GAP-43 expression in the medulla of macaque monkeys: changes during postnatal development and the effects of early median nerve repair.

Abstract: The extent of the cortical somatotopic map and its relationship to phantom phenomena was tested in five subjects with congenital absence of an upper limb, four traumatic amputees with phantom limb pain and five healthy controls. Cortical maps of the first and fifth digit of the intact hand, the lower lip and the first toe (bilaterally) were obtained using neuroelectric source imaging. The subjects with congenital upper limb atrophy showed symmetric positions of the left and right side of the lower lip and the first toe, whereas the traumatic amputees with pain showed a significant shift (about 2.4 cm) of the cortical representation of the lower lip towards the hand region contralateral to the amputation side but no shift for the toe representation. In healthy controls, no significant hemispheric differences between the cortical representation of the digits, lower lip or first toe were found. Phantom phenomena were absent in the congenital but extensive in the traumatic amputees. These data confirm the assumption that congenital absence of a limb does not lead to cortical reorganization or phantom limbs whereas traumatic amputations that are accompanied by phantom limb pain show shifts of the cortical areas adjacent to the amputation zone towards the representation of the deafferented body part.

Abstract: Transection of a sensory nerve in adults results in profound abnormalities in sensory perception, even if the severed nerve is surgically repaired to facilitate accurate nerve regeneration. In marked contrast, fewer perceptual errors follow nerve transection and surgical repair in children. The basis for this superior recovery in children was unknown. Here we show that there is little or no topographic order in the median nerve to the hand after median nerve section and surgical repair in immature macaque monkeys. Remarkably, however, in the same animals the representation of the reinnervated hand in primary somatosensory cortex area (area 3b) is quite orderly. This indicates that there are mechanisms in the developing brain that can create cortical topography, despite disordered sensory inputs. Presumably the superior recovery of perceptual abilities after peripheral nerve transection in children depends on this restoration of somatotopy in the central sensory maps.

Abstract: Neurotrophic factors play an important modulatory role in axonal sprouting during nerve regeneration involving the proliferation of hematogenous and Schwann cells in damaged tissue. We have exposed lesioned sciatic nerves to a collagen prosthesis with covalently bonded small cell adhesive peptides Arg-Gly-Asp-Ser (RGDS), Lys-Arg-Asp-Ser (KRDS), and Gly-His-Lys (GHK) to study local production of growth factors and cytokines in the regenerating tissues. Western/enzyme-linked immunosorbent assay (ELISA) studies were performed after 10 days of regeneration, when the tubular prosthesis is filled with fibrous matrix infiltrated by hematogenous cells and proliferating Schwann cells with growth factors produced locally. Regeneration was also analyzed by morphometrical methods after 30 days. The quantification of growth factors and proteins by ELISA revealed that there was an enhanced expression of the neurotrophic factors nerve growth factor (NGF) and neurotrophins (NT-3 and NT-4) in the regenerating tissues. This was further established by Western blot to qualitatively analyze the presence of the antigens in the regenerating tissues. Schwann cells were localized in the regenerating tissues using antibodies against S-100 protein. Other growth factors including growth-associated protein 43 (GAP-43), apolipoprotein E (Apo E), and pro-inflammatory cytokine like interleukin-1alpha (IL-1alpha) expression in the peptide groups were evaluated by ELISA and confirmed by Western blotting. Cell adhesive integrins in the proliferating cells were localized using integrin-alpha V. The combined results suggest that the early phase of regeneration of peripheral nerves in the presence of peptide-incorporated collagen tubes results in the enhanced production of trophic factors by the recruited hematogenous cells and Schwann cells, which in turn help in the secretion of certain vital trophic and tropic factors essential for early regeneration. Furthermore, hematogenous cells recruited within the first 10 days of regeneration help in the production of inflammatory mediators like interleukins that in turn stimulate Schwann cells to produce NGF for axonal growth.

Abstract: Two basic features of our brains seem almost incompatible with each other One feature is the processing of information in a predictable and reliable manner In order to do this, one would suppose that the machinery of the brain, the local circuits and processing pathways, would be morphologically and functionally stable, at least in adults Yet, the second feature-the ability to adjust to changes in the external environment-is critical for learning and for recovery from brain injury How can circuits change and yet allow us to respond in a reliable way? Many investigators resolved this quandary by assuming that although most circuits in the brain

Abstract: Neuronal growth-associated protein 43 (GAP43) has crucial roles in the nervous system, and during development, regeneration after injury, and learning and memory. GAP43 is expressed in mouse skeletal muscle fibers and satellite cells, with suggested its involvement in intracellular Ca2+ handling. However, the physiological role of GAP43 in muscle remains unknown. Using a GAP43-knockout (GAP43-/-) mouse, we have defined the role of GAP43 in skeletal muscle. GAP43-/- mice showed low survival beyond weaning, reduced adult body weight, decreased muscle strength, and changed myofiber ultrastructure, with no significant differences in the expression of markers of satellite cell and myotube progression through the myogenic program. Thus GAP43 expression is involved in timing of muscle maturation in-vivo. Intracellular Ca2+ measurements in-vitro in myotubes revealed GAP43 involvement in Ca2+ handling. In the absence of GAP43 expression, the spontaneous Ca2+ variations had greater amplitudes and higher frequency. In GAP43-/- myotubes, also the intracellular Ca2+ variations induced by the activation of dihydropyridine and ryanodine Ca2+ channels, resulted modified. These evidences suggested dysregulation of Ca2+ homeostasis. The emerging hypothesis indicates that GAP43 interacts with calmodulin to indirectly modulate the activities of dihydropyridine and ryanodine Ca2+ channels. This thus influences intracellular Ca2+ dynamics and its related intracellular patterns, from functional excitation-contraction coupling, to cell metabolism, and gene expression.

Abstract: Each edition of this classic reference has proved to be a benchmark in the developing field of cognitive neuroscience. The fourth edition of The Cognitive Neurosciences continues to chart new directions in the study of the biologic underpinnings of complex cognition -- the relationship between the structural and physiological mechanisms of the nervous system and the psychological reality of the mind. The material in this edition is entirely new, with all chapters written specifically for it. Since the publication of the third edition, the field of cognitive neuroscience has made rapid and dramatic advances; fundamental stances are changing and new ideas are emerging. This edition reflects the vibrancy of the field, with research in development and evolution that finds a dynamic growth pattern becoming specific and fixed, and research in plasticity that sees the neuronal systems always changing; exciting new empirical evidence on attention that also verifies many central tenets of longstanding theories; work that shows the boundaries of the motor system pushed further into cognition; memory research that, paradoxically, provides insight into how humans imagine future events; pioneering theoretical and methodological work in vision; new findings on how genes and experience shape the language faculty; new ideas about how the emotional brain develops and operates; and research on consciousness that ranges from a novel mechanism for how the brain generates the baseline activity necessary to sustain conscious experience to a bold theoretical attempt to make the problem of qualia more tractable.

Abstract: Endogenous cytochrome oxidase activity within the mitochondria of neurons and neuropil was demonstrated histochemically under normal and experimental conditions. Since enzymatic changes were noted with chronic neuronal inactivity in the auditory system (Wong-Riley et al), the present study sought to examine functionally induced enzymatic changes in the visual system of kittens. Eight kittens were used experimentally: 5 had monocular lid suture for varying periods of time; one had binocular lid suture followed by monocular suture followed by binocular opening; two had monocular enucleation. All initial procedures were performed before eye opening. Materials from other normal kittens and cats were also used as controls. At the end of the experiments, the animals were perfused with aldehyde solutions and frozen sections of the brains were incubated for cytochrome oxidase activity (a detailed protocol was outlined). The results indicated that the deprivation caused by monocular suture produced a decrease in the cytochrome oxidase staining of the binocular segment of the deprived geniculate laminae. Enucleation yielded a greater decrease in the cytochrome oxidase activity in the affected geniculate laminae. However, the staining in the 'normal' lamina extended across the interlaminar border to include a row of surviving large cells in the 'denervated' lamina. The staining of the monocular segment appeared not to be affected by lid suture, but was decreased by enucleation. At the cortical level, lamina IV in area 17 of normal cats was stained darkly as a continuous band. Following lid suture, this pattern was replaced in part by alternating columns of light and dark staining, suggestive of ocular dominance columns. Thus, a decrease in neuronal activity due to reduced visual stimulation or destruction of the primary afferent nerves led to a significant decrease in the level of oxidative enzyme activity one to several synapses away.

Abstract: 1 Introduction.- 2 Peripheral Nerves and Sensory Receptors.- 3 Dorsal Root Ganglion Cells and Their Processes.- 4 Structure of the Dorsal Horn.- 5 Functional Organization of Dorsal Horn Interneurons.- 6 Ascending Sensory Pathways in the Cord White Matter.- 7 Sensory Pathways in the Dorsal Funiculus.- 8 Sensory Pathways in the Dorsal Lateral Funiculus.- 9 Sensory Pathways in the Ventral Quadrant.- 10 The Sensory Channels.- References.

Abstract: This rev iew addresses questions about t he capacity of sensory and motor maps in the brains of adul t mammals to change as a resul t of alterations in the effectiveness of inputs, the availability of effectors, and d irect damage. The issue of the mutabil ity of maps in adults is important because sensory and motor representations occupy much of the brains of mammals, regardless of the complexity and extent of neocortex (e.g. Kaas 1988, Wall 1988, Maunsell & Newsome 1987); behavioral recovery occurs after damage to central representations (e.g. Bor nschlegl & Asanuma 1987, Diirsteler et a11987, Eidelberg & Stein 1974); and such changes may relate to improvements in sensory and motor skills with experience (e.g. Gibson 1953). Tn addition, features of reorganization that are apparent in sensory and motor maps may characterize less easily studied areas of the brain. Specific questions addr essed in this review are as follows: