Effects of axotomy on lamprey spinal neurons

doi:10.1016/0014-4886(81)90210-7

Experimental Neurology

Volume 73, Issue 3, September 1981, Pages 750-761

https://doi.org/10.1016/0014-4886(81)90210-7 Get rights and content

Abstract

The central axonal processes of dorsal cells of larval sea lampreys were cut by a high spinal transection. Subsequent histologic changes included a loss of cytoplasmic basophilia, nuclear eccentricity, the development of a perinuclear basophilic shell, and a slight decrease in cell diameter and increase in nuclear diameter resulting in a 26% increase in the ratio of nucleus to cell diameter. These changes were maximal at 3 weeks and were related to the proximity of the cell to the transection site. Electrophysiologic changes included increased input resistance, increased voltage and current thresholds for spike initiation, decreased maximal rate of rise of action potentials, increased spike width, and increased spike overshoot. There was also an increase in axonal conduction velocity and a reduction in resting membrane potential. The electrophysiologic changes tended to lag behind the histologic changes by 1 to 2 weeks and were not clearly related to the proximity of the cell to the transection site. The cellular electrophysiologic changes could result from a decrease in the densities of sodium and potassium channels of the membrane, but there is no evidence yet to support this or any other specific hypothesis.

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Cited by (17)

Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey
2009, Experimental Neurology
The sea lamprey recovers normal-appearing locomotion after spinal cord transection and its spinal axons regenerate selectively in their correct paths. However, among identified reticulospinal neurons some are consistently bad regenerators and only about 50% of severed reticulospinal axons regenerate through the site of injury. We previously suggested (Shifman, M. I., and Selzer, M. E., 2000a. Expression of netrin receptor UNC-5 in lamprey brain; modulation by spinal cord transection. Neurorehabilitation and Neural Repair 14, 49–58; Shifman, M. I., and Selzer, M. E., 2000b. In situ hybridization in wholemounted lamprey spinal cord: localization of netrin mRNA expression. Journal of Neuroscience Methods 104, 19–25) that selective chemorepulsion might explain why some neurons are bad regenerators and others not. To explore the role of additional chemorepulsive axonal guidance molecules during regeneration, we examined the expression of the repulsive guidance molecule (RGM) and its receptor neogenin by in situ hybridization and quantitative PCR. RGM mRNA was expressed in the spinal cord, primarily in neurons of the lateral gray matter and in dorsal cells. Following spinal cord transection, RGM message was downregulated in neurons close (within 10 mm) to the transection at 2 and 4 weeks, although it was upregulated in reactive microglia at 2 weeks post-transection. Neogenin mRNA expression was unchanged in the brainstem after spinal cord transection, and among the identified reticulospinal neurons, was detected only in “bad regenerators”, neurons that are known to regenerate well never expressed neogenin. The downregulation of RGM expression in neurons near the transection may increase the probability that regenerating axons will regenerate through the site of injury and entered caudal spinal cord.
Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology
2001, Progress in Neurobiology
Among the advantages offered by the lamprey brainstem and spinal cord for studies of the structure and function of the nervous system is the unique identifiability of several pairs of reticulospinal neurons in the brainstem. These neurons have been exploited in investigations of the patterns of sensory input to these cells and the patterns of their outputs to spinal neurons, but no doubt these cells could be used much more effectively in exploring their roles in descending control of the spinal cord. The variability of cell positions of neurons in the spinal cord has precluded the recognition of unique spinal neurons. However, classes of nerve cells can be readily defined and characterized within the lamprey spinal cord and this has led to progress in understanding the cellular and synaptic mechanisms of locomotor activity. In addition, both the identifiable reticulospinal cells and the various spinal nerve cell classes and their known synaptic interactions have been used to demonstrate the degree and specificity of regeneration within the lamprey nervous system. The lack of uniquely identifiable cells within the lamprey spinal cord has hampered progress in these areas, especially in gaining a full understanding of the locomotor network and how neuromodulation of the network is accomplished.
Fluorescent tracers as potential candidates for double labeling of descending brain neurons in larval lamprey
1998, Journal of Neuroscience Methods
In larval lamprey, seven fluorescent tracers were tested as potential candidates for retrograde double labeling of descending brain neurons: Fluoro–Gold (FG); fluorescein dextran amine (FDA); True Blue (TB); cascade blue dextran amine (CBDA); Fast Blue (FB); Texas red dextran amine (TRDA); and tetramethylrhodamine dextran amine (RDA). The first tracer (FG, TB, FB, or CBDA) was applied to the spinal cord at 40% body length (BL). In separate experiments, the second tracer (TRDA or RDA) was applied to the spinal cord at 20% BL. The tracer combination FG/TRDA was found to have the best optical properties for double labeling. However, application of FG to the spinal cord with the method used for the other tracers resulted in labeling of ‘lateral cells’ along the sides of the rhombencephalon that were presumed to be non-neuronal and that obscured some of the descending brain neurons. Control experiments suggested that FG was transported in the circulation to the brain, where the tracer was taken up by lateral cells. Therefore, a special technique was developed for applying FG to the spinal cord without allowing the tracer to enter the circulation. In larval lamprey, this important double-labeling technique that was developed for TRDA and FG is being used to examine axonal regeneration and projection patterns of descending brain neurons.
Regeneration of supraspinal projection neurons in the adult goldfish
1993, Brain Research
Regeneration of descending supraspinal projections were identified in adult goldfish following administration of HRP to different levels of the spinal cord. While in the untreated normal fish 17 nuclei were shown to project into the spinal cord, only 11 of them seem to have participated in the process of regeneration. The nuclei whose axons regenerated include the nucleus ventromedialis (NVMD), nucleus of the median longitudinal fasciculus (NMLF), nucleus reticularis superior (NRS), nucleus reticularis medialis (NRM), nucleus reticularis inferior (NRI), anterior octaval nucleus (AON), magnocellular octaval nucleus (MON), descending octaval nucleus (DON) and certain neurons of the facial lobe. The neurons of the magnocellular preoptic nucleus (NPO), raphe nucleus (NR), Mauthner cell (MC), posterior octaval nucleus (PON) and somata located adjacent to the descending trigeminal tract were not labeled. The nuclei that apparently participated in the regeneration process were significantly larger in size than the corresponding cell bodies in the untreated normal fish.
Axotomy-induced alterations in the electrophysiological characteristics of neurons
1990, Progress in Neurobiology
The axon reaction of lamprey spinal interneurons
1987, Brain Research
Axotomy and partial denervation of giant interneurons (GIs) and lateral cells (LCs) were produced by complete spinal transection in the larval lamprey spinal cord. Both cell types demonstrated a reduction in cytoplasmic basophilia, increase in cell size, nuclear eccentricity, and formation of a chromophilic nuclear cap. This was quantified in the case of cell diameter. During the first 8 weeks of recovery, the GIs with the largest diameters were found progressively further from the scar and this peak change moved at approximately 0.5 mm/day. The increase in size of GIs remained up to 20 weeks post-transection, long after the time required for their axons to regenerate across the scar and form functioning synapses. GIs injected intracellularly with horseradish peroxidase (HRP) also showed this increase in diameter as well as a simplification of their dendritic trees. Intracellular recordings from GIs revealed changes in the frequency and amplitude of spontaneous synaptic input. In the first two weeks after transection, spontaneous excitatory postsynaptic potentials (EPSPs) and inhibitory postsynaptic potentials (IPSPs) were less frequent than in control cells. After 6 weeks of recovery they became more frequent than in control cells. EPSPs predominated in axotomized GIs, while in control cells they constituted only 36% of the total of spontaneous potentials. A reversible increase in the amplitude of these EPSPs occurred at 3–4 weeks of recovery time. The resting membrane potential was significantly reduced by the 6th week after transection and returned to normal after the 22nd week.

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¹: This work was supported by U.S. Public Health Service grants NS14257 and NS14837 and by National Institutes of Health Academic Career Development Award 5K07NS11083 to M. E. S.

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Experimental Neurology

Abstract

References (27)

Chromatolysis in a pair of identifiable metathoracic neurons in the cockroach, Diploptera punctata

Tissue Cell

Electrophysiologic and cyclic AMP changes in axon-transected frog spinal roots

Exp. Neurol.

Reflex activity of regenerating frog spinal motoneurons

Brain Res.

Selective synaptic changes following spinal motoneuron axotomy

Brain Res.

The axon reaction: a review of the principal features of perikarial responses to axon injury

Int. Rev. Neurobiol.

Changes in the morphology and amino acid incorporation of regenerating goldfish optic neurons

Exp. Neurol.

Variability in maps of identified neurons in the sea lamprey spinal cord examined by a wholemount technique

Brain Res.

Ultrastructural observations on retrograde atrophy of lateral geniculate body. 1. Neuronal Alterations

J. Neuropathol. Exp. Neurol.

Retrograde cellular changes in the mesencephalic trigeminal nucleus in the cat following cerebellar lesions

Acta Morphol. Neer-Scand.

Differential response of two neuron types to facial nerve transection in young and old rabbits

J. Neuropathol. Exp. Neurol.

Quantitative effects of the peripheral innervation area on nerves and spinal ganglion cells

J. Comp. Neurol.

Neurons of insects: RNA changes during injury and regeneration

Science

Changes in conduction velocity and fibre size proximal to peripheral nerve lesions

J. Physiol. (London)

Cited by (17)

Expression of the repulsive guidance molecule RGM and its receptor neogenin after spinal cord injury in sea lamprey

Contributions of identifiable neurons and neuron classes to lamprey vertebrate neurobiology

Fluorescent tracers as potential candidates for double labeling of descending brain neurons in larval lamprey

Regeneration of supraspinal projection neurons in the adult goldfish

Axotomy-induced alterations in the electrophysiological characteristics of neurons

The axon reaction of lamprey spinal interneurons