Development of "normal" dermatomes and somatotopic maps by "abnormal" populations of cutaneous neurons

During development, motor and sensory axons grow to peripheral targets with remarkable precision. Whereas much has been learned about the development of motoneuron connectivity, less is known about the regulation of cutaneous innervation. In adults, dorsal root ganglia (DRG) innervate characteristic skin regions, termed dermatomes, and their axons project somatotopically in the dorsal horn. Here, we have investigated whether cutaneous neurons are selectively matched with specific skin regions, and whether peripheral target skin influences the central connections of cutaneous neurons. To address these questions, we shifted limb buds rostrally in chick embryos prior to axon outgrowth, causing DRGs to innervate novel skin regions, and mapped the resulting dermatomes and central projections. Following limb shifts, cutaneous innervation arose from more rostral and from fewer DRGs than normal, but the overall dermatome pattern was preserved. Thus, DRGs parcel out innervation of skin in a consistent manner, with no indication of matching between skin and DRGs. Similarly, cutaneous nerves established a "normal" somatotopic map in the dorsal horn, but in more rostral segments than usual. Thus, the peripheral target skin may influence the pattern of CNS projections, but does not direct cutaneous axons to specific populations of neurons in the dorsal horn.     

Three-Dimensional Distribution of Sensory Stimulation-Evoked Neuronal Activity of Spinal Dorsal Horn Neurons Analyzed by In Vivo Calcium Imaging

The spinal dorsal horn comprises heterogeneous populations of interneurons and projection neurons, which form neuronal circuits crucial for processing of primary sensory information. Although electrophysiological analyses have uncovered sensory stimulation-evoked neuronal activity of various spinal dorsal horn neurons, monitoring these activities from large ensembles of neurons is needed to obtain a comprehensive view of the spinal dorsal horn circuitry. In the present study, we established in vivo calcium imaging of multiple spinal dorsal horn neurons by using a two-photon microscope and extracted three-dimensional neuronal activity maps of these neurons in response to cutaneous sensory stimulation. For calcium imaging, a fluorescence resonance energy transfer (FRET)-based calcium indicator protein, Yellow Cameleon, which is insensitive to motion artifacts of living animals was introduced into spinal dorsal horn neurons by in utero electroporation. In vivo calcium imaging following pinch, brush, and heat stimulation suggests that laminar distribution of sensory stimulation-evoked neuronal activity in the spinal dorsal horn largely corresponds to that of primary afferent inputs. In addition, cutaneous pinch stimulation elicited activities of neurons in the spinal cord at least until 2 spinal segments away from the central projection field of primary sensory neurons responsible for the stimulated skin point. These results provide a clue to understand neuronal processing of sensory information in the spinal dorsal horn.     

PlexinA1 signaling directs the segregation of proprioceptive sensory axons in the developing spinal cord

As different classes of sensory neurons project into the CNS, their axons segregate and establish distinct trajectories and target zones. One striking instance of axonal segregation is the projection of sensory neurons into the spinal cord, where proprioceptive axons avoid the superficial dorsal horn-the target zone of many cutaneous afferent fibers. PlexinA1 is a proprioceptive sensory axon-specific receptor for sema6C and sema6D, which are expressed in a dynamic pattern in the dorsal horn. The loss of plexinA1 signaling causes the shafts of proprioceptive axons to invade the superficial dorsal horn, disrupting the organization of cutaneous afferents. This disruptive influence appears to involve the intermediary action of oligodendrocytes, which accompany displaced proprioceptive axon shafts into the dorsal horn. Our findings reveal a dedicated program of axonal shaft positioning in the mammalian CNS and establish a role for plexinA1-mediated axonal exclusion in organizing the projection pattern of spinal sensory afferents.     

Somatotopy of Digital Nerve Projections to the Dorsal Horn in the Monkey

The dorsal horn projection patterns of finger nerves were investigated in four Macaca mulatto monkeys. Proper digital branches of the median nerves, serving the radial aspect of a digit on each hand, were loaded with wheatgerm agglutinin—horseradish peroxidase complex (WGA:HRP). The distribution of the lectin—enzyme complex was mapped in the right and left dorsal horns.

The dorsal horn projections of the digital nerves were localized in segments C₆-C₈ in laminae I-VI, primarily in laminae I-IV. The wedge-shaped termination zones were somatotopically organized, in agreement with the projections of the digits in cats. The fingers are represented medially, as they are in the cat. This similarity suggests that there is a mediolateral gradient of dorsal horn organization similar to that of the cat, with distal skin represented medially and proximal skin represented laterally. The rostrocaudal trajectory of finger representation, with digit 1 most rostral and digit 5 most caudal, is also in agreement with the organization of hindlimb toe projections in the cat. There was a high degree of bilateral symmetry for homologous nerves, and little overlap of projections from nerves innervating adjacent fingers. The sample size was too small to permit us to assess interanimal variation. These results suggest a similar somatotopy of projections, and presumably of dorsal horn cell somatotopy, in monkey and cat.     

Parallel radiations in the primary clades of birds

Knowledge of avian phylogeny is prerequisite to understanding the circumstances and timing of the diversification of birds and the evolution of morphological, behavioral, and life-history traits. Recent molecular datasets have helped to elucidate the three most basal clades in the tree of living birds, but relationships among neoavian orders (the vast majority of birds) remain frustratingly vexing. Here, we examine intron 7 of the beta-fibrinogen gene in the most taxonomically inclusive survey of DNA sequences of nonpasserine bird families and orders to date. These data suggest that Neoaves consist of two sister clades with ecological parallelisms comparable to those found between marsupial and placental mammals. Some members of the putative respective clades have long been recognized as examples of convergent evolution, but it was not appreciated that they might be parts of diverse parallel radiations. In contrast, some traditional orders of birds are suggested by these data to be polyphyletic, with representative families in both radiations.     

Detection of cold pain, cold allodynia and cold hyperalgesia in freely behaving rats

In mammals, somatosensory input activates feedback and feed-forward inhibitory circuits within the spinal cord dorsal horn to modulate sensory processing and thereby affecting sensory perception by the brain. Conventionally, feedback and feed-forward inhibitory activity evoked by somatosensory input to the dorsal horn is believed to be driven by glutamate, the principle excitatory neurotransmitter in primary afferent fibers. Substance P (SP), the prototypic neuropeptide released from primary afferent fibers to the dorsal horn, is regarded as a pain substance in the mammalian somatosensory system due to its action on nociceptive projection neurons. Here we report that endogenous SP drives a novel form of feed-forward inhibitory activity in the dorsal horn. The SP-driven feed-forward inhibitory activity is long-lasting and has a temporal phase distinct from glutamate-driven feed-forward inhibitory activity. Compromising SP-driven feed-forward inhibitory activity results in behavioral sensitization. Our findings reveal a fundamental role of SP in recruiting inhibitory activity for sensory processing, which may have important therapeutic implications in treating pathological pain conditions using SP receptors as targets.     

Somatotopy of digital nerve projections to the dorsal horn in the monkey

The dorsal horn projection patterns of finger nerves were investigated in four Macaca mulatta monkeys. Proper digital branches of the median nerves, serving the radial aspect of a digit on each hand, were loaded with wheatgerm agglutinin-horseradish peroxidase complex (WGA:HRP). The distribution of the lectin-enzyme complex was mapped in the right and left dorsal horns. The dorsal horn projections of the digital nerves were localized in segments C6-C8 in laminae I-VI, primarily in laminae I-IV. The wedge-shaped termination zones were somatotopically organized, in agreement with the projections of the digits in cats. The fingers are represented medially, as they are in the cat. This similarity suggests that there is a mediolateral gradient of dorsal horn organization similar to that of the cat, with distal skin represented medially and proximal skin represented laterally. The rostrocaudal trajectory of finger representation, with digit 1 most rostral and digit 5 most caudal, is also in agreement with the organization of hindlimb toe projections in the cat. There was a high degree of bilateral symmetry for homologous nerves, and little overlap of projections from nerves innervating adjacent fingers. The sample size was too small to permit us to assess interanimal variation. These results suggest a similar somatotopy of projections, and presumably of dorsal horn cell somatotopy, in monkey and cat.     

电刺激大鼠脊神经皮支对远距离机械感受单位电活动的影响

实验采用分离神经细束的方法,观察逆行电刺激大鼠脊神经背侧皮支后,在相距较远的神经细束上记录到的Aδ和C类机械感受单位电活动的变化。刺激T9脊神经背侧皮支,在T12神经细束上记录到59.3%（16/27）的Aδ和71.2%(37/52）的C类单位在刺激后90～120s放电显著增加。刺激T8脊神经背侧皮支,在T12神经细束上记录到47.8%(11/23）的Aδ单位和36.6%(15/41）的C类单位在刺激后120～150s放电显著增加。大多数单位（18/23）的机械感受阈值在电刺激远距离脊神经背侧皮支后降低。结果表明,逆行电刺激外周感觉神经,可以使相距较远的Aδ和C类机械感受单位致敏,其传入放电增加。     

微透析测试刺激皮肤和肌肉神经引起的天门冬氨酸和谷氨酸在脊髓的 …

To investigate the possible mechanisms underlying the difference of NMDA and non-NMDA receptors in spinal nociception originating in skin and muscle, release of aspartate (Asp) and glutamate (Glu) in the spinal dorsal horn was detected by stimulation of cutaneous and muscular nerves in cats using microdialysis technique. Asp and Glu were increased respectively by (323 +/- 55)% and (169 +/- 16)% following stimulation of cutaneous nerve, but by (150 +/- 16)% and (218 +/- 42)% respectively following stimulation of muscular nerve. Asp increase was approximately three times higher than that of Glu following cutaneous nerve-stimulation (P < 0.01), while Glu increase was approximately twice as high as that of Asp following muscular nerve-stimulation (P < 0.05). It is likely that nociceptive cutaneous and muscular inputs preferentially elicite release of Asp and Glu respectively, resulting in a functional differentiation of NMDA and non-NMDA receptor in the mediation of different nociceptive information.     

Qualitative analysis of proteins rapidly transported in ventral horn motoneurons and bidirectionally from dorsal root ganglia

Two-dimensional electrophoresis has allowed a higher-resolution comparison of rapid transport in ventral horn motoneurons and bidirectionally in dorsal root sensory neurons. Dorsal root ganglia 8 and 9, or hemisected spinal cords, from frog were selectively exposed in vitro to 35S-methionine. Transported, labelled proteins that accumulated in 3 mm segments proximal to ligatures on dorsal roots and spinal nerves or sciatic nerves were subjected to two-dimensional gel electrophoresis. Comparisons were made of fluorographic patterns from dried gels. Sixty-five species of proteins were found to be rapidly transported in both bifurcations of dorsal root sensory neurons. No abundant species of protein was rapidly transported in dorsal roots that was not also found in spinal nerves. A comparison of proteins rapidly transported in the sciatic nerve from ventral horn motoneurons with those from dorsal root sensory neurons yielded 50 common species of polypeptides. At most four minor species were possibly transported only in ventral horn motoneurons. An overall comparison indicates that at least 45 species of proteins, including all of the more abundantly transported ones, were consistently common to both dorsal root bifuractions and to ventral horn motoneurons. This appears to be the case despite the very different functions carried out by motoneurons and sensory neurons.     

Avian brain evolution: new data from Palaeogene birds (Lower Eocene) from England

Investigation of how the avian brain evolved to its present state is informative for studies of the theropod–bird transition, and as a parallel to mammalian brain evolution. Neurological anatomy in fossil bird species can be inferred from endocranial casts, but such endocasts are rare. Here, we use computed tomographic analysis to determine the state of brain anatomy in two marine birds from the Lower Eocene London Clay Formation of England. The brains of Odontopteryx (Odontopterygiformes) and Prophaethon (Pelecaniformes) are remarkably similar to those of extant seabirds, and probably possessed similar somatosensory and motor capabilities. Each virtual endocast exhibits a degree of telencephalic expansion comparable to living avian species. However, the eminentia sagittalis (wulst), a feature characteristic of all living birds, is poorly developed. Our findings support the conclusion that much of the telencephalic expansion of modern birds was complete by the end of the Mesozoic, but that overall telencephalic volume has increased throughout the Cenozoic through dorsal expansion of the eminentia sagittalis. We suggest that improvements in cognition relating to telencephalic expansion may have provided neornithine avian clades with an advantage over archaic lineages at the Cretaceous–Tertiary boundary, explaining their survival and rapid diversification in the Cenozoic. © 2009 The Natural History Museum. Journal compilation © 2009 The Linnean Society of London, Zoological Journal of the Linnean Society, 2009, 155 , 198–219.     

Innervation of the dermatomes in the neck of the mouse

The dorsal rami of the cervical and thoracic spinal nerves were investigated using both the in situ cholinesterase staining technique and cholinesterase staining on serial sections of plastic-embedded embryos. In most cases only the dorsal rami of the 2nd to 5th cervical spinal nerve possess cutaneous branches. The area innervated by the cutaneous branch of the dorsal ramus of the 5th spinal nerve borders on an area innervated by the cutaneous branch of the dorsal ramus of the 1st thoracic spinal nerve. The dorsal rami of the cervical spinal nerves 6-8 show no cutaneous branches. Therefore the gap in the series of the dorsal cutaneous branches is due only to the middle part of the nerves of the brachial plexus, which range from the 5th cervical nerve to the 1st thoracic nerve.     

Immunohistochemical study of cutaneous nerves in the emu

The distribution and chemical content of cutaneous nerves in 3- to 13-day-old emu chicks (Dromaius novaehollandiae) were examined by using double-labelling immunohistochemistry. Seven different subpopulations of cutaneous nerves were identified based on their neurochemistry. No intraepidermal nerve fibres were found. However, axons were located within the dermis and were often associated with blood vessels, pennamotor muscles and feather follicles or innervated Herbst corpuscles. Both similarities and differences exist between subpopulations of cutaneous nerves in the emu and volant birds. As in volant birds, a subpopulation of cutaneous axons innervates the superficial skin layers and contains immunoreactivity to both substance P and calcitonin gene-related peptide (CGRP). This suggests that the neuropeptide content of these presumptive free nerve endings is conserved throughout the evolution of birds. In contrast, Herbst corpuscles in the emu are innervated by axons that contain immunoreactivity for CGRP or neuropeptide Y (NPY) but that lack the calbindin D-28k immunoreactivity found in fibres innervating Herbst corpuscles of volant birds. Herbst corpuscles therefore may have a different chemical content in a flightless species from that in volant birds.This work was supported by an Australian Postgraduate Award (Industry; CO9942100) and the Flinders Institute for Health and Medical Research.     

Inter‐annual and body topographic consistency in the plumage bacterial load of Great Tits

ABSTRACT Plumage bacteria may play an important role in shaping the life histories of birds. However, to design suitable experiments to examine causal relationships between plumage bacteria and the fitness of host birds, natural variation in plumage bacterial communities needs to be better understood. We examined within‐individual consistency of plumage bacterial contamination in Great Tits (Parus major), comparing different body regions (ventral vs. dorsal) and comparing contamination between years. Numbers of free‐living and attached bacteria and the species richness of feather‐degrading bacterial assemblages were studied using flow cytometry and ribosomal intergenic spacer analysis (RISA). Numbers of both types of bacteria were higher on dorsal than on ventral feathers. Numbers of free‐living, but not attached, bacteria on the two body regions were highly positively correlated. There was also a strong within‐individual correlation between numbers of attached bacteria during the same breeding stages in different years. These results suggest that, despite variation in absolute levels of feather bacterial loads between years and different body regions, sampling individual birds can provide reliable estimates of relative levels of bacterial contamination, as long as sampling time and body region are carefully standardized.     

Spinal cord sensory systems after neonatal capsaicin

Animals with a severe reduction in the number of afferent C-fibres as a consequence of neonatal administration of capsaicin, exhibit a number of neurological and behavioral deficits including increased nociceptive thresholds, altered somato-visceral and viscero-visceral reflexes, depressed cardiovascular and respiratory reflexes and changes in the organisation of spinal cord sensory systems. The reduction in the number of C-fibres produced by neonatal capsaicin does not cause a decrease of similar magnitude in the number of dorsal horn cells driven by the surviving C-fibres. Twenty-two per cent of dorsal horn neurones in capsaicin treated animals respond to electrical stimulation of the surviving afferent C-fibres: a reduction of only 50% from control values. Inhibitory controls on afferent C-fibre evoked responses of dorsal horn neurones are weaker in capsaicin treated rate than in control animals. The cutaneous receptive fields of some dorsal horn neurones can increase in size following stimulation of afferent C-fibres. Tonic descending inhibition on C-fibre evoked responses of dorsal horn neurones is reduced in capsaicin treated rats: fewer neurones show tonic descending inhibition in these animals and those that do are subjected to less powerful inhibitions than similar neurones from control animals. However, some central inhibitory mechanism are unchanged after neonatal capsaicin treatment, specially those that do not involve afferent C-fibres. We suggest that the nervous system develops central inhibition in response to and directed towards the excitations mediated by its afferent drives. Therefore reduced central inhibition in response to a decreased number of afferent C-fibres can compensate for the lost capacity in the signalling of peripheral noxious events.     

Galanin-immunoreactive nerves in the female rat paracervical ganglion and uterine cervix: distribution and reaction to capsaicin

Summary The presence and distribution of galanin-immunoreactivity was examined in the uterine cervix and paracervical autonomic ganglia of the female rat. Some animals were treated with capsaicin to determine if galanin-immunoreactivity was present in small-diameter primary afferent nerves. Other animals were treated with the noradrenergic neurotoxin 6-hydroxydopamine to ascertain if galanin-immunoreactivity was present in sympathetic noradrenergic nerves. Galanin-immunoreactive nerve fibers were sparse in the cervical myometrium and vasculature, but numerous in the paracervical ganglion where they appeared to innervate principal neurons. Immunoreactivity was also present in dorsal root ganglia, dorsal horn of spinal cord, and inferior mesenteric ganglia. Capsaicin treatment resulted in a marked reduction of galanin-immunoreactivity in the spinal cord dorsal horn, but not in the dorsal root ganglia, paracervical ganglia, or cervix (although there was a substantial reduction of substance P-, neurokinin A-, and calcitonin gene-related peptide-immunoreactivity in the dorsal horn, dorsal root ganglia, and uterine cervix). 6-Hydroxydopamine treatment did not cause any appreciable change in the galanin-immunoreactivity in any tissues. We conclude that galanin-like immunoreactivity is expressed in nerve fibers innervating the paracervical ganglia and uterine cervix of the female rat. This immunoreactivity is probably present in afferent nerves and could play a role in neuroendocrine reflexes and in reproductive function.     

On mechanisms of depression in pathways of presynaptic inhibition

We investigated inhibition of the N₁-component of the spinal cord dorsal potential (CDP) evoked by experimental stimulation of the n. peroneus in spinal cats. Stimulation was carried out following two conditioning stimuli administered at different time intervals to the same or different cutaneous nerves. The interval between the last conditioning stimulus and the experimental one remained constant (20 msec). It is demonstrated that there is no dependence between weakening of inhibitory action of the second conditioning stimulus and inhibition of the dorsal horn interneurons excited by it that generate the N₁-component of the CDP. It is hypothesized that mechanisms which act on the principle of negative feedback are present in the vincinity of the synaptic junctions of cutaneous afferent fibers with neurons of the substantia gelationsa, and that these mechanisms restrict the development of presynaptic inhibition during inflow of a series of afferent impulses into the cord.Dnepropetrovsk State University. Translated from Neirofiziologia, Vol. 1, No. 3, pp. 253–261, November–December, 1969.     

Organization of motoneurons innervating the axial musculature of the brown caiman (Caiman crocodilus fuscus)

The primary divisions of the spinal nerve in the brown caiman characteristically show the following features: (1) the medial ramus was lies in the thoraco-lumbar and caudal regions, and (2) the first cervical and hypoglossal nerves form a single nerve complex from which the ventral and dorsal rami extend. Intramuscular injections of horseradish peroxidase (HRP) established the positions of motoneurons whose axons followed the primary rami. In the ventral horn of the thoracic and caudal spinal cord, the motoneurons of the medial ramus lie ventrally. These motoneurons lie between the epaxial and hypaxial motoneurons. At the spinomedullary junction, the pools of motoneurons innervating the infrahyoid, lingual, and dorsal muscles have a somatotopic organization similar to that observed in the thoraco-lumbar and caudal regions. Thus clear somatotopic organization of the motoneurons that innervate the axial musculature exists at all spinal levels. © 1994 Wiley-Liss, Inc.     

Functional anatomy of the canine mediastinal cardiac nerves located at the base of the heart

The major canine cardiopulmonary nerves which arise from the middle cervical and stellate ganglia and the vagi course toward the heart in the dorsal mediastinum where they form, at the base of the heart dorsal to the pulmonary artery and aorta, the dorsal mediastinal cardiac nerves. In addition, the left caudal pole and interganglionic nerves project onto the left lateral side of the heart as the left lateral cardiac nerve. These nerves contain afferent and (or) efferent axons which, upon stimulation, modify specific cardiac regions and (or) systemic pressure. In addition, with the exception of the left lateral cardiac nerve, stimulation of each of these nerves produces compound action potentials in the cranial ends of the majority of the major cardiopulmonary nerves demonstrating that axons in each dorsal mediastinal cardiac nerve interconnect with axons in the majority of the cardiopulmonary nerves. Axons in the left lateral cardiac nerve connect primarily with axons in the left caudal pole and left interganglionic nerves. The dorsal mediastinal nerves project distally onto the heart as coronary nerves accompanying the right or left coronary arteries. These innervated the ventricular myocardium which is supplied by their respective vessels. The left lateral cardiac nerve projects directly onto the lateral epicardium of the left ventricle. The dorsal mediastinal and left lateral cardiac nerves are the major sympathetic cardiac nerves. Thus, the cardiac nerves located in the mediastinum at the base of the heart are not simple extensions of cardiopulmonary nerves, but rather have a unique anatomy and function of their own.