Egbert A. J. F. Lakke

Type grouping in skeletal muscles after experimental reinnervation: another explanation

Type grouping signifies clustering of muscle fibres of the same metabolic type, and is a frequent finding in reinnervated muscles. To elucidate the mechanism behind it, the rat sciatic nerve was either autografted or grafted with hollow synthetic nerve grafts. Twelve weeks later the number and fibre area of the type I and type II muscle fibres in the gastrocnemic and anterior tibial muscles were determined after ATP‐ase staining. The number and diameter of peroneal nerve fibres distal to the grafts were measured, and the number of Aα‐nerve fibres was derived. Nearly all nerve and muscle morphometrical parameters changed equally in both experimental groups. However, type grouping occurred frequently only after autografting, whereas the number of nerve fibres and the number of Aα‐nerve fibres increased in this group. Hence type grouping cannot be explained by increased intramuscular sprouting subsequent to a decrease in the number of innervating nerve fibres, as previously presumed. Regenerating axons branch along their course through the peripheral nerve. We propose that the probability of the occurrence of type grouping is related to the dispersion of sibling branches in the nerve. In the autograft, emerging branches are kept together by Schwann cell basal lamina scaffolds, in contrast to the hollow synthetic nerve grafts where the emerging branches become dispersed. Thus, in muscles reinnervated after autografting, the probability that nerve branches that arrive at a specific muscle territory are sibling branches is greater than after hollow tube grafting. Consequently, the probability that type grouping will occur is greater.

Electrophysiology and morphometry of the Aα- and Aβ-fiber populations in the normal and regenerating rat sciatic nerve

We studied electrophysiological and morphological properties of the Aa- and Ah-fibers in the regenerating sciatic nerve to establish whether these fiber types regenerate in numerical proportion and whether and how the electrophysiological properties of these fiber types are adjusted during regeneration. Compound action potentials were evoked from isolated sciatic nerves 12 weeks after autografting. Nerve fibers were gradually recruited either by increasing the stimulus voltage from subthreshold to supramaximal levels or by increasing the interval between two supramaximal stimuli to obtain the cumulative distribution of the extracellular firing thresholds and refractory periods, respectively. Thus, the mean conduction velocity (MCV), the maximal charge displaced during the compound action potential (Qmax), the mean firing threshold (V50), and the mean refractory period (t50) were determined. The number of myelinated nerve fibers and their fiber diameter frequency distributions were determined in the peroneal nerve. Mathematical modeling applied to fiber recruitment and diameter distributions allowed discrimination of the Aa- and Ah-fiber populations. In regenerating nerves, the number of Aa-fibers increased fourfold while the number of Ah-fibers did not change. In regenerating Aa- and Ah-fibers, the fiber diameter decreased and V50 and t50 increased. The regenerating Aa-fibers’ contribution to Qmax decreased considerably while that of the Ah-fibers remained the same. Correlation of the electrophysiological data to the morphological data provided indications that the ion channel composition of both the Aa- and Ah-fibers are altered during regeneration. This demonstrates that combining morphometric and electrophysiological analysis provides better insight in the changes that occur during regeneration.

The subthalamic nucleus. Part I: development, cytology, topography and connections.

This monograph (Part I of two volumes) on the subthalamic nucleus (STN) accentuates the gap between experimental animal and human information concerning subthalamic development, cytology, topography and connections. The light and electron microscopical cytology focuses on the open nucleus concept and the neuronal types present in the STN. The cytochemistry encompasses enzymes, NO, glial fibrillary acidic protein (GFAP), calcium binding proteins, and receptors (dopamine, cannabinoid, opioid, glutamate, gamma-aminobutyric acid (GABA), serotonin, cholinergic, and calcium channels). The ontogeny of the subthalamic cell cord is also reviewed. The topography concerns the rat, cat, baboon and human STN. The descriptions of the connections are also given from a historical point of view. Recent tracer studies on the rat nigro-subthalamic connection revealed contralateral projections. Part II of the two volumes (volume 199) on the subthalamic nucleus (STN) starts with a systemic model of the basal ganglia to evaluate the position of the STN in the direct, indirect and hyperdirect pathways. A summary of in vitro studies is given, describing STN spontaneous activity as well as responses to depolarizing and hyperpolarizing inputs and high-frequency stimulation. STN bursting activity and the underlying ionic mechanisms are investigated. Deep brain stimulation used for symptomatic treatment of Parkinsons disease is discussed in terms of the elements that are influenced and its hypothesized mechanisms. This part of the monograph explores the pedunculopontine-subthalamic connections and summarizes attempts to mimic neurotransmitter actions of the pedunculopontine nucleus in cell cultures and high-frequency stimulation on cultured dissociated rat subthalamic neurons. STN cell models--single- and multi-compartment models and system-level models are discussed in relation to subthalamic function and dysfunction. Parts I and II are compared.

Intrinsic properties of the developing motor cortex in the rat: in vitro axons from the medial somatomotor cortex grow faster than axons from the lateral somatomotor cortex

The axons that originate in the medial somatomotor cortex of the rat depart, during development, after those from the lateral somatomotor cortex, yet they arrive in the cervical spinal cord first. Either the medially originating axons elongate faster, or the laterally originating ones pause along the descent pathway. To investigate the presence of an intrinsic difference of the axonal elongation velocity between the lateral and medial somatomotor cortical areas, we cultured explants taken from these areas for 2 days, and measured the length of the outgrowth. After 2 days the explants were surrounded by a radiate corona of axons of which the longest measured 1.95 mm. A significant difference was detected between the medial and lateral somatomotor cortical areas in vitro. Axons originating from explants taken from the medial somatomotor cortical area are, after 2 days in culture, on average 0.16 mm longer than those from the lateral somatomotor cortical area. Though the observed difference is not large enough to allow for the overtaking observed in vivo, it does indicate that intrinsic differences exist within the developing rat somatomotor cortex. This in turn indicates that intrinsic cortical traits not only influence regionalization and targeting behavior of cortical projection neurons, but also their axonal elongation speed.

Retrograde labeling of retinal ganglion cells and brain neuronal subsets by [3H]-d-aspartate injection in the Syrian hamster hypothalamus

The circadian pacemaker in the suprachiasmatic nuclei (SCN) is entrained to the environmental light-dark cycle via a direct retinal projection to the hypothalamus. This projection is thought to use glutamate or aspartate as neurotransmitter. [3H]-D-Aspartate was microinjected in the SCN and adjacent hypothalamic nuclei of Syrian hamsters. This neuronal tracer is selectively taken up by terminals of neurons that use glutamate or aspartate as neurotransmitter and retrogradely transported to their perikarya. With autoradiography labeled cells were visualized in the retinal ganglion cell layer. Labeled cells were also found in a subset of brain nuclei known to project to the injection area. Labeled cells were detected in the bed nucleus of the stria terminalis, paraventricular nucleus of the thalamus, lateral septal nucleus, and medial amygdaloid nucleus. No labeled cells were observed in the medial septal nucleus, intergeniculate leaflet, and ventral lateral geniculate nucleus, which are also known to project to the SCN. Our results indicate that glutamatergic/aspartatergic retinal ganglion cells project to the SCN and adjacent medial hypothalamic nuclei. Moreover, the SCN may receive glutamatergic/aspartatergic input from the brain neuronal subsets that were retrogradely labeled with [3H]-D-aspartate.

Effect of nerve graft porosity on the refractory period of regenerating nerve fibers

OBJECT In the present study the authors consider the influence of the porosity of synthetic nerve grafts on peripheral nerve regeneration. METHODS Microporous (1-13 microm) and nonporous nerve grafts made of a copolymer of trimethylene carbonate and epsilon-caprolactone were tested in an animal model. Twelve weeks after surgery, nerve and muscle morphological and electrophysiological results of regenerated nerves that had grown through the synthetic nerve grafts were compared with autografted and untreated (control) sciatic nerves. Based on the observed changes in the number and diameter of the nerve fibers, the predicted values of the electrophysiological parameters were calculated. RESULTS The values of the morphometric parameters of the peroneal nerves and the gastrocnemius and anterior tibial muscles were similar if not equal in the rats receiving synthetic nerve grafts. The refractory periods, however, were shorter in porous compared with nonporous grafted nerves, and thus were closer to control values. CONCLUSIONS A shorter refractory period enables the axon to follow the firing frequency of the neuron more effectively and allows a more adequate target organ stimulation. Therefore, porous are preferred over nonporous nerve grafts.

Lumbar spinal cord explants from neonatal rat display age-related decrease of outgrowth in culture

Lumbar spinal cord explants, harvested from neonatal rat pups aged between postnatal day 0 (P0) and P7, were cultured for a period of 48 h in the chemically defined medium R(12) [17] (Romijn, H.J., van-Huijen, F., Wolters, P.S., Neurosci Biobehav Rev, 8 (1984) 301-334), embedded in a collagen matrix. The outgrowth into the surrounding matrix was quantified. Age-matched cortical explants were used as controls. Despite adaptations of the culture protocol, outgrowth remained variable. Statistical analysis demonstrated a clear relation between the age of the explant (at the time of explantation) and the number of neurites in the corona surrounding the explant. The number of outgrowing neurites decreased sharply with age. The average number of neurites per explant obeyed to the expression log(N)= -0.652 A+17 (N: the number of neurites per explant; A: the age expressed in gestational days; A epsilon [G23-G30]; G23 signifying gestational day 23, or P0). The observed age-related decrease of outgrowth could not be explained by progressive myelination of the spinal cord white matter, nor by the absence of trophic support from muscle, but may be related to a progressive inability of the spinal neurites to interact with collagen.

Foot Orgasm Syndrome: A Case Report in a Woman

INTRODUCTION Spontaneous orgasm triggered from inside the foot has so far not been reported in medical literature. AIMS The study aims to report orgasmic feelings in the left foot of a woman. METHODS A woman presented with complaints of undesired orgasmic sensations originating in her left foot. In-depth interview, physical examination, sensory testing, magnetic resonance imaging (MRI-scan), electromyography (EMG), transcutaneous electrical nerve stimulation (TENS), and blockade of the left S1 dorsal root ganglion were performed. MAIN OUTCOME MEASURES The main outcomes are description of this clinical syndrome, results of TENS application, and S1 dorsal root ganglion blockade. RESULTS Subtle attenuation of sensory amplitudes of the left suralis, and the left medial and lateral plantar nerve tracts was found at EMG. MRI-scan disclosed no foot abnormalities. TENS at the left metatarso-phalangeal joint-III of the left foot elicited an instant orgasmic sensation that radiated from plantar toward the vagina. TENS applied to the left side of the vagina elicited an orgasm that radiated to the left foot. Diagnostic blockade of the left S1 dorsal root ganglion with 0.8 mL bupivacaine 0.25 mg attenuated the frequency and intensity of orgasmic sensation in the left foot with 50% and 80%, respectively. Additional therapeutic blockade of the same ganglion with 0.8 mL bupivacaine 0.50 mg combined with pulsed radiofrequency treatment resulted in a complete disappearance of the foot-induced orgasmic sensations. CONCLUSION Foot orgasm syndrome (FOS) is descibed in a woman. Blockade of the left S1 dorsal root ganglion alleviated FOS. It is hypothesized that FOS, occurring 1.5 years after an intensive care emergency, was caused by partial nerve regeneration (axonotmesis), after which afferent (C-fiber) information from a small reinnervated skin area of the left foot and afferent somatic and autonomous (visceral) information from the vagina on at least S1 spinal level is misinterpreted by the brain as being solely information originating from the vagina.

Peripheral nervous system topics

*Adopts standard nomenclature following the new scheme by Paxinos, Watson, and Puelles and aligned with the Mai et al. Atlas of the Human Brain (new edition in 2007) * Provides essential reference information for users in conjunction with brain atlases for the identification of brain structures, the connectivity between different areas, and to evaluate data collected in anatomical, physiological, pharmacological, behavioural, and imaging studies. The book is an excellent companion to the Atlas of the Human Brain, and a common nomenclature throughout the book is enforced. Physiological data, functional concepts, and correlates to the neuroanatomy of the major model systems (rat and mouse) as well as brain function round out the new edition.

Spinal cord transections in fetal rats. Open intrauterine surgery with low mortality

Open myelotomies were performed in rat fetuses in stages E15-E19 with a microsurgical technique. To prevent oligohydramnios, considered to be one of the main causes of death associated with fetal surgery, amniotic fluid loss was reduced as much as possible. With this technique a reduction of the mortality rate to 38% was reached in 75 consecutive fetuses.