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Cerebellar Purkinje cells of mormyrid fish differ in some morphological as well as physiological parameters from their counterparts in mammals. Morphologically, Purkinje cells of mormyrids have larger dendrites that are characterized by a lower degree of branching in the molecular layer. Physiologically, there are differences in electrophysiological response patterns that are related to sodium channel activity: first, sodium spikes in mormyrid Purkinje cells have low amplitudes, typically not exceeding 30 mV. Second, the response to climbing fiber stimulation in mormyrid Purkinje cells does not consist of a complex spike (with an initial fast sodium spike) as in mammals, but instead it consists of an all-or-none excitatory postsynaptic potential, the so-called climbing fiber response. Because of these unique properties, we have begun to characterize mormyrid Purkinje cells electrophysiologically. In this study, we provide a description of voltage-gated Na+ channels and conductances in Purkinje cells of the mormyrid fish Gnathonemus petersii. Various types of Na+ channel alpha-subunits, i.e., Nav1.1, Nav1.2, and Nav1.6, have been described in rodent Purkinje cells. Using immunohistochemical techniques, we found that these subunits are present in Purkinje cells of mormyrids. To test whether these Na+ channel subunits can mediate fast inactivating and resurgent Na+ currents in Gnathonemus Purkinje cells, we conducted patch-clamp recordings in acutely dissociated cells and in cerebellar slices. Both types of Na+ currents could be measured in rat and fish Purkinje cells. These data show that, despite prominent differences in electrophysiological response characteristics, Purkinje cells of rats and mormyrids share the same voltage-gated Na+ conductances. [ABSTRACT FROM AUTHOR]

The neurophysiology of the rodent visual system has mainly been investigated by invasive and ex-vivo techniques providing fragmented data. This area of research has been deprived of functional MRI studies based on blood oxygenation level dependent (BOLD) contrast, which allows a whole brain approach with a high spatial and temporal resolution. In the present study, we looked at the neurovascular response properties of the visual system of the pigmented rat, focusing on the visual cortex (VC), the superior colliculus (SC) and the flocculus-paraflocculus of the cerebellum (FL-PFL), using BOLD fMRI under domitor anesthesia. Visual stimulation was performed monocularly or binocularly while flashing light from a strobe unit was presented. For each structure, we assessed the flashing frequency that evoked the optimal BOLD response: Neither the VC nor the FL-PFL displayed frequency dependence during monocular visual stimulation, but were most sensitive to low frequencies (1-5 Hz) when flashing light was provided binocularly. The SC responded optimally to high flashing rates (8-12 Hz) during both monocular and binocular stimulation. The signal intensity changes in the VC and FL-PFL were locked to the stimulation period, whereas the BOLD response in the SC showed a similar onset but a very slow recovery at offset. The VC and FL-PFL, but not the SC, showed signs of binocular competition. The observed correlation between frequency-dependent responses of different visual areas during binocular visual presentation suggests a functional relationship between the VC and FL-PFL rather than between the SC and FL-PFL. [ABSTRACT FROM AUTHOR]

According to the multisensory integration theory vestibular, optokinetic and proprioceptive inputs act in concert to maintain a stable retinal image of the visual world. Yet, it remains elusive to what extent the otolith organs contribute to this process and whether a specific loss of otolith input is compensated for. Here we investigated the compensatory eye movements in tilted mice, which lack otoconia because of a mutation in otopetrin 1. Tilted mice showed very small displacements of the eyes in the orbit during static roll paradigms, suggesting the absence of functional otolith organs. Independent of head position with respect to gravity, the gain and phase lead of angular vestibuloocular reflex of tilted mice were decreased and increased, respectively (frequencies 0.2 to 1 Hz and peak accelerations 8 to 197 degrees /s2, respectively). Furthermore, lack of otolith input increases the dependency of the vestibular system on stimulus frequency. In contrast, the gain of optokinetic reflex in tilted mice was significantly higher in the low-frequency range than in control mice, regardless of the position of the mice in space or the plane of the eye movements. To explain these results, a simple model was used in which a multisensory integration unit was embedded. With this model, we were able to simulate all the behaviors observed. Thus our data and the model support the presence of the multisensory integration system and revealed a compensatory enhanced optokinetic reflex in tilted mice, indicating an adaptive synergism in the processing of otolith and visually driven signals. [ABSTRACT FROM AUTHOR]

ABSTRACTThe aim of this study was to investigate the underlying mechanisms of the increased gains of the cervico-ocular reflex (COR) and the lack of synergy between the COR and the vestibulo-ocular reflex (VOR) that have been previously observed in patients with whiplash-associated disorders (WAD). Eye movements during COR or VOR stimulation were recorded in four different experiments. The effect of restricted neck motion and the relationship between muscle activity and COR gain was examined in healthy controls. The adaptive ability of the COR and the VOR was tested in WAD patients and healthy controls. Reduced neck mobility yielded an increase in COR gain. No correlation between COR gain and muscle activity was observed. Adaptation of both the COR and VOR was observed in healthy controls, but not in WAD patients. The increased COR gain of WAD patients may stem from a reduced neck mobility. The lack of adaptation of the two stabilization reflexes may result in a lack of synergy between them. These abnormalities may underlie several of the symptoms frequently observed in WAD, such as vertigo and dizziness. [ABSTRACT FROM AUTHOR]

Most people with Williams syndrome (WS) have a heterozygous 1.55 Mb deletion on chromosome 7q11.23. For diagnostic purposes, fluorescence in situhybridisation (FISH) with commercial FISH probes is commonly used to detect this deletion. We investigated whether multiplex ligation-dependent probe amplification (MLPA) is a reliable alternative for FISH. The MLPA kit (SALSA P029) contains probes for eight genes in the WS critical region FKBP6, FZD9, TBL2, STX1A, ELN, LIMK1, RFC2, and CYLN2. The experimental FISH assay that was used consists of four probes covering the WS critical region. A total number of 63 patients was tested; in 53 patients, a deletion was detected both with FISH and MLPA(P029), in 10 patients both techniques failed to demonstrate a deletion. In only one patient, a deletion was detected which was not previously detected by two commercial FISH probes. This patient appeared to carry a small, atypical deletion. We conclude that MLPA is a reliable technique to detect WS. Compared with FISH, MLPA is less time consuming and has the possibility to detect also smaller, atypical deletions and duplications in the WS critical region. [ABSTRACT FROM AUTHOR]

Mice carrying mutations of the gene encoding the ion pore of the P/Q calcium channel (Cacna1a) are an instance in which cerebellar dysfunction may be attributable to altered electrophysiology and thus provide an opportunity to study how neuronal intrinsic properties dictate signal processing in the ocular motor system. P/Q channel mutations can engender multiple effects at the single neuron, circuit, and behavioral levels; correlating physiological and behavioral abnormalities in multiple allelic strains will ultimately facilitate determining which alterations of physiology are responsible for specific behavioral aberrations. We used videooculography to quantify ocular motor behavior in tottering mutants aged 3 mo to 2 yr and compared their performance to data previously obtained in the allelic mutant rocker and C57BL/6 controls. Tottering mutants shared numerous abnormalities with rocker, including upward deviation of the eyes at rest, increased vestibuloocular reflex (VOR) phase lead at low stimulus frequencies, reduced VOR gain at high stimulus frequencies, reduced gain of the horizontal and vertical optokinetic reflex, reduced time constants of the neural integrator, and reduced plasticity of the VOR as assessed in a cross-axis training paradigm. Unlike rocker, young tottering mutants exhibited normal peak velocities of nystagmus fast phases, arguing against a role for neuromuscular transmission defects in the attenuation of compensatory eye movements. Tottering also differed by exhibiting directional asymmetries of the gains of optokinetic reflexes. The data suggest at least four pathophysiological mechanisms (two congenital and two acquired) are required to explain the ocular motor deficits in the two Cacna1a mutant strains. [ABSTRACT FROM AUTHOR]

The epistatic circler mouse (Ecl mouse) is a preexisting mutant, which displays a circling phenotype and hyperactivity. It has been shown that the circling phenotype in this mutant results from a complex inheritance pattern, but the vestibular pathology has not been analyzed. The present study deals with the morphological and functional basis responsible for the circling behavior in the Ecl mouse. Morphological examination of the inner ears revealed a bilateral malformation of the horizontal (lateral) semicircular canal and duct. No cochlear abnormalities were detected, and auditory brainstem response (ABR) measurements indicated that the auditory system is not affected. Investigation of the vestibuloocular reflex (VOR) in Ecl mice showed that their horizontal VOR on stimulation is virtually absent, which correlates with the morphological findings. J. Comp. Neurol. 468:587–595, 2004. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Bicaudal D is an evolutionarily conserved protein, which is involved in dynein-mediated motility both in Drosophila and in mammals. Here we report that the N-terminal portion of human Bicaudal D2 (BICD2) is capable of inducing microtubule minus end-directed movement independently of the molecular context. This characteristic offers a new tool to exploit the relocalization of different cellular components by using appropriate targeting motifs. Here, we use the BICD2 N-terminal domain as a chimera with mitochondria and peroxisome-anchoring sequences to demonstrate the rapid dynein-mediated transport of selected organelles. Surprisingly, unlike other cytoplasmic dynein-mediated processes, this transport shows very low sensitivity to overexpression of the dynactin subunit dynamitin. The dynein-recruiting activity of the BICD2 N-terminal domain is reduced within the full-length molecule, indicating that the C-terminal part of the protein might regulate the interaction between BICD2 and the motor complex. Our findings provide a novel model system for dissection of the molecular mechanism of dynein motility. [ABSTRACT FROM AUTHOR]