Motor preparation of spatially and temporally defined movements: Evidence from startle

This article is available open access through the publisher’s website at the link below. Copyright © 2011 the American Physiological Society.Previous research has shown that the preparation of a spatially targeted movement performed at maximal speed is different from that of a temporally constrained movement (Gottlieb et al. 1989b). In the current study, we directly examined preparation differences in temporally vs. spatially defined movements through the use of a startling stimulus and manipulation of the task goals. Participants performed arm extension movements to one of three spatial targets (20°, 40°, 60°) and an arm extension movement of 20° at three movement speeds (slow, moderate, fast). All movements were performed in a blocked, simple reaction time paradigm, with trials involving a startling stimulus (124 dB) interspersed randomly with control trials. As predicted, spatial movements were modulated by agonist duration and timed movements were modulated by agonist rise time. The startling stimulus triggered all movements at short latencies with a compression of the kinematic and electromyogram (EMG) profile such that they were performed faster than control trials. However, temporally constrained movements showed a differential effect of movement compression on startle trials such that the slowest movement showed the greatest temporal compression. The startling stimulus also decreased the relative timing between EMG bursts more for the 20° movement when it was defined by a temporal rather than spatial goal, which we attributed to the disruption of an internal timekeeper for the timed movements. These results confirm that temporally defined movements were prepared in a different manner from spatially defined movements and provide new information pertaining to these preparation differences

Protection of flunarizine on cerebral mitochondria injury induced by cortical spreading depression under hypoxic conditions

A rat cortical spreading depression (CSD) model was established to explore whether cerebral mitochondria injury was induced by CSD under both normoxic and hypoxic conditions and whether flunarizine had a protective effect on cerebral mitochondria. SD rats, which were divided into seven groups, received treatment as follows: no intervention (control Group I); 1 M NaCl injections (Group II); 1 M KCl injections (Group III); intraperitoneal flunarizine (3 mg/kg) 30 min before KCl injections (Group IV); 14% O2 inhalation before NaCl injections (Group V); 14% O2 inhalation followed by KCl injections (Group VI); 14% O2 inhalation and intraperitoneal flunarizine followed by KCl injections (Group VII). Following treatment, brains were removed for the analysis of mitochondria transmembrane potential (MMP) and oxidative respiratory function after recording the number, amplitude and duration of CSD. The duration of CSD was significantly longer in Group VI than that in Group III. The number and duration of CSD in Group VII was significantly lower than that in Group VI. MMP in Group VI was significantly lower than that in Group III, and MMP in Group VII was significantly higher than that in Group VI. State 4 respiration in Group VI was significantly higher than that in Group III, and state 3 respiration in Group VII was significantly higher than that in Group VI. Respiration control of rate in Group VII was also significantly higher than that in Group VI. Thus, we concluded that aggravated cerebral mitochondria injury might be attributed to CSD under hypoxic conditions. Flunarizine can alleviate such cerebral mitochondria injury under both normoxic and hypoxic conditions

Reproducibility of histopathological findings in experimental pathology of the mouse: a sorry tail

Reproducibility of $\textit{in vivo}$ research using the mouse as a model organism depends on many factors, including experimental design, strain or stock, experimental protocols, and methods of data evaluation. Gross and histopathology are often the endpoints of such research and there is increasing concern about the accuracy and reproducibility of diagnoses in the literature. To reproduce histopathological results, the pathology protocol, including necropsy methods and slide preparation, should be followed by interpretation of the slides by a pathologist familiar with reading mouse slides and familiar with the consensus medical nomenclature used in mouse pathology. Likewise, it is important that pathologists are consulted as reviewers of manuscripts where histopathology is a key part of the investigation. The absence of pathology expertise in planning, executing and reviewing $\textit{in vivo}$ research using mice leads to questionable pathology-based findings and conclusions from studies, even in high-impact journals. We discuss the various aspects of this problem, give some examples from the literature and suggest solutions.This work was supported in part by US National Institutes of Health grants R01 AR049288, CA089713 and R21 AR063781 (to J.P.S.) and by The Warden and Fellows of Robinson College, Cambridge (to P.N.S.)

Does administration of non-steroidal anti-inflammatory drug determine morphological changes in adrenal cortex: ultrastructural studies

Rofecoxib (Vioxx© made by Merck Sharp & Dohme, the USA) is a non-steroidal anti-inflammatory drug which belongs to the group of selective inhibitors of cyclooxygenasis-2, i.e., coxibs. Rofecoxib was first registered in the USA, in May 1999. Since then the drug was received by millions of patients. Drugs of this group were expected to exhibit increased therapeutic action. Additionally, there were expectations concerning possibilities of their application, at least as auxiliary drugs, in neoplastic therpy due to intensifying of apoptosis. In connection with the withdrawal of Vioxx© (rofecoxib) from pharmaceutical market, attempts were made to conduct electron-microscopic evaluation of cortical part of the adrenal gland in preparations obtained from animals under influence of the drug. Every morning animals from the experimental group (15 rats) received rofecoxib (suspension in physiological saline)—non-steroidal anti-inflammatory drug (Vioxx©, Merck Sharp and Dohme, the USA), through an intragastric tube in the dose of 1.25 mg during 8 weeks. In the evaluated material, there was found a greater number of secretory vacuoles and large, containing cholesterol and other lipids as well as generated glucocorticoids, lipid drops in cytoplasm containing prominent endoplasmic reticulum. There were also found cells with cytoplasm of smaller density—especially in apical and basal parts of cells. Mitochondria occasionally demonstrated features of delicate swelling. The observed changes, which occurred on cellular level with application of large doses of the drug, result from mobilization of adaptation mechanisms of the organism

Long-term control by corticosteroids of the inward rectifier in rat CA1 pyramidal neurons, in vitro

In this study we examined long-lasting effects mediated by intracellular mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) on two voltage dependent potassium conductances in CA1 pyramidal neurons, i.e. the transient current I(A) and the delayed rectifier, and on the inward rectifier I(Q), a mixed sodium/potassium current. All experiments were carried out in hippocampal slices with the in situ patch clamp technique, in the whole cell mode. Neurons recorded 30 min to 3 h after a brief application of 30 nM corticosterone to slices from adrenalectomized rats, thus saturating MRs and occupying most of the GRs, displayed a large I(Q)-conductance similar to neurons in slices from the sham-operated controls. By contrast, if only MRs or only GRs were activated, the I(Q)-conductance was significantly smaller than for the corticosterone-treated group of cells, indicating that simultaneous activation of both MRs and GRs is necessary to achieve a large I(Q)-conductance. If corticosterone was applied in the presence of a protein synthesis inhibitor, the I(Q) conductance was significantly smaller than in the absence of the inhibitor. Properties of the I(A) and the delayed rectifier were not affected by the various corticosteroid treatments. In conclusion, the data indicate that in particular the I(Q)-conductance is under a gene-mediated control of corticosteroid hormones. The I(Q)-conductance is relatively low when only MRs are activated, as occurs for the rat in the morning under rest, and high when both MRs and GRs are occupied, as occurs at the peak of the circadian cycle and after stress. This finding suggests that MR- and GR-mediated events act in synergism to control the I(Q), thus contributing to regulation of cellular excitability under physiologically relevant conditions