Ventromedial Tracts Research Articles

Equine Degenerative Myeloencephalopathy in Lusitano Horses

Equine degenerative myeloencephalopathy (EDM) is a neurodegenerative disorder that has been previously associated with low vitamin E concentrations. To describe the clinical, electrophysiologic, and pathologic features of EDM in a group of related Lusitano horses. Fifteen Lusitano horses. Neurologic examinations were conducted, and serum vitamin E concentrations were measured. Three neurologically abnormal horses were further evaluated by ophthalmologic examination, electroretinography, electroencephalography, muscle and nerve biopsies, and post-mortem examination. Six horses appeared neurologically normal, 6 were neurologically abnormal, and 3 had equivocal gait abnormalities. Abnormal horses demonstrated ataxia and paresis. An inconsistent menace response was noted in 4 neurologically abnormal horses and in 1 horse with equivocal findings. All horses had low serum vitamin E concentrations (<1.5 ppm). Ophthalmologic examinations, electroretinograms, electroencephalograms, and muscle and peripheral nerve biopsies were unremarkable in 3 neurologically abnormal horses. At necropsy, major neuropathological findings in these horses were bilaterally symmetric, severe, neuro axonal degeneration in the gracilis, cuneatus medialis, cuneatus lateralis, and thoracicus nuclei and bilaterally symmetric axonal loss and demyelination mainly in the dorsolateral and ventromedial tracts of the spinal cord. A diagnosis of EDM was made based on these findings. Pedigree analysis identified 2 sires among the affected horses. Equine degenerative myeloencephalopathy is a neurodegenerative disorder that causes ataxia and, in severe cases, paresis, in young Lusitano horses. The disease appears to have a genetic basis, and although vitamin E deficiency is a common finding, low serum vitamin E concentrations also may occur in apparently unaffected related individuals.

NADPH-diaphorase histochemistry in the terminal abdominal ganglion of the crayfish.

Nitric oxide (NO) has an important modulatory role on the processing of sensory signals in vertebrates and invertebrates. In this investigation we studied the potential sources of NO in the terminal abdominal ganglion of the crayfish, Pacifastacus leniusculus, using NADPH-diaphorase (NADPHd) histochemistry, with NADPHd acting as a marker for NO synthase (NOS). In the terminal ganglion a mean of 27 strongly labelled NADPHd-positive cell bodies were found, and of these 80% [of stained cell bodies] [corrected] occurred in three regions located in antero-lateral, central and posterior parts of the ganglion. Ventral and antero-ventral commissures as well as specific dorsal and ventral areas of the dendritic neuropil showed positive staining. Intense labelling was seen in the ventro-medial tract, and in the connective between the terminal ganglion and the 5th abdominal ganglion. In addition, some motor neurones and neurones with branches in the sensory commissures were NADPHd positive. Our finding that NADPHd-positive cells occur in consistent patterns in the terminal abdominal ganglion implies that NO may have a role in mechanosensory processing in the crayfish.

Synaptic and nonsynaptic monoaminergic neuron systems in the lamprey spinal cord.

In the lamprey spinal cord, dopamine- (DA) and 5-hydroxytryptamine-(5-HT) containing cells appear to play an important role in controlling the firing properties of motoneurons and interneurons and, thereby, in modulating the efferent motor pattern. To determine the detailed morphology and synaptic connectivity of the intraspinal DA and 5-HT systems in Lampetra fluviatilis and Ichthyomyzon unicuspis, DA and 5-HT antisera were used in light and electron microscopic immunocytochemical experiments. Two main groups of labeled cells were distinguished: DA-containing liquor-contacting (LC) cells distributed along the central canal, and 5-HT+DA-containing multipolar cells located near the midline ventral to the central canal. Both types were synaptically connected with other neuronal elements. The DA-immunoreactive LC cells, which extended a ciliated process into the central canal, received symmetrical synapses from unlabeled terminals containing small synaptic vesicles. The distal process of the LC cells could be traced to the lateral cell column, to the ventral aspect of the dorsal column, or to the ventromedial area. Ultrastructural analysis of DA fibers in these regions showed the presence of labeled terminals containing numerous small synaptic vesicles and a few dense-core vesicles. These terminals formed symmetrical synapses with unlabeled cell bodies and dendrites, with GABA-immunopositive LC cells, and with the multipolar DA+5-HT cells. The multipolar DA+5-HT cells also received input from unlabeled synapses. Intracellular recording from these cells showed that they received excitatory postsynaptic potentials in response to stimulation of fibers in the ventromedial tracts and dorsal roots. The terminals of the multipolar DA+5-HT neurons in the ventromedial spinal cord contained numerous dense-core vesicles and small synaptic vesicles, but no synaptic specializations could be detected. In addition, a small number of larger DA-immunoreactive cells were observed in the lateral cell column at rostral levels. The lamprey spinal cord thus contains distinct populations of synaptically interconnected monoaminergic neurons. Dopamine-containing LC cells synapse onto DA+5-HT-containing multipolar cells, in addition to GABAergic LC cells and unidentified spinal neurons. In contrast, the multipolar cells appear to exert their influence by nonsynaptic mechanisms.

The sensory projections of Drosophila mutants which show abnormal wing formation or flying behavior

The central projection pattern of sensory neurones from the wing of Drosophila melanogaster arise from a small number of differencentiated entiated cell types which are localized in a pricise and reproducible spatial pattern. We report here the distribution of the nerve pathways revealed by filling with peroxidase and the structure and number of the wing sensory receptors, in files which have wings but which nevetheless are flightless, including one which presents abnormal wing formation. Our results indicate that in dumpy and taxi mutants, there are no detectable modifications in the neural projections or in the number and morphology of sensory receptors. Vestigial mutants however, present several alterations including the absence of the ovoid projection, a fact consistent with the existence of very few marginal bristles. The projection of the large campaniform sensilla branch profusely along the ventromedial tract and more sensory fibers cross the midline in the mesothorax. Wings of vestigial mutants show a decrease in the number of large campaniform sensilla, and more importantly some receptors present abnormally oriented trichomes in the neighboring cells.

The central projections of mesothoracic sensory neurons in wild-type Drosophila and bithorax mutants

Sensory axons entering the CNS from large campaniform sensilla on the normal, mesothoracic wings of four-winged flies of the genotype bx 3pbx Ubx 130 follow the same two tracts as do the corresponding axons in wild-type flies. However, they produce more branches along the ventromedial tract (including some in the mesothoracic neuromere), more fibers crossing the midline in the metathorax, and several other modifications of the wild-type pattern. No morphological differences between the receptors in normal and mutant flies could be detected, even with the SEM. The extra branching and other altered characteristics are present in bithorax flies which are also genetically wingless and do not form the homeotic appendages, so they appear to be due to the bx 3pbx Ubx 130 or bx 3 Ubx 130 genotype and not to some effect of the axons from the homeotic wings.

Ultrastructural Studies of the Dying-Back Process

A companion paper in this issue (46) described the evolution of peripheral nervous system dying-back disease of the giant axonal type in animals chronically intoxicated with the neurotoxic hexacarbons n-hexane (CH3CH2CH2CH2CH2CH3), methyl n-butyl ketone or MBK (CH3COCH2CH2CH2CH3), and 2,5-hexanedione (CH3COCH2CH2COCH3). The present study compares the distribution and pattern of peripheral (PNS) and central nervous system (CNS) dying-back disease produced by these three neurotoxic hexacarbons with that produced by acrylamide (CH2CHCONH2), and, in addition, employs these compounds to address unresolved issues in the dying-back process. In the PNS, large myelinated fibers in tibial nerve branches supplying calf muscles were especially sensitive in rats intoxicated with hexacarbons. These nerve branches and sensory plantar nerves in the hindfeet were equally vulnerable in acrylamide-treated rats. In both conditions, fibers located at these sites commenced degeneration before the distal regions of much longer and smaller diameter nerve fibers in nerve branches supplying the flexor digitorum brevis muscle and, in rats intoxicated with hexacarbons, before equivalent regions of plantar sensory branches to the digits. Pacinian corpuscles sited in the hindfeet of intoxicated cats were much less vulnerable to MBK than to acrylamide. Rats and cats intoxicated with hexacarbons displayed giant axonal swellings in vulnerable regions of the PNS degeneration in these animals was accompanied by pronounced endoneurial edema. In the CNS, rostral regions of long, ascending tracts (dorso-spino-cerebellar, gracile and, later, the cuneate) and the caudal end of long, descending tracts (lateral colums, ventrolateral and ventromedial tracts) of hexacarbon-treated animals were especially vulnerable. After prolonged intoxication of cats with MBK, giant axonal swelling was also found in preterminal and terminal axons in Rexed laminae V-VII at spinal levels C4 through S3-Neurofilament proliferation without giant axonal swelling was seen in CNS fibers of rats intoxicated with acrylamide. Taken in concert, the findings underline the importance of axon diameter and length in determining the hierarchy of fiber vulnerability and indicate the common sensitivity of selected regions of the PNS and CNS. The term central-peripheral distal axonopathy is introduced to emphasize the widespread, distal distribution of disease in these and in similar experimental conditions. It is suggested that certain human neuropathies (toxic, nutritional, uremic, diabetic and some hereditary polyneuropathies, and the neuropathy associated with multiple myeloma) are additional examples of central-peripheral distal axonopathies.

Reticulospinal influences on segmental neurons inLampetra fluviatilis

By recording the activity of single Muller's axons extra- and intracellularly, the electrical properties of fibers of the descending tract were determined during stimulation of the vestibular system, optic nerve, and spinal cord. The amplitude of the action potentials (APs) is 60–80 mv, their duration 3 msec, the highest frequency of responses to rythymic stimulation 170–250/sec, and the velocity of conduction of excitation is 5.4±0.4 m/sec along fibers of the ventromedial tract and 2.4±0.4 m/see in the lateral tract. These velocities remain unchanged over segments of the spinal cord up to 20 cm long. In response to stimulation of the descending tract by single pulses, only 1 AP is generated in Muller's axons whatever the strength of stimulation. In response to synaptic stimulation of Muller's neurons, discharges of regular frequency and duration are generated in axons of the descending tract just as in the neurons themselves. Transmission of excitation from Muller's axons to segmental motoneurons can take place with segmental delay of less than 1–3 msec, indicating the existence of mono-synaptic connections between these structures. Motoneuron activity in response to stimulation of the descending tract consists of generation of 1–6 APs at intervals of 7–20 msec. The suggestion that there are connections between one motoneuron and several Muller's axons is discussed.

Ultrastructural changes in central nerve fiber of the hen

The neurotoxic effects of tricresylphosphate on the ventromedial tract of the spinal cord in hens was examined with light and electron microscopy. Degenerative changes at the ultrastructural level of these myelinated fibers were correlated with the results obtained by light microscopy. The fine-structural changes were first noted in the form of swelling and loss of internal cristae of mitochondria, followed by shrinkage and disappearance of neurofilaments in the axoplasm, and finally the disintegration of myelin sheath itself. We suggest that a full axonal flow is more important for the maintenance of normal myelin sheath than the local integrity of the neuroglia cells.