Ontogeny of a Simple Locomotor System: Role of the Periphery in the Development of Central Nervous Circuitry

The development of locomotor systems in the lobster Homarusamericanus is described. The tail—flip escape responseis fully developed when the larvae hatch, and occurs withoutthe participation of giant fibers. The abdominal swimmeretsare undifferentiated at hatching, but are fully developed twoto three weeks later when the animals molt to the fourth larvalstage. Forward locomotion in the pelagic larvae is achievedusing thoracic swimming appendages until the fourth larval stage,when these degenerate and the swimmerets assume the locomotorrole. The hypothesis that peripheral structures specify the centralnervous connections of motoneurons during ontogeny was testedin the swimmeret system. Presumptive swimmeret appendages, includingprospective muscle and sense organs, were extirpated prior totheir differentiation in newly hatched larvae. The correspondingswimmeret motoneurons nevertheless grew and formed normal centralconnections, as evidenced by the appearance of normal patternsof rhythmic locomotor discharge and normal reflexes at the usualtime. Moreover, swimmeret motoneurons retained normal patternsof motor output even when the regeneration of their target appendageswas prevented for as long as two months. Therefore, the formationof normal motor output patterns during ontogeny is not dependentupon feedback from differentiated target muscle nor from senseorgans which normally monitor the results of the motor activity.     

Neural Correlates of Central Inhibition during Physical Fatigue

Central inhibition plays a pivotal role in determining physical performance during physical fatigue. Classical conditioning of central inhibition is believed to be associated with the pathophysiology of chronic fatigue. We tried to determine whether classical conditioning of central inhibition can really occur and to clarify the neural mechanisms of central inhibition related to classical conditioning during physical fatigue using magnetoencephalography (MEG). Eight right-handed volunteers participated in this study. We used metronome sounds as conditioned stimuli and maximum handgrip trials as unconditioned stimuli to cause central inhibition. Participants underwent MEG recording during imagery of maximum grips of the right hand guided by metronome sounds for 10 min. Thereafter, fatigue-inducing maximum handgrip trials were performed for 10 min; the metronome sounds were started 5 min after the beginning of the handgrip trials. The next day, neural activities during imagery of maximum grips of the right hand guided by metronome sounds were measured for 10 min. Levels of fatigue sensation and sympathetic nerve activity on the second day were significantly higher relative to those of the first day. Equivalent current dipoles (ECDs) in the posterior cingulated cortex (PCC), with latencies of approximately 460 ms, were observed in all the participants on the second day, although ECDs were not identified in any of the participants on the first day. We demonstrated that classical conditioning of central inhibition can occur and that the PCC is involved in the neural substrates of central inhibition related to classical conditioning during physical fatigue.     

Psychophysical Evaluation of a Sanshool Derivative (Alkylamide) and the Elucidation of Mechanisms Subserving Tingle

Previous studies investigated the neural and molecular underpinnings of the tingle sensation evoked by sanshool and other natural or synthetic alkylamides. Currently, we sought to characterize the psychophysical properties associated with administration of these compounds. Like other chemesthetic stimuli, the synthetic tingle analog isobutylalkylamide (IBA) evoked a sensation that was temporally dynamic. Repeated IBA application at short (30 sec) interstimulus intervals (ISI) resulted in a tingle sensation that increased across trials. Application at longer ISIs (∼30 min) resulted in a sensation of decreased intensity consistent with self-desensitization. Prior treatment with the TRPV1 or TRPA1 agonists, capsaicin and mustard oil did not cross-desensitize the tingle sensation evoked by IBA suggesting that neither TRPV1 nor TRPA1 participate in the transduction mechanism sub-serving tingle. When evaluated over 30-min time period, lingual IBA evoked a sensation that was described initially as tingling and pungent but after approximately 15 min, as a cooling sensation. Further, we found that the sensation evoked by lingual IBA was potentiated by simultaneous application of cold (0°C) and cool (21°C) thermal stimuli but was unaffected by warm (33°C) and hot (41°C) temperatures. Finally, to test the hypothesis that the tingling sensation is subserved by the activation of mechanosensitve fibers, we evaluated lingual tactile thresholds in the presence and absence of lingual IBA. The presence of IBA significantly raised lingual tactile thresholds, whereas capsaicin did not, identifying a role for mechanosensitive fibers in conveying the tingle sensation evoked by sanshool-like compounds. Collectively, these results show that lingual alkylamide evokes a complex sensation that is temporally dynamic and consistent with in vitro and in vivo experiments suggesting these compounds activate mechanosensitve neurons via blockade of KCNK two-pore potassium channels to induce the novel tingling sensation.     

Maasai Identity on the Periphery

This article examines ethnic identity among the Maasai-related II Chamus of Baringo District, Kenya. Through an analysis of land policies, it shows how colonialism forged identities and boundaries that had scarcely existed in the 19th century. These are now fiercely defended on the basis of "tradition." By examining how identities are shaped by power, the article contributes to the understanding of the political nature of ethnicity and the "ethnic" conflict in Kenya.     

Notes on a Lithic Micro-Tool Industry From The Plains Periphery

Abstract

Excavations at the Kimberlin Site (23CR301) during the period of 1969-1970 provided evidence of a unique micro-tool assemblage. Because of the unusual nature of this flake tool kit a brief, preliminary consideration of its nature and diversity is presented.     

Learning Contrast-Invariant Cancellation of Redundant Signals in Neural Systems

Cancellation of redundant information is a highly desirable feature of sensory systems, since it would potentially lead to a more efficient detection of novel information. However, biologically plausible mechanisms responsible for such selective cancellation, and especially those robust to realistic variations in the intensity of the redundant signals, are mostly unknown. In this work, we study, via in vivo experimental recordings and computational models, the behavior of a cerebellar-like circuit in the weakly electric fish which is known to perform cancellation of redundant stimuli. We experimentally observe contrast invariance in the cancellation of spatially and temporally redundant stimuli in such a system. Our model, which incorporates heterogeneously-delayed feedback, bursting dynamics and burst-induced STDP, is in agreement with our in vivo observations. In addition, the model gives insight on the activity of granule cells and parallel fibers involved in the feedback pathway, and provides a strong prediction on the parallel fiber potentiation time scale. Finally, our model predicts the existence of an optimal learning contrast around 15% contrast levels, which are commonly experienced by interacting fish.     

Neural Regeneration: Lessons from Regenerating and Non-regenerating Systems

One only needs to see a salamander regrowing a lost limb to become fascinated by regeneration. However, the lack of robust axonal regeneration models for which good cellular and molecular tools exist has hampered progress in the field. Nevertheless, the nervous system has been revealed to be an excellent model to investigate regeneration. There are conspicuous differences in neuroregeneration capacity between amphibia and warm-blooded animals, as well as between the central and the peripheral nervous systems in mammals. Exploration of such discrepancies led to significant discoveries on the basic tenets of neuroregeneration in the last two decades, identifying several positive and negative regulators of axonal regeneration. Implications of these findings to the comprehension of mammalian regeneration and to the development of spinal cord injury therapies are also addressed.     

Pulse Frequency Modulation in Neural Systems: A Random Model

A model is proposed of the pulse frequency modulation process in those neural systems where the neuron discharge is random. The model is characterized by one property, namely input-invariance of the output random process after a time transformation, which, on the one hand, greatly simplifies its analytical treatment, and on the other hand, gives a tool to determine experimentally whether the model describes the external behavior of a given neural system. The main dynamical properties of the model are studied, and the relevance of the results to information transmission by neural systems is discussed.     

Self-Organizing Task Modules and Explicit Coordinate Systems in a Neural Network Model for 3-D Saccades

The goal of this study was to train an artificial neural network to generate accurate saccades in Listing's plane and then determine how the hidden units performed the visuomotor transformation. A three-layer neural network was successfully trained, using back-prop, to take in oculocentric retinal error vectors and three-dimensional eye orientation and to generate the correct head-centric motor error vector within Listing's plane. Analysis of the hidden layer of trained networks showed that explicit representations of desired target direction and eye orientation were not employed. Instead, the hidden-layer units consistently divided themselves into four parallel modules: a dominant "vector-propagation" class (approximately 50% of units) with similar visual and motor tuning but negligible position sensitivity and three classes with specific spatial relations between position, visual, and motor tuning. Surprisingly, the vector-propagation units, and only these, formed a highly precise and consistent orthogonal coordinate system aligned with Listing's plane. Selective "lesions" confirmed that the vector-propagation module provided the main drive for saccade magnitude and direction, whereas a balance between activity in the other modules was required for the correct eye-position modulation. Thus, contrary to popular expectation, error-driven learning in itself was sufficient to produce a "neural" algorithm with discrete functional modules and explicit coordinate systems, much like those observed in the real saccade generator.     

Nonsteroidal Anti-Inflammatory Drugs Increase Tumor Necrosis Factor Production in the Periphery but Not in the Central Nervous System in Mice and Rats

Abstract: Nonsteroidal anti-inflammatory drugs (NSAIDs), which inhibit prostaglandin (PG) synthesis, augment production of tumor necrosis factor (TNF) in most experimental models. We investigated the effect of two NSAIDs, indomethacin and ibuprofen, on the production of TNF in the CNS induced by intracerebroventricular injection of lipopolysaccharide (LPS). Indomethacin and ibuprofen, administered intraperitoneally, augmented (three- to ninefold) the levels of TNF in serum and peripheral organs of mice injected intraperitoneally with LPS and in rats with adjuvant arthritis (up to a sevenfold increase). However, NSAIDs (intraperitoneally or intracerebroventricularly) did not increase brain TNF production induced by intravenous LPS. In fact, indomethacin decreased (1.4–1.8-fold) TNF levels in the spinal cord of rats with experimental autoimmune encephalomyelitis and in the cortex of rats with focal cerebral ischemia. Systemic administration of iloprost inhibited serum TNF levels after intraperitoneal LPS, whereas intracerebroventricular injection of iloprost or PGE₂ did not inhibit brain TNF induced by intracerebroventricular LPS. Both peripheral and central TNF productions were inhibited by cyclic AMP level-elevating agents or dexamethasone. Thus, a PG-driven negative feedback controls TNF production in the periphery but not in the CNS.     

Slow Breathing and Hypoxic Challenge: Cardiorespiratory Consequences and Their Central Neural Substrates

Controlled slow breathing (at 6/min, a rate frequently adopted during yoga practice) can benefit cardiovascular function, including responses to hypoxia. We tested the neural substrates of cardiorespiratory control in humans during volitional controlled breathing and hypoxic challenge using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers were scanned during paced (slow and normal rate) breathing and during spontaneous breathing of normoxic and hypoxic (13% inspired O₂) air. Cardiovascular and respiratory measures were acquired concurrently, including beat-to-beat blood pressure from a subset of participants (N = 7). Slow breathing was associated with increased tidal ventilatory volume. Induced hypoxia raised heart rate and suppressed heart rate variability. Within the brain, slow breathing activated dorsal pons, periaqueductal grey matter, cerebellum, hypothalamus, thalamus and lateral and anterior insular cortices. Blocks of hypoxia activated mid pons, bilateral amygdalae, anterior insular and occipitotemporal cortices. Interaction between slow breathing and hypoxia was expressed in ventral striatal and frontal polar activity. Across conditions, within brainstem, dorsal medullary and pontine activity correlated with tidal volume and inversely with heart rate. Activity in rostroventral medulla correlated with beat-to-beat blood pressure and heart rate variability. Widespread insula and striatal activity tracked decreases in heart rate, while subregions of insular cortex correlated with momentary increases in tidal volume. Our findings define slow breathing effects on central and cardiovascular responses to hypoxic challenge. They highlight the recruitment of discrete brainstem nuclei to cardiorespiratory control, and the engagement of corticostriatal circuitry in support of physiological responses that accompany breathing regulation during hypoxic challenge.     

Midline Signalling Systems Direct the Formation of a Neural Map by Dendritic Targeting in the Drosophila Motor System

A fundamental strategy for organising connections in the nervous system is the formation of neural maps. Map formation has been most intensively studied in sensory systems where the central arrangement of axon terminals reflects the distribution of sensory neuron cell bodies in the periphery or the sensory modality. This straightforward link between anatomy and function has facilitated tremendous progress in identifying cellular and molecular mechanisms that underpin map development. Much less is known about the way in which networks that underlie locomotion are organised. We recently showed that in the Drosophila embryo, dendrites of motorneurons form a neural map, being arranged topographically in the antero-posterior axis to represent the distribution of their target muscles in the periphery. However, the way in which a dendritic myotopic map forms has not been resolved and whether postsynaptic dendrites are involved in establishing sets of connections has been relatively little explored. In this study, we show that motorneurons also form a myotopic map in a second neuropile axis, with respect to the ventral midline, and they achieve this by targeting their dendrites to distinct medio-lateral territories. We demonstrate that this map is “hard-wired”; that is, it forms in the absence of excitatory synaptic inputs or when presynaptic terminals have been displaced. We show that the midline signalling systems Slit/Robo and Netrin/Frazzled are the main molecular mechanisms that underlie dendritic targeting with respect to the midline. Robo and Frazzled are required cell-autonomously in motorneurons and the balance of their opposite actions determines the dendritic target territory. A quantitative analysis shows that dendritic morphology emerges as guidance cue receptors determine the distribution of the available dendrites, whose total length and branching frequency are specified by other cell intrinsic programmes. Our results suggest that the formation of dendritic myotopic maps in response to midline guidance cues may be a conserved strategy for organising connections in motor systems. We further propose that sets of connections may be specified, at least to a degree, by global patterning systems that deliver pre- and postsynaptic partner terminals to common “meeting regions.”     

Concentrating Engines and the Kidney: II. Multisolute Central Core Systems

The analysis of the central core model of the renal medulla is extended to multisolute systems. It is shown that total solute concentration obeys the same differential equations for core and ascending limb as in a single solute system. Equations are derived for the concentration of individual solutes. Application of these equations to a two solute system shows that a central core system can concentrate with all transport being down a concentration gradient. This analysis applied to the renal medulla shows that mixing of urea from the collecting duct (CD) and salt from the loop of Henle in the central core of the inner medulla contributes to the concentration of urine during antidiuresis. It also sets criteria for completely passive function of the loop in the inner medulla, but whether these are satisfied cannot be determined from present experimental data.     

Silver Staining of Insect Central Nervous Systems by the Bodian Protargol Method

Improved fixation of ganglia of the central nervous system of Periplaneta americana and Schistocerca gregaria for silver staining by Power's (1943) modification of the Bodian protargol method is given by alcoholic Bouin aged for at least 40 days at 60° C. During impregnation of sections, increased copper and decreased pH give paler staining, more selective for nerve fibres. Prolonging impregnation from 24 to 48 hours weakens the stain and decreases selectivity. The intensity of the stain depends chiefly upon the amount of unreduced (developable) silver combined with the tissues; selectivity is determined mainly by the number and distribution of the reduced silver particles (‘nuclei’). In development, increased sodium sulphite gives more differentiation, increased hydroquinone gives less. Optimum developer composition depends upon impregnation, and thick sections need more differentiation than thinner ones. Within limits, change in one of the factors that control staining can be balanced by changes in others, but by suitable adjustment of the conditions the result can be varied from almost total staining of nerve fibres, for general neuroanatomy, to highly selective staining for tracing individual fibres.