currents that flow through single ion channels (a) to enable interpretation of experiments in which single channel currents are observed, and (b) to allow physical meaning to be attached to the results observed in kinetic (noise and relaxation) experiments in which the aggregate of many single channel currents is observed. With this object, distributions (and their means) are derived for the length of the sojourn in any specified subset of states (e.g. all shut states). In general these are found to depend not only on the state in which the sojourn starts, but also on the state that immediately follows the sojourn. The methods described allow derivation of the distribution of, for example, (a) the number of openings, and total length of the burst of openings, that may occur during a single occupancy, and (b) the apparent gap between such bursts. The methods are illustrated by their application to two simple theories of agonist action. The Castillo--Katz (non-cooperative) mechanism predicts, for example, that the number of openings per occupancy, and the apparent burst length, are independent of agonist concentration whereas a simple cooperative mechanism predicts that both will increase with agonist concentration.

Morphology and Mosaic of on- and off-Beta Cells in the Cat Retina and Some Functional Considerations

Abstract: The beta type of ganglion cell can be subdivided in Golgi-stained whole mounts of the cat retina according to the branching level of the dendritic tree in the inner plexiform layer. The dendritic branching level of on-beta cells is nearer to the cell body; that of off-beta cells is about 10 $\mu $m further outwards. After horseradish peroxidase (HRP) injection into the lateral geniculate nucleus all beta cells were labelled. In this way it is shown that about 55% of all ganglion cells, irrespective of retinal topography, are beta cells. The spatial distribution of on- and off-beta cells was studied from the HRP-labelled material. On-beta cells form a lattice with regular inter-cell spacings; off-beta cells are also regularly arrayed. The two lattices are superimposed independently of each other. Beta cells are commonly assumed to be associated with the resolution of fine detail in the cat visual system. The mosaic of beta cells imposes some constraints and permits some predictions to be made with respect to the cat's visual discrimination.

Morphology and Topography of on- and off-Alpha Cells in the Cat Retina

Abstract: Neurofibrillar staining methods were found to stain all alpha cells of the cat retina completely, that is the perikaryon, the axon and the dendritic branches. The dendrites of the alpha cells in vertical sections were found to be unistratified and to occupy two narrow strata in the outer half of the inner plexiform layer. This difference in branching level could also be observed in whole-mount preparations and it has been demonstrated in the preceding paper (Peichl & Wassle 1981) that it corresponds to the physiological on-off dichotomy. Thus the topographical distribution of on- and off-alpha cells could be studied. They are found to occur in about equal numbers. Both on- and off-alpha cell perikarya form a regular lattice and both lattices are superimposed independently. The dendritic branches of neighbouring alpha cells overlap and each retinal point is covered by the dendritic field of at least one on- and one off-alpha cell. The dendritic trees of on-alpha cells seem to have more small branches and are on the average smaller than those of off-alpha cells. The density of alpha cells was found to peak in the central area whence it continuously decreased towards the retinal periphery.

Olfactory Mechanisms in the Moth Manduca sexta: Response Characteristics and Morphology of Central Neurons in the Antennal Lobes

Abstract: The antennal lobes of the moth Manduca sexta are composed of two distinct classes of central neurons: local interneurons, involved in sensory processing within the lobe, and output neurons, the relay elements carrying sensory information to higher neuropil centres in the brain. The different types of neurons in each class share many characteristics. All of the local interneurons have extensive multiglomerular dendritic arborizations and lack distinct axons while all of the output neurons have uniglomerular dendritic arborizations. In addition to these general characteristics the central neurons of the antennal lobes also possess a distinct sexual dimorphism. Only the male moth responds to the female sex pheromone. All of the central neurons in the antennal lobe of the male moth that respond to pheromone have dendritic branches located in the macroglomerular complex, a male-specific neuropil region. Two types of pheromone-sensitive local interneurons have been described morphologically and physiologically while a single type of output neuron has been found that has a dendritic arborization in the macroglomerular complex.

The Ferrier Lecture, 1980: Critical Limiting Factors in the Design of the Eye and Visual Cortex

Abstract: The main factors limiting the performance of the peripheral parts of the visual system can be specified, and doing this clarifies the nature of the interpretive tasks that must be performed by the central parts of the system. It is argued that the critical factor that hinders development of better resolving power is the difficulty of confining light within the waveguide-like outer segment, and that for sensitivity this critical factor is the thermal decomposition of photosensitive pigments. Knowledge of these limits makes many surprising details of the eye intelligible. Understanding the difficulties posed by the narrow dynamic range of nerve fibres may give similar insight into the coding of the retinal image for transmission to the brain. Our level of understanding changes when we come to the visual cortex, for although we do not lack good anatomical and neurophysiological data, these do not make the principles of operation self-evident in the way that the structure of the eye immediately suggests that it is an image-forming device. The cortex converts the representation of the visual field that it receives into reliable knowledge of the world around us, and the trouble may be that we lack good models of how this can be done. A system that can respond to single quanta and resolve almost to the diffraction limit is unlikely to employ grossly inefficient methods for those higher functions upon which its whole utility depends, and so it is worth seeking out the limiting factors. The quality of human performance at certain higher perceptual tasks is high compared with the limit of reliable statistical inference; hence much of the sample of information available in a visual image must be effectively utilized. But there are strong limitations on the connectivity in the cortex, so that one is forced to consider how the relevant information can be collected together. Three stages of dealing with the visual image are proposed: the improvement of the cortical map in primary visual cortex by processes analogous to spatial and temporal interpolation; the detection of linking features in this map; and the concentration of this information by non-topographical mapping in adjacent visual areas.

Pathway Selection by Embryonic Chick Motoneurons in an Experimentally Altered Environment

Abstract: To characterize cues used by motoneuron axons to reach their appropriate targets, connectivity patterns within the embryonic chick hindlimb have been analysed after early experimental manipulations of the limb or spinal cord. The manipulations altered the anterior-posterior (a.-p.) relationship between motoneurons within the lumbosacral motor column and their specific targets in the limb. Primary emphasis was placed on analysing the pathways taken by embryonic motoneuron axons at stages 23-36 which had been orthogradely labelled by horseradish peroxidase (HRP) injection into the motor column. Motoneuron pool topography and functional patterns of connectivity were also identified by retrograde HRP labelling and spinal cord stimulation coupled with electromyographic recording. With small shifts in position, as in two or three segment a.-p. cord reversals or a.-p. limb shifts, motoneuron axons frequently entered the appropriate plexus but in an inappropriate spinal nerve sequence. Despite this, axons altered their course to innervate specifically and consistently their correct target. When motoneuron axons entered an inappropriate plexus as the result of a greater positional shift (i.e. more extensive cord reversal or limb shift) or in experiments where posterior cord segments were replaced with anterior cord segments and supernumerary limbs were added, they behaved in one of two ways. They either formed inappropriate and largely unpatterned or unordered connections or they took totally aberrant paths within the limb to reach their appropriate target. We conclude that axons are capable of responding in a precise and specific manner to environmental cues when displaced up to a certain distance from their target or normal point of entry into the limb. Their failure to form patterned connections at more extreme distances suggests that the cues to which they are responding may be local, or that an axon's ability to respond to them is restricted to subclasses of the motoneuron population.

Pathway selection by chick lumbosacral motoneurons during normal development

Abstract: Pathways taken by motoneuron axons from the lumbosacral lateral motor column to individual hindlimb muscles have been characterized throughout the normal period of outgrowth and the establishment of specific functional connections in the chick embryo. Axon pathways from individual cord segments were identified after injections of horseradish peroxidase (HRP) directly into the cord. Labelled motoneuron axons were then traced through the plexus and major nerve trunks to termination sites within the limb. At stages 23-24 labelled axons within spinal nerves have just reached the base of the limb and have begun to converge and form the crural and the ischiadic plexus. Even at this early stage, before periods of muscle cleavage, motoneuron cell death and muscle nerve formation, axons show no evidence of widespread random distribution within the limb. Rather, they generally maintain their anterior-posterior position as far as the base of the limb. At stages 27-30, although axons to individual muscles were found to course in discrete tracts within the plexus and nerve trunks they also changed their topographical position with respect to other axons. Axon pathways to single muscles were characterized by tracing retrogradely labelled axons back to the cord after injections of HRP into specific muscle nerves. Axons destined for a single muscle are intermingled with other axons in the spinal nerves and proximal plexus but by the distal plexus have converged to form a discrete tract which then diverges as an individual muscle nerve at more distal levels. These observations exclude models for the establishment of specific connections in which there is widespread testing of the environment with removal of projection errors by cell death and/or axon retraction. They also exclude models that require axons to maintain their topographical position with respect to each other throughout their course.

Visual hyperacuity: spatiotemporal interpolation in human vision

Abstract: Stroboscopic presentation of a moving object can be interpolated by our visual system into the perception of continuous motion. The precision of this interpolation process has been explored by measuring the vernier discrimination threshold for targets displayed stroboscopically at a sequence of stations. The vernier targets, moving at constant velocity, were presented either with a spatial offset or with a temporal offset or with both. The main results are: (1) vernier acuity for spatial offset is rather invariant over a wide range of velocities and separations between the stations (see Westheimer & McKee 1975); (2) vernier acuity for temporal offset depends on spatial separation and velocity. At each separation there is an optimal velocity such that the strobe interval is roughly constant at about 30 ms; optimal acuity decreases with increasing separation; (3) blur of the vernier pattern decreases acuity for spatial offsets, but improves acuity for temporal offsets (at high velocities and large separations); (4) a temporal offset exactly compensates the equivalent (at the given velocity) spatial offset only for a small separation and optimal velocity; otherwise the spatial offset dominates. A theoretical analysis of the interpolation problem suggests a computational scheme based on the assumption of constant velocity motion. This assumption reflects a constraint satisfied in normal vision over the short times and small distances normally relevant for the interpolation process. A reasonable implementation of this scheme only requires a set of independent, direction selective spatiotemporal channels, that is receptive fields with the different sizes and temporal properties revealed by psychophysical experiments. It is concluded that sophisticated mechanisms are not required to account for the main properties of vernier acuity with moving targets. It is furthermore suggested that the spatiotemporal channels of human vision may be the interpolation filters themselves. Possible neurophysiological implications are briefly discussed.

Morphological identification of on- and off-centre brisk transient (Y) cells in the cat retina.

Abstract: Brisk transient (Y) cells were recorded extracellularly in the cat retina. The position and shape of their receptive field centres were plotted on a tangent screen, together with retinal landmarks, such as blood vessels adjacent to the recording area. After recording the retina was processed as a whole mount and stained with a reduced-silver method (see appendix). This technique stains the entire alpha cell population including the dendritic trees. Alpha cells are the morphological correlate of the brisk transient cells (Boycott & Wassle 1974; Cleland et al. 1975). Maps of the screen plot and the histological preparation could be accurately superimposed by means of the retinal landmarks and each recorded brisk transient unit could unequivocally be attributed to a particular alpha cell. Alpha cell dendritic trees are unistratified in either of two laminae within the inner plexiform layer: (1) close to the inner nuclear layer border, 'outer alpha cells', or (2) about 10 micrometers further towards the ganglion cell layer, 'inner alpha cells'. This stratification difference can be observed in whole mounts for large populations of cells (Wassle et al. 1981). Of the recorded brisk transient cells, all on-centre units were inner alphas and all off-centre units outer alphas.

Organization and Synaptic Ultrastructure of Glomeruli in the Antennal Lobes of the Moth Manduca sexta: A Study Using Thin Sections and Freeze-Fracture

Abstract: The antennal lobe of the brain of Manduca sexta comprises a central area of coarse neuropil surrounded by dense, spheroidal glomeruli, where all synaptic interactions between antennal-nerve axons and the second-order neurons of the lobe occur. Neuronal interactions in the glomeruli are complex, involving several types of neuritic profiles and mediated by synapses with a one-to-many ratio of pre- to postsynaptic elements. Presynaptic profiles in the glomeruli have been categorized into three types, containing round clear vesicles, large numbers of large dense-cored vesicles, and pleiomorphic clear vesicles, respectively. Preliminary studies of horseradish peroxidase-filled axons and neurons indicate that antennal-nerve axons form synapses without large numbers of dense-cored vesicles and that antennal-lobe neurons not only receive synapses but also may synapse onto other elements in the antennal lobe. A typical synaptic contact involves multiple postsynaptic elements apposed in pairs to an individual presynaptic element. The presynaptic element contains a bar-shaped membrane-associated density, which follows a shallow groove in the membrane and is flanked by synaptic vesicles. Postsynaptic elements are lined by membrane-associated densities in the region opposite to the synaptic bar, and may be observed to participate in serial synapses. Freeze-fracture replicas of the glomerular neuropil contain many membrane specializations that are thought to be presynaptic, some of which resemble those of vertebrate excitatory synapses. At these apparently presynaptic regions, large particles cluster in the P face of the membrane and are often surrounded by plasmalemmal deformations presumably representing sites of exo- or endocytosis. The shape of the predominant type of presynaptic membrane specialization (a plaque) does not match the shape of the presynaptic membrane-associated density (a bar); this raises the possibility that vesicle release occurs at isolated `active zones9 along the presynaptic bar. Postsynaptic sites are represented by clusters of large particles in the E face of the postsynaptic membrane.

The Projection from the Lateral Geniculate Nucleus to the Prestriate Cortex of the Macaque Monkey

Abstract: By injecting the enzyme horseradish peroxidase into the prestriate cortex of the macaque monkey and examining the lateral geniculate nucleus (l.g.n.) for retrograde label, the presence of a direct projection from the l.g.n. to prestriate visual cortex (Brodmann9s areas 18 and 19) was confirmed. Labelled cells occurred in all layers of the l.g.n., distributed in a roughly columnar fashion. The large scatter in cell distribution indicated a lower retinotopic precision for this projection than for the one to area 17. Labelled cells are of a medium to large size and, in each section, a few were located near the laminar border or in interlaminar zones. The functional significance of this projection is discussed.

Autonomic innervation of receptors and muscle fibres in cat skeletal muscle.

Abstract: Cat hindlimb muscles, deprived of their somatic innervation, have been examined with fluorescence and electron microscopy and in teased, silver preparations; normal diaphragm muscles have been examined with electron microscopy only. An autonomic innervation was found to be supplied to both intra- and extrafusal muscle fibres. It is not present in all muscle spindles and is not supplied at all to tendon organs. Fluorescence microscopy revealed a noradrenergic innervation distributed to extrafusal muscle fibres and some spindles. On the basis of the vesicle content of varicosities the extrafusal innervation was identified as noradrenergic (32 axons traced), and the spindle innervation as involving noradrenergic, cholinergic and non-adrenergic axons (14 traced). Some of the noradrenergic axons that innervate spindles and extrafusal muscle fibres are branches of axons that also innervate blood vessels. We cannot say whether there are any noradrenergic axons that are exclusively distributed to intra- or extrafusal muscle fibres. The varicosities themselves may be in neuroeffective association with striated muscle fibres only, or with both striated fibres and the smooth muscle cells in the walls of blood vessels. The functional implications of this direct autonomic innervation of muscle spindles and skeletal muscle fibres are discussed and past work on the subject is evaluated.

Temporal summation of moving images by the human visual system.

Abstract: Measurements of threshold visibility were made as a function of duration of stimulus exposure for small moving dot targets, drifting sinusoidal gratings and moving patches of sinusoidal gratings, to investigate how the human visual nervous system summates over time signals arising from stimuli in motion. At image speeds of less that 16 deg/s, temporal summation is as strong and as extended for moving as for stationary dots (total summation over to about 100 ms). This summation is about twice that which would be expected from separate consideration of the regions of spatial and temporal integration. Measurements with sinusoidal gratings reveal that the nature of the summation depends critically on the spatial frequency of the stimulus: gratings of low spatial frequency summate well when in motion (and only when in motion), whereas those of high spatial frequency summate well only when stationary or in very slow motion. An analogue simulation with electronic filters showed that these psychophysical results are directly predictable from the known transfer characteristics of the human visual system (with the additional assumption of probability summation at threshold). Finally, with small patches of sinusoidal grating, it was established that translation per se across the retina has little effect on temporal summation. This suggests that the results obtained with sinusoidal gratings of large extent are also relevant to small moving stimuli, allowing the summation results obtained with dot stimuli to be discussed in terms of the temporal transfer properties of spatially selective visual detectors. On the basis of these results it is proposed that the extended temporal summation observed for dots in motion results from summation of energy of low spatial frequency present in these stimuli.

Interactions between Insect Immunity and an Insect-Pathogenic Nematode with Symbiotic Bacteria

Abstract: It is well known that some insect-pathogenic nematodes always live in symbiosis with Gram negative bacteria belonging to the genus Xenorhabdus (earlier referred to as Achromobacter). We have here used diapausing pupae of Hyalophora cecropia as a model system and investigated the Mexican strain of Neoaplectana carpocapsae and its bacterium Xenorhabdus nematophilus for their ability to withstand insect immunity separately and in the symbiotic unit. We have prepared a reconstituted nematode containing a streptomycin-resistant mutant of X. nematophilus. In normal pupae LD$\_{50}$ (the injected dose that causes death of 50% of the population) of the bacteria was about 500 cells; for immunized pupae it was 5 $\times $ 10$^{5}$ cells. Cecropia immunity did not affect the nematodes. Fewer than ten nematodes with bacteria were lethal, while LD$\_{50}$ of axenic nematodes was about 500. Immune haemolymph caused lysis of X. nematophilus. Immune proteins P9A and P9B were identified as the active components in Cecropia immunity against X. nematophilus. It was found that the nematodes help the bacteria by excreting an immune inhibitor that selectively destroys both forms of P9 as well as immune protein P5. These results contribute to our understanding of the symbiotic relationship between nematodes and their bacteria and its survival value against induced insect immunity.

On the variety of spatial frequency selectivities shown by neurons in area 17 of the cat.

Abstract: The amplitudes of the responses of over 300 neurons in area 17 of the cat were examined as a function of the spatial frequency of moving sinusoidal gratings. The optimal spatial frequency and the bandwidth of the tuning curves were determined. The bandwidth varied considerably from neuron to neuron. Neurons optimally responsive to high spatial frequencies tended to have narrower tuning curves than those responsive to lower frequencies. Neurons with narrow spatial frequency tuning curves also tended to have narrow orientation tuning curves. These observations suggest that linear spatial summation tends to occur over a relatively constant area of visual field despite marked differences in each neuron's optimal spatial frequency, a prediction of one model of visual analysis. There was little difference in either the optimal spatial frequencies or the bandwidths of tuning for different functional classes of neuron. Neurons with broad tuning curves tended to be restricted to lamina IV and its environs, being concentrated in the deep part of lamina II-III and the upper part of lamina IV ab. Neurons with very low optimal spatial frequencies were uncommon and tended to be found either at the border of laminae II-III and IV or in lamina V. These laminar distributions are discussed with respect to the laminar differences in the projection of l.g.n. X- and Y-cells to the visual cortex.

Collagen Organization in Articular Cartilage, Determined by X-Ray Diffraction, and its Relationship to Tissue Function

Abstract: X-ray diffraction has been used to measure the preferred orientation of the collagen fibrils, and their angular distribution within the tissue, as a function of depth from the articular surface in patellar cartilage. Measurements have been made at four different sites chosen to represent differing surface curvatures and regimes of wear. The orientation of fibrils in the surface layer allows it to oppose the swelling pressure exerted by the gel of hydrated glycosaminoglycans within the cartilage. An intermediate layer (where a bimodal distribution of fibrils is sometimes resolved) allows the orientation of the fibrils to change, with increasing depth, until they are roughly perpendicular to the articular surface. In this deep layer the fibrils can tie into the underlying calcified tissue so as to firmly anchor the cartilage. In the plane of the surface the fibrils tend to be aligned in the direction of stress caused by motion.

Recovery from monocular deprivation in the monkey. III. Reversal of anatomical effects in the visual cortex.

Abstract: Transneuronal autoradiography was used to study the effects of visual deprivation on the ocular dominance stripes in layer IV c of the striate cortex of Erythrocebus patas (Old World) monkeys. The animals were studied after: ( a ) 21–28 days of monocular deprivation starting at, or within, a few days of birth; ( b ) the same treatment followed by a further 3, 6, 15 or 126 days of monocular vision through the originally closed eye (reverse suturing), or followed by 15 or 96 days of vision through both eyes (reopening). One other monkey was monocularly deprived from birth to 189 days. In most cases the behaviour of the ocular dominance stripes formed by the initially closed eye was studied. After 24 days of monocular deprivation from birth, the input from the normal eye was distributed uniformly within layer IV c, with no periodicity evident. After 21 days of deprivation, the deprived eye’s input formed narrow stripes occupying about 38% of layer IV c in the operculum. Seven months of monocular deprivation reduced this to about 29%. Opening the closed eye after the deprivation produced no change in the area innervated: when periods of 15 or 96 days of binocular vision followed the deprivation, the areas innervated by the initially deprived eye were 26 and 30% respectively. However, in both cases the deprived eye’s input formed blobs and spots, rather than uniformly narrow stripes. In contrast to reopening, reverse suturing increased the fraction of layer IV c occupied by input from the initially deprived eye. In the operculum, the effects of reverse suturing appeared to be fully developed after only 6 days of reversal: the initially deprived eye’s stripes having expanded to occupy about 50% of layer IV c. A further 9 days’ reversal produced little change in this. In the visual cortex in the calcarine fissure, the effect of the initial deprivation was more severe, and the expansion induced by reverse suturing more pronounced. The initial deprivation caused the stripes to shrink to occupy 24% of layer IV c; after 6 days of reverse suture the proportion increased to 52%, while after 15 days of reverse suture about 88% of IV c was occupied. These results show that reverse suturing can cause fresh growth of afferent axons in regions of layer IV c from which they had been at least partially removed, either by the normal process of segregation, or as a consequence of monocular deprivation. Taken in conjunction with the findings of the accompanying two papers (Blakemore et al . 1981; Garey & Vital-Durand 1981) they also suggest ( a ) that there is a close relationship between the extent of layer IV c innervated and cell size in the lateral geniculate nucleus, and ( b ) that many of the physiological consequences of deprivation experiments are secondary to anatomical changes in the distribution of afferents from the lateral geniculate nucleus.

The Lines of Evolution of the Bacillariophyta. I. Origin

Abstract: The evolution of the diatoms has never been considered in any detail and this paper sets out some of the problems and discusses briefly the fossil evidence, the likelihood of monophyletic versus polyphyletic origin and the possible habitats of the ancestral forms. We assume that diatoms arose at a fairly early period and certainly long before the Cretaceous, when the first fossil diatoms were deposited. A ‘pre-diatom’ stage is envisaged during which a naked photosynthetic cell acquired a coating of siliceous scales. This was followed by an ‘Ur-diatom’ stage when the siliceous scales differentiated to form valves and girdle bands, to give a recognizable but extremely simple diatom. Evidence for such development is indirect and we discuss this from the standpoint of the structure of scales of modern diatom auxospores, symmetry of initial valves, homology of valves and girdle bands, comparative morphology of auxospore scales/valves/girdle bands and the developmental sequences of modern diatom valve formation. From a discussion of the available data and leaning heavily on electron microscope studies we suggest that there is very considerable evidence to substantiate our hypothesis.

Crystalline A-dna: the X-ray analysis of the fragment d(G-G-T-A-T-A-C-C).

Abstract: An A-DNA type double helical conformation was observed in the single crystal X-ray structure of the octamer d(G-G-T-A-T-A-C-C), 1, and its 5-bromouracil-containing analogue, 2. The structure of the isomorphous crystals (space group P6$_{1}$) was solved by a search technique based on packing criteria and R-factor calculations, with use of only low order data. At the present stage of refinement the R factors are 31% for 1 and 28% for 2 at a resolution of 2.25 angstrom (0.225 nm). The molecules interact through their minor grooves by hydrogen bonding and base to sugar van der Waals contacts. The stable A conformation observed in the crystal may have some structural relevance to promoter regions where the T-A-T-A sequence is frequently found.

Merkel Cells as Targets of the Mechanosensory Nerves in Salamander Skin

Abstract: Previous investigations showed that the morphological basis of the low-threshold rapidly adapting mechanoreceptors in the salamander skin is the neurite--Merkel cell complex located in the epidermis. We have now examined whether sensory nerves are required for the appearance of Merkel cells, and whether these cells act as specific targets for ingrowing sensory axons. Electronmicroscopic examination of denervated skin shows that Merkel cells survive in normal density and appearance in the epidermis for at least six months without nerves. In addition, mechanosensory function of such skin is restored when the skin becomes reinnervated either by collaterally sprouting (intact) nerves or by regenerating ones, and Merkel cells are then found to have nerve terminals associated with them. These experiments suggest that Merkel cells do act as targets for ingrowing nerves in these circumstances. Further experiments were done on skin that had regenerated in the total absence of any innervation to the limb; such new skin contained nerve-free Merkel cells that were normal in appearance, density and location. When nerves were allowed to innervate this new skin the sensory axons grew to the `new9 Merkel cells and established typical neurite--Merkel cell complexes, and normal mechanosensory function. Since the new skin had developed without nerves, the sensory axons were not following `old9 pathways to the Merkel cells. We conclude that the Merkel cells are the true targets for the mechanosensory axons; these cells attract the sensory axons to them and/or contain specific markers that allow the ingrowing axons to recognize them. Once a Merkel cell becomes innervated it loses this `target cell9 quality. In addition, mechanosensory function of the sensory endings appears to occur only when the endings have developed a morphological association with a Merkel cell.

Review Lecture: Neural Mechanisms of Learning: An Analysis of Imprinting in the Domestic Chick

Abstract: Learning is a complex set of processes involving the acquisition and storage of information. Imprinting in the domestic chick was studied to analyse the neural basis of storage. The recently hatched chick learns the characteristics of a visually conspicuous object by being exposed to it. When a chick is trained in this way, biochemical changes can be detected in the dorsal part of the forebrain. Through a series of experiments it was shown that these changes are unlikely to be non-specific consequences of training, but more probably reflect some aspect of the storage process. By using a radioautographic technique to localize the brain region more precisely, part of the hyperstriatum ventrale was implicated in this process. Bilateral destruction of the region before imprinting prevented acquisition, and bilateral destruction after imprinting impaired retention. After exposure for 140 min to an imprinting stimulus there was an increase in the area of contact between presynaptic and postsynaptic elements in the region. This effect was found on the left side only. Sequential lesions to left and right sides confirmed that there is a hemispheric asymmetry in the role of the region in the storage of information. The area receives input from the visual pathways and possibly from other sensory pathways, and projects to regions that are thought to be involved in the control of locomotor and viscero-endocrine functions. The results afford an opportunity for the further analysis both of storage and of the whole set of neural processes that underlie imprinting in the domestic chick.U

Patterns in the discharge of simple and complex visual cortical cells

Abstract: The activity of visual cortical neurons (area 17) was recorded in anaesthetized cats in response to sinusoidal drifting gratings. The statistical structure of the discharge of simple and complex cells has been studied as a function of the various parameters of a drifting grating: spatial frequency, orientation, drifting velocity and contrast. For simple cells it has been found that the interspike interval distributions in response to drifting gratings of various spatial frequencies differ only by a time scale factor. They can be reduced to a unique distribution by a linear time transformation. Variations in the spatial frequency of the grating induce variations in the mean firing rate of the cell but leave unchanged the statistical structure of the discharge. On the contrary, the statistical structure of simple cell activity changes when the contrast or the velocity of the stimulus is varied. For complex cells it has been found that the invariance property described above for simple cells is not valid. Complex cells present in their activity in response to visual stimuli two different firing patterns: spikes organized in clusters and spikes that do not show this organization (`isolated spikes'). The clustered component is the only component of the complex cell discharge that is tuned for spatial frequency and orientation, while the isolated spike component is correlated with the contrast of the stimulus.

Calcium Transients Recorded with Arsenazo III in the Presynaptic Terminal of the Squid Giant Synapse

Abstract: Transient changes in free intracellular Ca$^{2+}$ concentration were monitored in the presynaptic terminal of the giant synapse of the squid, by means of the Ca$^{2+}$-sensitive dye arsenazo III. Calibration experiments showed a linear relation between the amount of Ca$^{2+}$ injected by iontophoresis into the terminal, and the peak size of the arsenazo light absorbance record. A light signal could be detected on tetanic stimulation of the presynaptic axon bathed in sea water containing 45 mM Ca$^{2+}$. During a 1 s tetanus the light signal rose approximately linearly, even though transmitter release declined rapidly and the light signal subsequently declined with a half-time of 2-6 s. The Ca$^{2+}$ transient elicited by single nerve impulses was recorded by signal averaging, and showed a time course very much slower than the duration of transmitter release.

Evolution of recombination in populations experiencing frequency-dependent selection with time delay

Abstract: This paper proposes a model for the evolution of recombination. The model is based on the notion that when a species (say species 1) interacts with other antagonistic species, species 1 will act as a selective force on them, favouring antagonists best able to destroy its most frequent phenotypes. Only if the progeny of these phenotypes are different from their parents are they able to escape the full force of selected antagonists. A deterministic haploid genetic model with two linked loci and a third unlinked recombination-modifying locus is constructed, using frequency-dependent selection with time delay, to describe the effects of antagonists. Analysis of the model shows that a modifier mutant causing recombination usually starts to spread into a population without recombination, and under certain conditions can spread even if there is already some recombination in the population. The relevance of these results to observations of recombination in the natural world is discussed.

The sizes of motoneurons supplying hindlimb muscles in the mouse

Abstract: Motoneurons supplying identified muscle groups in the mouse spinal cord were labelled by retrograde transport of horseradish peroxidase. The size of motoneurons was estimated by measuring perimeter and cross-sectional area at the level of the nucleolus for the following seven major muscle groups: quadriceps femoris, adductors and gracilis, gluteal musculature, hamstring muscles, posterior crural musculature, anterolateral crural musculature and intrinsic musculature of the foot. The qualitative observation of two size ranges of motoneuron was supported by the measurements. Frequency distribution histograms of motoneuronal cross sectional area were bimodal for all motoneuronal groups except for the foot musculature. The population parameters and proportions for the six bimodal histograms were estimated by the method of maximum likelihood. It was found that the mean area of the small neuron component, which were presumed to be gamma motoneurons, was similar for the six bimodal systems. In contrast to this the mean area of the large neuron component, presumed to be alpha motoneurons, was found to be different for the six bimodal systems; motoneurons supplying more proximal muscles showed a larger mean area than those supplying distal muscles. The mean area of both components was unaffected by survival time and this was interpreted as indicating that changes in survival time did not label greater numbers of small or large motoneurons. The proportion of motoneurons in the small neuron component was found to vary from 9 to 27%.

Enzymic editing mechanisms and the genetic code.

Abstract: The evolution of stable forms of life requires considerable precision in the transfer and utilization of genetic information. The necessary precision is often beyond the limits of even the high specificity expected of enzymes and has been achieved by the coevolution of special enzymic mechanisms that involve the expenditure of some of the energy of the cell. The exquisite fidelity of the genetic coding process is maintained during the replication of DNA and the synthesis of proteins by editing reactions that remove errors. Without these checks, mutation rates would be unacceptably high and proteins largely heterogeneous. The editing mechanisms of amino acid selection during protein synthesis are discussed and used to exemplify the essential features of editing. An incidental result of these studies has been to reveal unexpectedly high binding energies between the side chains of amino acids and the enzymes responsible for their selection. This necessitates a re-evaluation of the forces responsible for the folding and assembly of proteins. The fidelity of DNA replication is now amenable to study by a combination of kinetic and genetic techniques by replicating in vitro DNA from a bacteriophage ($\phi $X174) and assaying the products by expression in vivo. This has afforded the first measurements of the nature and frequency of the base mispairings that lead to spontaneous mutation. These indicate that the accuracy of Escherichia coli DNA polymerase is the limiting factor determining the rate of spontaneous mutation of the single-stranded DNA bacteriophage. The more accurate replication of the E. coli chromosome requires a post-replicative mismatch repair system, special to double-stranded DNA. A simple relation between the accuracy gained by editing and the cost in terms of the wasteful hydrolysis of the correct products, the cost-selectivity equation, is presented that rationalizes some of the mechanisms and observations.

Structure and Development of the Apical Organ in Trochophores of Spirobranchus polycerus, Phyllodoce maculata and Phyllodoce mucosa (Polychaeta)

Abstract: The apical organ of a typical serpulid trochophore (Spirobranchus) and of the more complex trochophore larva of Phyllodoce are described on the basis of ultrastructural surveys and three-dimensional reconstructions. A plexus-like structure formed by vesicle-filled processes from certain of the apical cells is shown to be an integral part of the apical organ in both genera, persisting in Phyllodoce long after the regression of the external apical tuft. Because of its central position and early development, the plexus may play an important role in the development and functioning of the larval nervous system as a whole. With regard to its developmental role, morphological evidence supports the hypothesis that the plexus serves as an initial target for growing neurites responsible in part for establishing the path along which the cerebral commissure later develops. The constituent cells of the apical organ in Spirobranchus are catalogued as to type and position, including cells associated with the entry of nerves into the apical plexus. Constancy from larva to larva is shown to be greatest for the eight most apical cells, comprising two ciliated cells, one of which is responsible for the apical tuft, three plexus cells, and three capsular cells. There are clear parallels between Spirobranchus and Phyllodoce in the arrangement of apical cells, suggestive of a common plan, and the probable origin of this arrangement in terms of cell lineage is discussed.

Concerning the form of biochemically active vanadium.

Abstract: A survey has been made of the descriptive chemistry of vanadium as it pertains to physiological environments. Taking into account the vanadium concentration, pH, coordinating ligands and chelates, presence of other cations, oxidation-reduction potentials and the kinetics of the various vanadium-containing species, the following suggestions are made. Free vanadium ions will be monomeric. Monomeric vanadium(V) and vanadium(IV) will each exist in a specific hydrated form. Extracellular vanadium will be in the vanadate, Vv, form. Intracellular vanadium will most likely be predominantly in the vanadyl, Viv, form. Both extracellular vanadium(V) and intracellular vanadium(IV) will be bound to bi- or tridentate ligands if at all. If oxidation-reduction processes involving vanadium are fast relative to transmembrane transport, the transmembrane potential will not be coupled to the Vv/Viv Nernstian potential.

The Bakerian Lecture, 1981: Natural Selection of the Chemical Elements

Abstract: Biochemistry is the study of an intricate interwoven \`designed' use of many elements in cells. It can only be fully appreciated in terms of the patterns of flow of chemicals, of ionic and electronic charge, and of energy directed in space. This requires a knowledge of the selection of the elements not only in analytical terms of uptake and chemical combination but also in terms of their spatial separation and functional specification. Starting from the abundance and availability of the elements an attempt is made here to analyse the roles of the elements, showing that much of the \`chosen' chemistry is an inevitable consequence of atomic properties. Selection has played upon this chemistry, extracting the utmost value from it, as seen in the refinement of functions of individual elements so that each element plays a quite separate and distinct role. Unique qualities dominate comparative similarities through the use of evolved specific small molecule and protein ligands. Proteins provide the evolutionary media for the development of function. It was the recognition and separation of each element in their specific sites (proteins) that allowed elements to be positioned in space. In turn the spatial organization generates, through feedback, the flow of other elements. Biological chemistry is only understandable in terms of the symbiotic use of some 25 elements and should not be related to so-called organic rather than to so-called inorganic chemistry.