Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor

During development of the nervous system, neurons in many regions are overproduced by proliferation, after which the excess cells are eliminated by cell death. The survival of only a proportion of neurons during normal development is thought to be regulated by the limited availability of neurotrophic agents. One such putative trophic agent is ciliary neurotrophic factor (CNTF), a polypeptide that promotes the survival of ciliary, sensory, and sympathetic neurons in vitro. In contrast to the results of in vitro studies, however, the daily treatment of chick embryos in vivo with purified human recombinant CNTF failed to rescue any of these cell populations from cell death, whereas CNTF did promote the in vivo survival of spinal motoneurons. Thus, CNTF may not act as a neurotrophic agent in vivo for those embryonic neurons (especially ciliary neurons) on which it acts in vitro. Rather, CNTF may be required for in vivo survival of motoneurons.     

Morphine-induced delay of normal cell death in the avian ciliary ganglion

Repeated administration of morphine in increasing doses delayed normal cell death in the ciliary ganglion of the chick embryo; the effect was completely blocked by naloxone. Survival of spinal motoneurons was not affected. Morphine also inhibited potassium-stimulated synthesis of acetylcholine in ganglion cells cultured with muscle, suggesting that morphine can influence neurotransmission. Morphine's effect on cell death may be due to an inhibition of transmission at the neuromuscular junction, but opiates may also directly affect cell death. Although it is now known whether the endogenous opiates in the ciliary ganglion influence neuronal survival during embryogenesis, exogenous opiates can affect normal cell death in the autonomic nervous system.     

成年大鼠面神经低位切断后面运动神经元的死亡进程及GDNF的保护作用

目的 观察大鼠面神经低位切断伤后,大鼠面运动神经元死亡的时间进程和胶质细胞源性神经营养因子(GDNF)局部应用对伤后面运动神经元的作用.方法 手术制作大鼠右侧面神经的低位切断伤 GDNF模型,左侧为切断伤 PBS液对照.用HE、甲苯胺蓝染色技术观测面运动神经元死亡情况及其形态学变化.结果 面神经低位切断伤可引起面运动神经元死亡且于伤后4周时达到高峰.损伤后1、2、4、6周时,GDNF侧神经元数量明显多于对照侧(P＜0.01).伤后2、4、6周时,GDNF侧的神经元数量较第1周时均减少(P＜0.01),而第4周与第6周的神经元数量差异无统计学意K(P＞0.05).结论 局部应用GDNF对低位切断伤后的面运动神经元有显著的保护作用,这种作用在损伤4周内完全发挥.     

Androgens prevent normally occurring cell death in a sexually dimorphic spinal nucleus

The spinal nucleus of the bulbocavernosus (SNB) contains many more motoneurons in adult male rats than in females. Androgens establish this sex difference during a critical perinatal period, which coincides with normally occurring cell death in the SNB region. Sex differences in SNB motoneuron number arise primarily because motoneuron loss is greater in females than in males during the early postnatal period. Perinatal androgen treatment in females attenuates cell death in the SNB region, reducing motoneuron loss to levels typical of males. The results suggest that steroid hormones determine sex differences in neuron number by regulating normally occurring cell death and that the timing of this cell death may therefore define critical periods for steroid effects on neuron number.     

Reduction of naturally occurring motoneuron death in vivo by a target-derived neurotrophic factor

Treatment of chick embryos in ovo with crude and partially purified extracts from embryonic hindlimbs (days 8 to 9) during the normal cell death period (days 5 to 10) rescues a significant number of motoneurons from degeneration. The survival activity of partially purified extract was dose-dependent and developmentally regulated. The survival of sensory, sympathetic, parasympathetic, and a population of cholinergic sympathetic preganglionic neurons was unaffected by treatment with hindlimb extract. The massive motoneuron death that occurs after early target (hindlimb) removal was partially ameliorated by daily treatment with the hindlimb extract. These results indicate that a target-derived neurotrophic factor is involved in the regulation of motoneuron survival in vivo.     

Androgens regulate the dendritic length of mammalian motoneurons in adulthood

Sex steroid hormones have been thought to alter behaviors in adulthood by changing the activity of neural circuits rather than by inducing major structural changes in these pathways. In a group of androgen-sensitive motoneurons that mediate male copulatory functions, decreases in androgen levels after castration of adult rats produced dramatic structural changes, decreasing both the dendritic length and soma size of these motoneurons. These changes were reversed by androgen replacement. These results imply a surprising degree of synaptic plasticity in adult motoneurons and suggest that normal changes in androgen levels in adulthood are associated with significant alterations in the structure and function of these neurons.     

Connectivity patterns of crayfish giant interneurons: visualization of synaptic regions with cobalt dye

Intracellular injection of cobalt dye was used to visualize electrical synapses between two pairs of central giant interneurons and giant motoneurons in the crayfish central nervous system. A pair of giant motoneurons in each ganglion contacts the interneurons, but not all contact points are functional synapses. Cobalt dye reveals numerous fine projections that are present at synaptic contact points and absent at nonsynaptic contacts; intracellular recording confirms this correlation. The different connectivity patterns of the two pairs of interneurons are consistent with the different behavior patterns which they evoke.     

Strychnine: its action on spinal motoneurons of cats

In cats strychnine does not alter measurably the potential, threshold, after potentials, or refractoriness of the membrane of the spinal motoneurons. Increased reflexes probably result from increase of excitatory impingement upon motoneurons. Spikes recorded during a rapid succession of nerve impulses produced by strychnine ("strychnine burst") suggest that soma membrane resistance is appreciable during stimulation.     

Hormonal control of the anatomical specificity of motoneuron-to-muscle innervation in rats

Motoneurons of the spinal nucleus of the bulbocavernosus innervate bulbocavernosus muscles in male rats. Adult female rats normally lack both the spinal nucleus and its target muscles. Prenatal treatment of females with testosterone propionate resulted in adults having, like males, both the spinal nucleus and its target muscles. However, prenatal treatment with dihydrotestosterone propionate preserves the muscles but not the motoneurons. This paradoxical condition might result from (i) bulbocavernosus muscles without innervation; (ii) muscles innervated by morphologically unrecognizable motoneurons; (iii) muscles innervated by a very few spinal nucleus cells, each innervating many bulbocavernosus fibers; or (iv) muscles innervated by motoneurons outside their normal anatomical locus in the spinal nucleus. The results of retrograde marker injections into the bulbocavernosus muscles of females treated with androgen refute the first three possibilities and confirm the last: the different androgen treatments result in anatomically distinct spinal motor nuclei innervating bulbocavernosus muscles.     

Development of hindlimb locomotor activity in the bullfrog (Rana catesbeiana) studied in vitro

The isolated central nervous system of the bullfrog larva (tadpole) is a valuable model system for studying the development of central motor control because the neural activity for locomotion is expressed in vitro. Patterned synaptic activation of immature hindlimb motoneurons is present before the bones and muscles of the hindlimb differentiate, and it develops against the background of the tadpole's functionally mature motor program for tail oscillations. This activation of hindlimb motoneurons later produces patterned bursting that underlies coordinated stepping and frog kicks.     

Intracellular study of recurrent facilitation

Recurrent facilitation in the cat's spinal cord has been studied in deep peroneal and quadriceps motoneurons with the use of intracellular recording. The presence of facilitation was indicated by several criteria, among them increased firing index of the cells or decreased latency of firing. In many, but not all, facilitated cells the conditioning volley caused a small visible depolarization. Subthreshold synaptic potentials were frequently increased in magnitude by the conditioning volley, which also increased the effectiveness of a stimulus applied through the microelectrode. Facilitation was found in a large percentage of the motoneurons investigated and was clearly able to bring about pronounced changes in the excitability and firing behavior of these cells.     

Newly identified 'glutamate interneurons' and their role in locomotion in the lamprey spinal cord

A new class of excitatory premotor interneurons that are important in the generation of locomotion in the lamprey has now been described. In the isolated spinal cord, these neurons act simultaneously with their postsynaptic motoneurons during fictive swimming. They are small and numerous, and they monosynaptically excite both motoneurons and inhibitory premotor interneurons. The excitatory postsynaptic potentials are depressed by an antagonist of excitatory amino acids. These interneurons receive reticulospinal input from the brain stem and polysynaptic input form skin afferents. A model of the network underlying locomotion based on the synaptic interactions of these neurons can now be proposed for the lamprey.     

Voltage clamp of motoneuron soma

Concentric microelectrodes were used to voltage-clamp spinal motoneurons. With depolarizing voltage steps, current transients often appear, with some latency and in all-or-none fashion. Voltage-current relations indicate a two- to threefold reduction in resistance between inside and outside when the cell fires. These results suggest that activity does not involve the whole soma-dendritic membrane.     

Excitatory and inhibitory motoneurons in the central nervous system of the leech

The locomotion and reflex responses of the leech are brought about by inmuscles that are arranged in a regular, simple pattern in the body wall and that flatten, shorten, lengthen, or bend the animal. In the segmental ganglia, it is possible to recognize by morphological and physiological criteria the individual motoneurons that cause contractions and relaxations of these muscles.     

Inhibition of neighboring motoneurons in conscious control of single spinal motoneurons

Multiple fine-wire electrodes were implanted in the biceps brachii of five subjects, and artificial electronic feedback was provided to subjects from only one electrode. By this technique, it was shown that neighboring units progressively stop firing as subjects concentrate on activating an isolated unit. The inhibition of neighboring spinal motoneurons in the same pool further indicates that selective inhibition is an automatic part of single motor-unit training.     

Primary afferent depolarization evoked by a painful stimulus

Pulses of intense radiant heat applied to the plantar pad of unanesthetized spinal cats produced negative dorsal root potentials, increased excitability of cutaneous A fibers, and marked activation of ipsilateral flexor motoneurons. The same effects were obtained during cold block of A fiber conduction in the appropriate peripheral nerve. We conclude that adequate noxious activation of cutaneous C fibers depolarizes cutaneous A fibers.     

Two gustatory systems: facial and vagal gustatory nuclei have different brainstem connections

The gustatory sense in catfish consists of two dissociable components, a facial nerve system used for food selection and a vagal nerve system involved in swallowing. Neural tracing experiments demonstrate that the primary sensory nucleus for the facial gustatory system is connected to the reticular formation and trigeminal nuclei. In contrast, the primary sensory nucleus for the vagal gustatory system is connected to the motoneurons that mediate swallowing. These results provide anatomical evidence for parallel gustatory systems within the vertebrate central nervous system.     

Ammonium and chloride extrusion: hyperpolarizing synaptic inhibition in spinal motoneurons

The reversal potential of postsynaptic inhibition shifts toward resting membrane potentials in cat spinal motoneurons after intravenous infusion of ammonium salts(1 to 3 millimoles per kilogram of body weight). Simultaneously, the depolarizing action of intracellularly injected chloride ions on the inhibitory membrane is enhanced and recovery therefrom is prolonged. Passive membrane properties remain unaltered. The results indicate a blocking of active extrusion of chloride which normally maintains a high ionic gradient for hyperpolarizing inhibition.     

Erratum

In the report "Alteration in connections between muscle and anterior horn motoneurons after peripheral nerve repair" by T. M. Brushart and M.-M. Mesulam (9 May, p. 603), the key to cell types in Fig. 1 was inadvertently omitted. The dashed lines refer to (A) right peroneal, (B to D) postoperative, and (E) peroneal cells. The solid lines refer to (A) left peroneal, (B to D) control, and (E) tibial cells.