of cultured spinal motoneurons from presymptomatic ALS mice. J Neurophysiol 91: 571-575, 2004. First published October 1, 2003 10.1152/jn.00665.2003. ALS (amyotrophic lateral sclerosis) is an adult-onset and deadly neurodegenerative disease characterized by a progressive and selective loss of motoneurons. Transgenic mice overexpressing a mutated human gene (G93A) coding for the enzyme SOD1 (Cu/Zn superoxide dismutase) develop a motoneuron disease resembling ALS in humans. In this generally accepted ALS model, we tested the electrophysiological properties of individual embryonic and neonatal spinal motoneurons in culture by measuring a wide range of electrical properties influencing motoneuron excitability during current clamp. There were no differences in the motoneuron resting potential, input conductance, action potential shape, or afterhyperpolarization between G93A and control motoneurons. The relationship between the motoneuron's firing frequency and injected current (f-I relation) was altered. The slope of the f-I relation and the maximal firing rate of the G93A motoneurons were much greater than in the control motoneurons. Differences in spontaneous synaptic input were excluded as a cause of increased excitability. This finding identifies a markedly elevated intrinsic electrical excitability in cultured embryonic and neonatal mutant G93A spinal motoneurons. We conclude that the observed intrinsic motoneuron hyperexcitability is induced by the SOD1 toxic gain-of-function through an aberration in the process of action potential generation. This hyperexcitability may play a crucial role in the pathogenesis of ALS as the motoneurons were cultured from presymptomatic mice.
1. The two main types of lateral line organs of lower vertebrates are the superficial neuromasts (SN), with a cupula that protrudes in the surrounding water, and the canal neuromasts (CN), located in the lateral line canal. The scales of the trunk lateral line canal of fish contain SNs as well as CNs. In this study, we examine whether there exist two functional classes of afferent fibers in the trunk lateral line nerve of the rainbow trout that can be attributed to the SNs and CNs. 2. The response properties of the afferent fibers in the trunk lateral line nerve have been determined during stimulation with sinusoidally varying water motion generated by a small vibrating sphere. Linear frequency response analysis revealed the presence of two distinct populations of afferent fibers in the lateral line nerve. The fibers belonging to the two populations showed significant differences in the frequency at which the sensitivity was maximal, the low-frequency response slope and the low-frequency asymptotic phase angle. 3. One population of fibers has a maximum sensitivity at 36 +/- 13 (SD) Hz (n = 22) and responds up to this frequency to water velocity. The low-frequency slope of the frequency response of these fibers was 20 +/- 3 (SD) dB/decade and the low-frequency phase lead was 121 +/- 11 degrees (mean +/- SD), both with respect to sphere displacement. The fibers of the other population have a maximum sensitivity at 93 +/- 14 (SD) Hz (n = 12) and respond up to this frequency to water acceleration. The low-frequency slope of these fibers was 35 +/- 5 (SD) dB/decade, and the low-frequency phase lead was 188 +/- 13 degrees (mean +/- SD). 4. Analysis of the stochastic properties of the spontaneous activity of both types of fibers revealed that the mean firing rate of the fibers responding to water velocity (26 +/- 12 spikes/s, mean +/- SD; n = 22) was significantly higher than that of the fibers responding to acceleration (36 +/- 11 spikes/s, mean +/- SD; n = 12). The other statistical properties of the spontaneous activity were found to be indistinguishable. 5. From comparison of the results with the available quantitative data on frequency responses of lateral line organs in other species, it has been concluded that the fibers responding (< or = 40 Hz) to water velocity innervate SNs and that the fibers responding (< or = 90 Hz) to water acceleration innervate CNs.(ABSTRACT TRUNCATED AT 400 WORDS)
The stimulus response relation of the epidermal lateral-line organ of Xenopus laevis was studied by recording activity of single afferent nerve fibres in isolated preparations. Linear frequency response analysis over a frequency range of 0.1--100Hz was performed under steady-state conditions, using small amplitude, sinusoidal water displacements produced by a glass sphere at a short distance from the skin. Period histograms of afferent nerve activity were computed, and amplitude, phase and mean activity of the response were determined by means of Fourier analysis. A standardization procedure at the start of each experiment made scaling of the frequency responses of different preparations unnecessary. The results show that for small stimulus amplitudes the response of the lateral-line organ over the whole range of frequencies studied can adequately be described as a modulation of the spontaneous activity. The amplitude of the response is proportional to the stimulus amplitude, and the phase of the response is independent of stimulus amplitude. The lateral-line organ of Xenopus laevis can thus be regarded as a linear system for stimuli which produce modulation of the spontaneous activity. The frequency response demonstrates unequivocally that the lateral-line organ of Xenopus laevis functions as a water velocity detector. For frequencies of stimulation from 0.1--20Hz the gain increases with a slope of 7.5 dB/oct, and up to 5Hz the response is almost in phase with the water velocity. The extent to which the different transmission steps between stimulus and response will contribute to the frequency response is discussed.
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