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Biomedical subjects

R V Stirling

Publications and source records attributed to R V Stirling.

At least 19 recordsLinked to original sources
PubMed2003

Training on a visual task improves the outcome of optic nerve regeneration.

Optic nerve regeneration in a lizard, Ctenophorus ornatus, is dysfunctional despite survival of most retinal ganglion cells and axon regeneration to the optic tectum. The regenerated retino-tectal projection at 6 months has crude topography but by 1 year is disordered; visually-elicited behavior is absent via the experimental eye. Here, we assess the influence of training on the outcome of optic nerve regeneration. Lizards were trained to catch prey presented within the monocular field of either eye. One optic nerve was then severed and visual stimulation resumed throughout regeneration. In the trained group, presentation was restricted to the eye undergoing optic nerve regeneration; for the untrained group, the unoperated eye was stimulated. Pupil responses returned in trained but not in untrained animals. At 1 year, trained animals oriented to and captured prey; untrained animals demonstrated minimal orienting and failed to capture prey. Regenerated retino-tectal projections were topographic in the trained but not in the untrained group as assessed by in vitro electrophysiological recording and by carbocyanine dye tracing. In vitro electrophysiological recording during application of neurotransmitter antagonists to the tectum revealed that the level of GABAergic inhibition was modest in trained animals but elevated in the untrained group; responses were mainly AMPA-mediated in both groups. We conclude that training improves the behavioral outcome of regeneration, presumably by stabilizing and refining the transient retino-tectal map and preventing a build-up of tectal inhibition. The results suggest that for successful central nerve regeneration to occur in mammals, it may be necessary to introduce training to complement procedures stimulating axon regeneration.

Animals↗
PubMed2001

Continued neurogenesis is not a pre-requisite for regeneration of a topographic retino-tectal projection.

Electrophysiological recording demonstrated that visuo-tectal projections are topographically organised after optic nerve regeneration in aged Xenopus laevis. 3H-thymidine autoradiography confirmed previous reports [Taylor, Lack, & Easter, Eur. Journal of Neuroscience 1 (1989) 626-638] that cell division had already ceased at the retinal ciliary margin. The results demonstrate that, contrary to a previous suggestion [Holder & Clarke, Trends in Neuroscience 11 (1988) 94-99], continued neurogenesis is not a pre-requisite for the re-establishment of appropriate connections with target cells.

Aging↗
PubMed1998

An in vitro technique for electrophysiological mapping of reptilian retinotectal projections.

An in vitro procedure is described for electrophysiological mapping of the retinotectal projections using an eye-cup and brain stem preparation which remains viable for up to 30 h. The technique has been found to be successful in turtles and lizards and may be useful for other species in which metabolism is greatly depressed by low temperatures. There are several advantages over in vivo recording, including the longevity and stability of the preparation, an absence of confounding anaesthetic effects and the ability to record from the retina as well as from the brain. The technique offers opportunities to introduce pharmacological agents via the perfusate or to conduct anatomical tracing studies coincident with electrophysiological recording.

Animals↗
PubMed1998

Development of muscle afferents in the spinal cord of the tammar wallaby.

The development of muscle afferents in the tammar wallaby was examined to address whether proprioceptive input contributes to the marked asymmetry of the fore and hindlimb movement. Anatomical tracing with biocytin showed that the muscle afferents had reached the brachial motor horn by postnatal day (P1), but were less advanced in the lumbar region. Labelled cells lying outside the motor horn, presumably filled via gap junctions, were evident in the neonatal lumbar cord. By the 4th postnatal week, the afferent innervation of both brachial and lumbar cords became similar. Afferent discharges from stretching the biceps muscle could be recorded at birth, but not until P4 from the hindlimb gastrocnemius muscle. The discharges were predominantly phasic until P35 when tonic activity could also be recorded. Short latency spinal reflex responses superimposed upon a longer lasting potential were present in the brachial cord at birth, appearing in the lumbar cord at P4. By the 3rd postnatal week, spinal reflex became comparable in both segmental levels. The time course of muscle afferent development was compared to the progression of natural cell death in the lumbar cord. Sensorimotor connections were established towards the end of the rapid phase cell death as observed in other vertebrates.

Action Potentials↗
PubMed1995

The segmental precision of the motor projection to the intercostal muscles in the developing chicken embryo. A differential labelling study using fluorescent tracers.

Each skeletal muscle in the vertebrate is innervated by a group of motoneurons called a motoneuron pool. Retrograde labelling of single motoneuron pools has suggested that the arrangement of motoneuron pools innervating different limb muscles does not change during the embryonic period when more than 50% of the motoneurons die. In this study we retrogradely labelled neighbouring intercostal motoneuron pools differentially with latex microspheres or dextran amines coupled to fluorescent dyes. We then mapped the positions of the differentially labelled motoneurons in whole-mount preparations using a computer-aided drawing system. While the intercostal motoneuron pools are clearly segregated even at early stages, there is some intermingling at the rostral and caudal ends. We used a logistic regression to determine the extent of segmental overlap, and to facilitate a quantitative comparison of the overlap at different stages. Statistical analysis shows that the overlap (expressed as the percentage of the length of the overlapping motoneuron pools) decreases modestly during the period of motoneuron death. Computer simulations suggest that this decrease does not result from random motoneuron death alone; one alternative possibility is selective death of motoneurons in the overlap zone. Occasional "rogue" motoneurons, that is, motoneurons of one pool that scatter into the neighbouring pool, are still present at the end of the period of cell death, representing a potential source of "noise" in the establishment of segmental patterns of connectivity.

Animals↗
PubMed1995

The dance of the growth cones--where to next?

Axon guidance in the developing nervous system is accomplished by a remarkable structure, the axon growth cone. This structure navigates, often over long distances, to find and synapse with target cells. Transformation of the growth cone to a terminal arbor establishes functional circuitry. The navigational properties of growth cones, and their interactions with target tissue, have been studied widely by examining individual cells in vitro, and have also been inferred from histological sections. Recent advances in labelling techniques and imaging of living cells have enabled direct observation of the growing axon tip in intact embryos as well as in slice preparations. To understand how pathways and terminal arbors are formed, the challenge now is to relate the dynamic morphology and behaviour of living growth cones to surrounding cues in the complex environment of the developing embryo.

Animals↗
PubMed1988

Specific guidance of motor axons to duplicated muscles in the developing amniote limb.

The effect of alteration of limb pattern upon motor axon guidance has been investigated in chick embryos. Following grafting of the zone of polarizing activity (ZPA) into the anterior margin of the early limb bud, limbs develop with forearms duplicated about the anteroposterior axis. The position of motoneurones innervating the duplicated posterior forearm extensor EMU was mapped by retrograde transport of horse radish peroxidase (HRP). The motor pool labelled from injection into the anteriorly duplicated EMU muscle is consistently similar to that supplying the posterior EMU muscle on the unoperated side of the embryo. In those cases where the axons are well filled, their trajectories from the injection site are observed to change position within the radial nerve to specifically innervate the duplicated muscle. The axons modify their trajectories proximal to the level of limb duplication in a region where there is no change in the pattern of overt differentiation of the limb cells. This suggests that axons may use a cell's positional value to navigate and provides significant support for the theory of positional information.

Animals↗
PubMed1987

Functional morphology of frog retinal ganglion cells and their central projections: the dimming detectors.

Intracellular recordings were made from frog retinal ganglion cell axons in the optic nerve. Following electrophysiological characterisation of receptive field properties, HRP was injected into the axon, and the brain and retina were subsequently stained. The morphologies of retinal ganglion cells, their dendritic domains, and their central projections were determined with light microscopy, and the optic nerve portion of the ganglion cell axon was examined with electron microscopy. This paper describes the structural and functional features of one ganglion cell class, the off units (class IV or dimming detectors) whose characteristic response is a preferential sensitivity to decreasing light intensity within the receptive field. Typical receptive field diameter of these units was about 16 degrees with a range of 3 degrees to more than 30 degrees. Examination of the spatial characteristics of their receptive field centers and surrounds showed that the class IV cells could be divided into two broad categories. Linear class IV cells did not respond to phase-reversal of a fine grating pattern. These linear cells also tended to have clear surround suppression: illumination of the surround diminished their response to light off at the center. The second group responded briskly to each reversal of the fine grating pattern, whatever its position within the receptor field center. These nonlinear class IV cells did not show surround suppression, but rather they had surround antagonism and they responded to light on in the surround. Nonlinear units were much more frequently recorded in frogs maintained in summer conditions (12-hour days, constant 20 degrees C temperature). In spite of this functional heterogeneity, all cells had similar morphology consisting of a large ganglion cell with a large dendritic arbor (400-1,000 microns) confined to a single stratum in the outer third of the inner plexiform layer, a medium-sized axon (2.4-microns diameter), a smallish pretectal arbor, and a large tectal arbor (300-700 microns) at layer 8.

Animals↗
PubMed1987

The specificity of motor innervation of the chick wing does not depend upon the segmental origin of muscles.

In vertebrate embryos, motor axons originating from a particular craniocaudal position in the neural tube innervate limb muscles derived from myoblasts of the same segmental level. We have investigated whether this relationship is important for the formation of specific nerve-muscle connections, by altering the segmental origin of muscles and examining their resulting innervation. First, by grafting quail wing somites to a new craniocaudal position opposite the chick wing, we established that the segmental origin of a muscle can be altered: presumptive muscle cells migrated according to their new, rather than their original, somitic level, colonizing a different subset of muscles. However, after reversal of a length of brachial somitic mesoderm along the craniocaudal axis, or exchange or shift of brachial somites, the craniocaudal position of wing muscle motoneurone pools within the spinal cord was undisturbed, despite the new segmental origin of the muscles themselves. While not excluding the possibility that muscles and their motor nerves are labelled segmentally, we conclude that specific motor axon guidance in the wing does not depend upon the existence of such labels.

Animals↗
PubMed1985

The behaviour of growing axons invading developing chick wing buds with dorsoventral or anteroposterior axis reversed.

The trajectories of motor axons innervating chick wings reversed about the DV or AP axis before axon invasion were analysed after retrograde filling by HRP injection into biceps or triceps muscles. Chick-quail chimaeras showed that the plane of reversal for flank operations was proximal to the confluence of the 14th, 15th, and 16th spinal roots as they form the plexus. The shoulder reversal plane was distal to the plexus. In dorsoventral (DV) reversed wings at both shoulder or flank level, the motor axons do not alter their course as they enter the graft. They therefore innervate by passive deployment any target that they encounter. In anteroposterior (AP) reversed wings at both shoulder or flank level, the motor axons clearly corrected their position in the nerve tract after entering the graft and innervated appropriate targets. The innervation of appropriate targets in AP shoulder reversals shows that axons are sensitive to AP mismatch distal to the plexus. Since axons were displaced similar distances from their normal routes in flank DV and AP reversals, the difference in behaviour suggests that they respond to mismatch in the AP but not the DV axis.

Animals↗
PubMed1982

Expansion of the visual projection to the tectum of axolotls during metamorphosis.

During artificially induced metamorphosis in axolotls, the indirect visual projection from the ipsilateral eye develops followed by the expansion of the contralateral direct projection to occupy most of the tectal surface. During expansion the ipsilateral input is temporarily lost indicating the functional interdependence of the two projections. Final stabilization of the projections and congruence of the ipsilateral and contralateral inputs is achieved a month after arrival on land.

Ambystoma↗
PubMed1981

The innervation of dorsoventrally reversed chick wings: evidence that motor axons do not actively seek out their appropriate targets.

In normal chick embryos the extensor (dorsal) muscles are innervated by motoneurones lying laterally in the motor horn, while flexor muscles are supplied by more medially placed motoneurones. After reversal of the dorsoventral axis of the forelimb prior to innervation in most cases the opposite pattern is found, the extensors innervated by medial and flexors by lateral motor neurones. In a minority of cases the normal innervation pattern is obtained. Three hypotheses are discussed, two involving specific target affinity between motor axon and target and one involving passive deployment of axons to targets. We conclude that our results favour the latter hypothesis but that we cannot exclude a short-range specific signal.

Animals↗
PubMed1979

The central pathways of optic fibres in Xenopus tadpoles.

A cobalt chloride impregnation technique was applied to the optic nerve in Xenopus tadpoles and the central optic pathways were examined in cleared, whole-mounted preparations, and in thick sections. The overall plan of the optic input was visualized in relation to the outlines of the parts of the brain and details of the structure of the tectal optic neuropil, the neuropil of Bellonci and the basal optic neuropil were seen. The fibres in the main retinotectal tract maintained an orderly disposition with respect to each other, in contrast to the fibres of the basal optic tract, in which no order was apparent. Optic fibres were seen passing caudally from the region of the basal optic neuropil.

Animals↗
PubMed1978

Observations on the commissural projection to the dentate gyrus in the Reeler mutant mouse.

The commissural projection to the displaced granule cells of the dentate gyrus in Reeler mutant mice has been examined with autoradiography, and light and electron microscopy. Commissural terminals in Reeler are confined to the hilar region, in contrast to normal littermates in which this projection is restricted to the inner part of the molecular layer. Granule cell somata in Reeler, but only exceptionally in normal littermates, are invested with spines, which have postsynaptic specializations, but no spine apparatus, and are contacted by presynaptic terminals. Between 20 and 30 h after destruction of the commissural fibres in Reeler, degenerating terminals can be found contacting both somatic and dendritic spines in the hilus; 30 h after decommissuration the number and length of spines on the somata and proximal dendrites of Golgi impregnated cells is greatly reduced, while spines on the distal parts of the dendritic tree are unaffected. A similar pattern of degeneration after decomissuration is found in the inner molecular layer of normal littermates. These results are discussed in terms of factors controlling the normal development of afferent projections. The paper concludes with an analysis of a potential methodological hazard. A change in mean spine length will of itself result in a change in the number of visible spines in golgi material. A quantitative assessment of the relation between spine length and the number of visible spines is developed for spherical cell bodies and cylindrical dendrites.

Animals↗