Temporal hyperacuity in single neurons of electric fish

Behavioural studies have revealed that animals can resolve temporal disparities in the microsecond range. This resolution is far superior to that of individual receptors, and it must therefore be achieved through central neuronal mechanisms. It is unclear, however, whether such sensitivity ever emerges at the level of single neurons, or whether it is apparent only at the behavioural level through the collective action of many less-sensitive neurons. We have found that single neurons in the pre-pacemaker nucleus of a weakly electric fish are sensitive to temporal disparities as small as 1 microsecond, the highest temporal sensitivity ever observed at the single-neuron level. The remarkable temporal resolution of these pre-pacemaker neurons results from a high degree of spatial convergence of afferent inputs. These neurons represent the final elements of a sensory hierarchy and directly control the jamming avoidance response by which these fish regulate the frequency of their electric organ discharges.     

Prenatal development of individual retinogeniculate axons during the period of segregation

When connections are first formed during the development of the vertebrate nervous system, inputs from different sources are frequently intermixed and the specific adult pattern then emerges as the different inputs segregate from each other. During the prenatal development of connections between retina and lateral geniculate nucleus (LGN) in the cat, the projections from the two eyes initially overlap with each other within the LGN. Over the next 3 weeks a reduction in the amount of overlap occurs so that by birth, a segregated pattern similar to the adult is present. We report here that during the period of overlap, individual retinogeniculate axons are simple in shape and restricted in extent without any widespread branches. Further, the appearance of the segregated pattern of eye input is accompanied by the elaboration of extensive new axonal arbors within appropriate LGN territory accompanied by retraction of only a limited number of minor branches. This developmental strategy contrasts with that in other regions of the vertebrate central nervous system in which the orderly adult pattern of connections within a target is achieved by a relative reduction in the overall extent of the axon arbor.     

Motion-deblurring in human vision

If photographs are taken of moving objects at slow shutter speeds the images of the objects are blurred. In human vision, however, we are not normally conscious of blur from moving objects despite the fact that the temporal response of the photoreceptors is sluggish. It has been suggested that there are motion-deblurring mechanisms specifically to aid the visual system in the analysis of the shape of retinally moving targets. Models of motion deblurring have been influenced by the finding that certain very precise spatial pattern discriminations are unaffected by motion. An example is vernier hyperacuity, in which the observer must detect the direction of offset between two lines with abutting ends. With a stationary stimulus, observers can detect a vernier cue of less than 10 arcsec and acuity is unaffected by retinal-image motion of up to 3 deg s-1 We confirm this finding, but provide evidence against any general deblurring mechanism by showing that another kind of hyperacuity, discrimination of the distance between two parallel lines (spatial interval acuity), is interfered with by motion. This argues against a general deblurring mechanism, such as a neural network 'shifter circuit', and we point out that the high level of vernier acuity for moving stimuli is susceptible to an alternative explanation.     

The role of nonlinear dynamics of the syrinx in the vocalizations of a songbird

Birdsong is characterized by the modulation of sound properties over a wide image of timescales. Understanding the mechanisms by which the brain organizes this complex temporal behaviour is a central motivation in the study of the song control and learning system. Here we present evidence that, in addition to central neural control, a further level of temporal organization is provided by nonlinear oscillatory dynamics that are intrinsic to the avian vocal organ. A detailed temporal and spectral examination of song of the zebra finch (Taeniopygia guttata) reveals a class of rapid song modulations that are consistent with transitions in the dynamical state of the syrinx. Furthermore, in vitro experiments show that the syrinx can produce a sequence of oscillatory states that are both spectrally and temporally complex in response to the slow variation of respiratory or syringeal parameters. As a consequence, simple variations in a small number of neural signals can result in a complex acoustic sequence.     

Evidence for a central component of post-injury pain hypersensitivity

Noxious skin stimuli which are sufficiently intense to produce tissue injury, characteristically generate prolonged post-stimulus sensory disturbances that include continuing pain, an increased sensitivity to noxious stimuli and pain following innocuous stimuli. This could result from either a reduction in the thresholds of skin nociceptors (sensitization) or an increase in the excitability of the central nervous system so that normal inputs now evoke exaggerated responses. Because sensitization of peripheral receptors occurs following injury, a peripheral mechanism is widely held to be responsible for post-injury hypersensitivity. To investigate this I have now developed an animal model where changes occur in the threshold and responsiveness of the flexor reflex following peripheral injury that are analogous to the sensory changes found in man. Electrophysiological analysis of the injury-induced increase in excitability of the flexion reflex shows that it in part arises from changes in the activity of the spinal cord. The long-term consequences of noxious stimuli result, therefore, from central as well as from peripheral changes.     

Developmental genetics of vertebrate glial-cell specification

Oligodendrocytes and astrocytes are macroglial cells of the vertebrate central nervous system. These cells have diverse roles in the maintenance of neurological function. In the embryo, the genetic mechanisms that underlie the specification of macroglial precursors in vivo appear strikingly similar to those that regulate the development of the diverse neuron types. The switch from producing neuronal to glial subtype-specific precursors can be modelled as an interplay between region-restricted components and temporal regulators that determine neurogenic or gliogenic phases of development, contributing to glial diversity. Gaining insight into the developmental genetics of macroglia has great potential to improve our understanding of a variety of neurological disorders in humans.     

Central inputs mask multiple adult neural networks within a single embryonic network

It is usually assumed that, after construction of basic network architecture in embryos, immature networks undergo progressive maturation to acquire their adult properties. We examine this assumption in the context of the lobster stomatogastric nervous system. In the lobster, the neuronal population that will form this system is at first orgnanized into a single embryonic network that generates a single rhythmic pattern. The system then splits into different functional adult networks controlled by central descending systems; these adult networks produce multiple motor programmes, distinctively different from the single output of the embryonic network. We show here that the single embryonic network can produce multiple adult-like programmes. This occurs after the embryonic network is silenced by removal of central inputs, then pharmacologically stimulated to restore rhythmicity. Furthermore, restoration of the flow of descending information reversed the adult-like pattern to an embryonic pattern. This indicates that the embryonic network possesses the ability to express adult-like network characteristics, but descending information prevents it from doing so. Functional adult networks may therefore not necessarily be derived from progressive ontogenetic changes in networks themselves, but may result from maturation of descending systems that unmask preexisting adult networks in an embryonic system.     

血脑屏障和中枢神经系统疾病相关性的研究进展

中枢神经系统接受全身各处的传入信息, 经中枢神经系统整合加工后成为协调的运动传出, 或者储存在中枢神经系统内成为学习、记忆的神经基础. 中枢神经系统易受到致病因素影响而发生以精神活动障碍为主要表现的疾病, 同时亦可出现中枢神经系统退行性病变. 而血脑屏障能够使脑组织少受甚至不受循环血液中有害物质的损害, 从而保持脑组织内环境的基本稳定, 对维持中枢神经系统正常生理状态具有重要的生物学意义. 对血脑屏障与中枢神经系统疾病相关性的研究进展进行总结与综述, 以期为中枢神经系统疾病的预防与治疗提供更新与更全面的理论基础.     

Peripheral nerve injury triggers central sprouting of myelinated afferents.

The central terminals of primary afferent neurons are topographically highly ordered in the spinal cord. Peripheral receptor sensitivity is reflected by dorsal horn laminar location: low-threshold mechanoreceptors terminate in laminae III and IV (refs 2, 3) and high-threshold nociceptors in laminae I, II and V (refs 4,5). Unmyelinated C fibres, most of which are nociceptors, terminate predominantly in lamina II (refs 5, 7). There is therefore an anatomical framework for the transfer of specific inputs to localized subsets of dorsal horn neurons. This specificity must contribute to the relationship between a low-intensity stimulus and an innocuous sensation and a noxious stimulus and pain. We now show that after peripheral nerve injury the central terminals of axotomized myelinated afferents, including the large A beta fibres, sprout into lamina II. This structural reorganization in the adult central nervous system may contribute to the development of the pain mediated by A-fibres that can follow nerve lesions in humans.     

Multiple forms of synaptic plasticity triggered by selective suppression of activity in individual neurons

The rules by which neuronal activity causes long-term modification of synapses in the central nervous system are not fully understood. Whereas competitive or correlation-based rules result in local modification of synapses, homeostatic modifications allow neuron-wide changes in synaptic strength, promoting stability. Experimental investigations of these rules at central nervous system synapses have relied generally on manipulating activity in populations of neurons. Here, we investigated the effect of suppressing excitability in single neurons within a network of active hippocampal neurons by overexpressing an inward-rectifier potassium channel. Reducing activity in a neuron before synapse formation leads to a reduction in functional synaptic inputs to that neuron; no such reduction was observed when activity of all neurons was uniformly suppressed. In contrast, suppressing activity in a single neuron after synapses are established results in a homeostatic increase in synaptic input, which restores the activity of the neuron to control levels. Our results highlight the differences between global and selective suppression of activity, as well as those between early and late manipulation of activity.     

Retinofugal fibres change conduction velocity and diameter between the optic nerve and tract in ferrets

In earlier studies of central nervous fibre tracts, it was tacitly assumed that individual axons are relatively uniform along their length. In the retinofugal pathway in particular, axon diameter, myelin thickness and correlated conduction properties have been treated as constant throughout the optic nerve, chiasm and tract. We report here that the conduction velocities of fibres contributing to the early components of the compound action potential are significantly greater in the optic tract than in the optic nerve of ferrets, and also that the diameters of the largest retinofugal fibres increase from nerve to tract. This observation raises significant questions about the developmental mechanisms in the central nervous system that relate the axons, their diameters, and the glia with which they are myelinated. In addition, it indicates that studies that have relied on the constancy of conduction velocity along the retinofugal course may require reappraisal.     

Miniature eye movements enhance fine spatial detail

Our eyes are constantly in motion. Even during visual fixation, small eye movements continually jitter the location of gaze. It is known that visual percepts tend to fade when retinal image motion is eliminated in the laboratory. However, it has long been debated whether, during natural viewing, fixational eye movements have functions in addition to preventing the visual scene from fading. In this study, we analysed the influence in humans of fixational eye movements on the discrimination of gratings masked by noise that has a power spectrum similar to that of natural images. Using a new method of retinal image stabilization, we selectively eliminated the motion of the retinal image that normally occurs during the intersaccadic intervals of visual fixation. Here we show that fixational eye movements improve discrimination of high spatial frequency stimuli, but not of low spatial frequency stimuli. This improvement originates from the temporal modulations introduced by fixational eye movements in the visual input to the retina, which emphasize the high spatial frequency harmonics of the stimulus. In a natural visual world dominated by low spatial frequencies, fixational eye movements appear to constitute an effective sampling strategy by which the visual system enhances the processing of spatial detail.     

GABA affects the release of gastrin and somatostatin from rat antral mucosa

gamma-Aminobutyric acid (GABA) is regarded as the major inhibitory neurotransmitter in the central nervous system of vertebrates. GABA exerts its inhibitory actions by interacting with specific receptors on pre- and postsynaptic membranes and has been shown to inhibit somatostatin release from hypothalamic neurones in vitro. Concepts of innervation of the gastrointestinal tract have been expanded by recent studies which suggest that GABAergic neurones are not confined solely to the central nervous system but may also exist in the vertebrate peripheral autonomic nervous system. Jessen and coworkers have demonstrated the presence, synthesis and uptake of GABA by the myenteric plexus of the guinea pig taenia coli, and have documented the presence of glutamic acid decarboxylase (GAD) in isolated myenteric plexus. This enzyme is responsible for the conversion of glutamic acid to GABA in GABAergic neurones. The possibility that GABA may have a role in neurotransmission or neuromodulation in the enteric nervous system of the vertebrate gut has been suggested by several investigators. Furthermore, GABA receptors have been demonstrated on elements of the enteric nervous system. The effects of GABA on gastrointestinal endocrine cell function have not been examined. We report here the effects of GABA on gastrin and somatostatin release from isolated rat antral mucosa in short-term in vitro incubations.     

Immunospecific inhibition of nerve conduction by T lymphocytes reactive to basic protein of myelin

Experimental autoimmune encephalomyelitis (EAE) induced by immunization to the basic protein of central nervous system myelin (BP) is a paralytic disease in which T lymphocytes attack the individual's own central nervous system. As the target is in white matter, EAE has been considered an experimental model of some aspects of human disease such as multiple sclerosis. To investigate whether autoimmune T lymphocytes could produce paralysis, we studied the effects on the electrophysiology of isolated nerves produced by T-lymphocyte lines reactive specifically to BP or other antigens. We now report that propagation of action potentials evoked by electrical stimulation was blocked by incubating optic nerves with specific anti-BP T cells. This blockade could be reversed for up to two hours by removing the anti-BP line cells from the optic nerve. The anti-BP line cells had no effect on conduction along allogeneic optic nerves or syngeneic peripheral nerves. This indicates that disruption of the function of myelin in neuroimmunological disease may result from an immunologically specific interaction between autoimmune T lymphocytes and myelin antigens.     

High-fidelity transmission of sensory information by single cerebellar mossy fibre boutons

Understanding the transmission of sensory information at individual synaptic connections requires knowledge of the properties of presynaptic terminals and their patterns of firing evoked by sensory stimuli. Such information has been difficult to obtain because of the small size and inaccessibility of nerve terminals in the central nervous system. Here we show, by making direct patch-clamp recordings in vivo from cerebellar mossy fibre boutons-the primary source of synaptic input to the cerebellar cortex-that sensory stimulation can produce bursts of spikes in single boutons at very high instantaneous firing frequencies (more than 700 Hz). We show that the mossy fibre-granule cell synapse exhibits high-fidelity transmission at these frequencies, indicating that the rapid burst of excitatory postsynaptic currents underlying the sensory-evoked response of granule cells can be driven by such a presynaptic spike burst. We also demonstrate that a single mossy fibre can trigger action potential bursts in granule cells in vitro when driven with in vivo firing patterns. These findings suggest that the relay from mossy fibre to granule cell can act in a 'detonator' fashion, such that a single presynaptic afferent may be sufficient to transmit the sensory message. This endows the cerebellar mossy fibre system with remarkable sensitivity and high fidelity in the transmission of sensory information.     

Synaptic connections between different sensory channels in CNS of the leech modulate the input of mechanosensory information

The mechanism for transmission of sensory information concerning a specific sensory modality or submodality can be called a sensory channel, including the receptors, sensory pathways and the parts of the central nervous system that further process the sensory information^[1,2]. A certain sensory channel can be activated by a suitable stimulus. Saraory infonnation is traduced by sensory receptor and is further transferred into central nervous system. The characteristics of a modality or submodality are meinly determined by the properties of the corresponding sensory receptors. However, besides the receptor properties, are there any other factors which have influence on the properties of a senwry modality? Is there a kind of gating mechanism existing which could selectively control the inputs of sensory information based on different sensory channels? Here we are trying to answer the above questions by studying the functional relationship between different mechanosensory modalities of leech.     

Molecular cloning and expression of brain-derived neurotrophic factor

During the development of the vertebrate nervous system, many neurons depend for survival on interactions with their target cells. Specific proteins are thought to be released by the target cells and to play an essential role in these interactions. So far, only one such protein, nerve growth factor, has been fully characterized. This has been possible because of the extraordinarily (and unexplained) large quantities of this protein in some adult tissues that are of no relevance to the developing nervous system. Whereas the dependency of many neurons on their target cells for normal development, and the restricted neuronal specificity of nerve growth factor have long suggested the existence of other such proteins, their low abundance has rendered their characterization difficult. Here we report the full primary structure of brain-derived neurotrophic factor. This very rare protein is known to promote the survival of neuronal populations that are all located either in the central nervous system or directly connected with it. The messenger RNA for brain-derived neurotrophic factor was found predominantly in the central nervous system, and the sequence of the protein indicates that it is structurally related to nerve growth factor. These results establish that these two neurotrophic factors are related both functionally and structurally.     

Shiverer peripheral myelin contains P2

Myelin-deficient mutant mice, such as shiverer, can provide information about the normal mechanisms involved in myelination. The shiverer mouse carries a recessive, autosomal mutation resulting in an extreme deficiency in central myelin, and the small amount of myelin present is poorly compacted; the peripheral myelin, however, appears essentially normal. As the amount of myelin basic protein (P1) in both central and peripheral nervous system myelin is extremely low in shiverer, it is possible that P1 is essential for the normal formation and compaction of central myelin, but not of peripheral myelin. Some other protein would then be responsible for the formation of compact peripheral myelin in shiverer. Peripheral myelin contains another basic protein, designated P2, which could be a possible candidate for this role. Kirschner and Ganser, however, using SDS-polyacrylamide gel electrophoresis, reported that P2, as well as P1, is absent from shiverer sciatic nerve. This is an important observation if correct, because it not only excludes the possibility that P2 is required for compaction but also makes it less likely that the deficiency in P1 is the primary defect in shiverer. As P2 in rat and mouse has frequently been confused with another small basic protein (related to P1) in SDS-polyacrylamide gels, it seemed worthwhile to reassess this aspect of the Kirschner and Ganser observations. Immunohistochemistry and immunoblotting have been used here to show unambiguously that P2 is present in shiverer peripheral myelin.