Spinal motoneurones

Figure 2.13 Relation between the action potential recorded intracellularly from a cat spinal motoneuron following antidromic stimulation (int.) and the local field potential recorded with an extracellular electrode (ext.). (Adapted from Terzuolo, AC and Araki, T (1961) Ann. NY Acad. Sci. 94 547-558). Published by NYAS...

The dendrites of neurons adjacent to those which degenerate also show extensive growth and sprouting which could facilitate abnormal and disorganised synaptic transmission and cause hyperactivity. It is also known that the dendrites of cells around an alumina focus in monkeys, as well as in human epileptic brain, lose their spinous processes, which might contribute to the paroxysmal discharge by facilitating the spread of depolarisation to the neuron soma. Certainly an increase in the number of Na+ channels on the dendrites of spinal motoneurons, which would facilitate the occurrence of reactive dendritic Na+ spikes, has been seen after axotomy. 

Kmjevic, K., and Lisiewicz, A. (1972) Injections of calcium ions into spinal motoneurons. J. Physiol., 225 363-390. 

Konishi, S. and Otsuka, M. Excitatory action of hypothalamic substance P on spinal motoneurons of newborn rats, Nature 1974, 252, 734-735. 

Lu, Y. Y. et al. (2003). Intramuscular injection of AAV-GDNF results in sustained expression of transgenic GDNF, and its delivery to spinal motoneurons by retrograde transport. Neurosci. Res. 45(1), 33-40. 

Martinov, V. N. et al. (2002). Targeting functional subtypes of spinal motoneurons and skeletal muscle fibers in vivo by intramuscular injection of adenoviral and adeno-associated viral vectors. Anat. Embryol. (Berk) 205(3), 215-221. 

Of particular interest is a structure-activity study carried out by Shirahama and co-workers which has revealed an order of depolarizing activity as assayed in the newborn rat spinal motoneuron for the naturally occurring kainoids and synthetic analogues shown in Figure 7.31 (Note Figure 7 refers to the kainoid 1 having a cis relative disposition of the C-3 and C-4 substituents.)... 

Novel kainate derivatives potent depolarizing actions on spinal motoneurones and dorsal root fibres in newborn rats. 

Hughes, R. A., Sendtner, M., Goldfarb, M., Lindholm, D., and Thoenen, H., Evidence that fibroblast growth factor 5 is a major muscle-derived survival factor for cultured spinal motoneurons, Neuron, 10, 369, 1993. 

Holstege JC (1991) Ultrastructural evidence for GABAergic brain stem projections to spinal motoneurons in the rat. J Neurosci // 159-167. 

Holstege JC, Bongers CMH (1991) A glycinergic projection from the ventromedial lower brainstem to spinal motoneurons. An ultrastructural double labeling study in the rat. Brain Res 566 308-315. 

Meister B, Arvidsson U, Zhang X, Jacobsson G, Villar MJ, Hokfelt T (1993) Glutamate transporter mRNA and glutamate-like immunoreactivity in spinal motoneurones. Neurorepon 5 337-340. 

Turkanis SA, Karler R (1983) Effects of delta 9-tetrahydrocannabinol on cat spinal motoneurons. Brain Res 288 283-287... 

Turkanis SA, Karler R (1986) Cannabidiol-caused depression of spinal motoneuron responses in cats. Pharmacol Biochem Behav 25 89-94... 

Drugs That Reduce the Tonic Output of Primary Spinal Motoneurons... 

In vivo administration of CNTF prevents degeneration of chick spinal motoneurons during development (Op-penheim et al., 1991) and motor neurons are known to... 

Cell death of spinal motoneurons in the chick embryo following deafferentation rescue effects of tissue extracts, soluble proteins, and neurotrophic agents. J. Neurosci. 14 1619-1 MO. 

Murphy et al. (1991) were the first to report that CDF/LIF exerts neurotrophic effects in developing sensory neurons (DRG). CDF/LIF also exerts neurotrophic effects on spinal motoneurons and nodose ganglia neurons (Martinou et al., 1992 Henderson et al., 1993 Thaler et al, 1994). Furthermore, both CNTF and CDF/LIF stimulate survival of spinal motoneurons in vivo... 

Very limited amounts of immunoreactive a-MSH are found in spinal motoneurons and motor endplates of skeletal muscle in normal, healthy adult animals but this is increased considerably in young rodents, in adults with inherited muscular dystrophy or motoneurone disease, or following nerve injury (Haynes and Smith, 1985 Hughes and Smith, 1989b). 

Piehl, F., Arvidsson, U., Johnson, H., Cullheim, S., Dagerlind, A., Ulfhake, B., Cao, Y., Elde, R., Pettersson, R.F., Teren-ius, L. et al. (1993) GAP-43, aFGF, CCK and alpha-CGRP and beta-CGRP in rat spinal motoneurons subjected to axotomy andJor dorsal root severance. Eur. J. Neurosci. 5 1321-1333. 

Pu, S.-F., Zhuang, H.-X., Marsh, D.J. and Ishii, D.N. (1995b) Insulin-like growth factor is required for spinal motoneuron survival following sciatic nerve axotomy. Soc. Neurosci. Abstr. 21 1789. 

Mechanism of action The spasmolytic drugs act by several mechanisms. Three of the drugs act in the spinal cord. Diazepam facilitates GABA-mediated presynaptic inhibition, and baclofen acts as a GABAg agonist. Tizanidine, an imidazoline related to clonidine, reinforces both presynaptic and postsynaptic inhibition in the cord. All three drugs reduce the tonic output of the primary spinal motoneurons. 

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