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18 Publications

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    Pastalkova Lab
    08/01/08 | Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance.
    Kus V, Prazak T, Brauner P, Hensler M, Kuda O, Flachs P, Janovska P, Medrikova D, Rossmeisl M, Jilkova Z, Stefl B, Pastalkova E, Drahota Z, Houstek J, Kopecky J
    American Journal of Physiology. Endocrinology and Metabolism. 2008 Aug;295(2):E356-67. doi: 10.1523/JNEUROSCI.3773-10.2011

    The obesogenic effect of a high-fat (HF) diet is counterbalanced by stimulation of energy expenditure and lipid oxidation in response to a meal. The aim of this study was to reveal whether muscle nonshivering thermogenesis could be stimulated by a HF diet, especially in obesity-resistant A/J compared with obesity-prone C57BL/6J (B/6J) mice. Experiments were performed on male mice born and maintained at 30 degrees C. Four-week-old mice were randomly weaned onto a low-fat (LF) or HF diet for 2 wk. In the A/J LF mice, cold exposure (4 degrees C) resulted in hypothermia, whereas the A/J HF, B/6J LF, and B/6J HF mice were cold tolerant. Cold sensitivity of the A/J LF mice was associated with a relatively low whole body energy expenditure under resting conditions, which was normalized by the HF diet. In both strains, the HF diet induced uncoupling protein-1-mediated thermogenesis, with a stronger induction in A/J mice. Only in A/J mice: 1) the HF diet augmented activation of whole body lipid oxidation by cold; and 2) at 30 degrees C, oxygen consumption, total content, and phosphorylation of AMP-activated protein kinase (AMPK), and AICAR-stimulated palmitate oxidation in soleus muscle was increased by the HF diet in parallel with significantly increased leptinemia. Gene expression data in soleus muscle of the A/J HF mice indicated a shift from carbohydrate to fatty acid oxidation. Our results suggest a role for muscle nonshivering thermogenesis and lipid oxidation in the obesity-resistant phenotype of A/J mice and indicate that a HF diet could induce thermogenesis in oxidative muscle, possibly via the leptin-AMPK axis.

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    Pastalkova Lab
    06/04/08 | Theta-mediated dynamics of spatial information in hippocampus.
    Itskov V, Pastalkova E, Mizuseki K, Buzsáki G, Harris KD
    The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 2008 Jun 4;28(23):5959-64. doi: 10.1523/JNEUROSCI.3773-10.2011

    In rodent hippocampus, neuronal activity is organized by a 6-10 Hz theta oscillation. The spike timing of hippocampal pyramidal cells with respect to the theta rhythm correlates with an animal’s position in space. This correlation has been suggested to indicate an explicit temporal code for position. Alternatively, it may be interpreted as a byproduct of theta-dependent dynamics of spatial information flow in hippocampus. Here we show that place cell activity on different phases of theta reflects positions shifted into the future or past along the animal’s trajectory in a two-dimensional environment. The phases encoding future and past positions are consistent across recorded CA1 place cells, indicating a coherent representation at the network level. Consistent theta-dependent time offsets are not simply a consequence of phase-position correlation (phase precession), because they are no longer seen after data randomization that preserves the phase-position relationship. The scale of these time offsets, 100-300 ms, is similar to the latencies of hippocampal activity after sensory input and before motor output, suggesting that offset activity may maintain coherent brain activity in the face of information processing delays.

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    Pastalkova Lab
    08/25/06 | Storage of spatial information by the maintenance mechanism of LTP.
    Pastalkova E, Serrano P, Pinkhasova D, Wallace E, Fenton AA, Sacktor TC
    Science. 2006 Aug 25;313(5790):1141-4. doi: 10.1523/JNEUROSCI.3773-10.2011

    Analogous to learning and memory storage, long-term potentiation (LTP) is divided into induction and maintenance phases. Testing the hypothesis that the mechanism of LTP maintenance stores information requires reversing this mechanism in vivo and finding out whether long-term stored information is lost. This was not previously possible. Recently however, persistent phosphorylation by the atypical protein kinase C isoform, protein kinase Mzeta (PKMz), has been found to maintain late LTP in hippocampal slices. Here we show that a cell-permeable PKMz inhibitor, injected in the rat hippocampus, both reverses LTP maintenance in vivo and produces persistent loss of 1-day-old spatial information. Thus, the mechanism maintaining LTP sustains spatial memory.

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    Pastalkova Lab
    03/02/05 | Tetrodotoxin infusions into the dorsal hippocampus block non-locomotor place recognition.
    Klement D, Pastalkova E, Fenton AA
    Hippocampus. 2005 Mar 2;15(4):460-71. doi: 10.1002/hipo.20072

    The hippocampus is critical for navigation in an open field. One component of this navigation requires the subject to recognize the target place using distal cues. The experiments presented in this report tested whether blocking hippocampal function would impair open field place recognition. Hungry rats were trained to press a lever on a feeder for food. In Experiment 1, they were passively transported with the feeder along a circular trajectory. Lever pressing was reinforced only if the feeder was passing through a 60 degrees -wide sector. Thus, rats preferentially lever pressed in the vicinity of the reward sector indicating that they recognized its location. Tetrodotoxin (TTX) infusions aimed at the dorsal hippocampi caused rats to substantially increase lever pressing with no preference for any region. The aim of Experiment 2 was to determine whether the TTX injections caused a loss of place recognition or a general increase of lever pressing. A separate group of rats was conditioned in a stationary apparatus to press the lever in response to a light. The TTX injections did not abolish preferential lever pressing in response to light. Lever pressing increased less than half as much as the TTX-induced increase in Experiment 1. When these animals with functional hippocampi could not determine the rewarded period because the light was always off, lever pressing increased much more and was similar to the TTX-induced increase in Experiment 1. We conclude that the TTX inactivation of the hippocampi impaired the ability to recognize the reward place.

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    Pastalkova Lab
    02/25/04 | Object-location memory impairment in patients with thermal lesions to the right or left hippocampus.
    Stepankova K, Fenton AA, Pastalkova E, Kalina M, Bohbot VD
    Neuropsychologia. 2004 Feb 25;42(8):1017-28. doi: 10.1016/j.neuropsychologia.2004.01.002

    Memory for object-location was investigated by testing subjects with small unilateral thermolesions to the medial temporal lobe using small-scale 2D (Abstract) or large-scale 3D (Real) recall conditions. Four patients with lesions of the left hippocampus (LH), 10 patients with damage to the right hippocampus (RH) and 9 matched normal controls (NC) were tested. Six task levels were presented in a pseudorandom order. During each level, subjects viewed one to six different objects on the floor of a circular curtained arena 2.90 m in diameter for 10 s. Recall was tested by marking the locations of objects on a map of the arena (Abstract recall) and then by replacing the objects in the arena (Real recall). Two component errors were studied by calculating the Location Error (LE), independent of the object identity and the configuration error by finding the best match to the presented configuration. The RH group was impaired relative to the NC for nearly all combinations of recall and error types. An impairment was observed in this group even for one object and it deepened sharply with an increasing object number. Damage to the right perirhinal or parahippocampal cortices did not add to the impairment. Deficits in the LH group were also observed, but less consistently. The data indicate that spatial memory is strongly but not exclusively lateralised to the right medial temporal lobe.

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    Pastalkova Lab
    12/17/03 | A battery of tests for quantitative examination of idiothetic and allothetic place navigation modes in humans.
    Stepankova K, Pastalkova E, Kalova E, Kalina M, Bures J
    Behavioural Brain Research. 2003 Dec 17;147(1-2):95-105. doi: 10.1016/S0166-4328(03)00141-4

    Research into the neural mechanisms of place navigation in laboratory animals has led to the definition of allothetic and idiothetic navigation modes that can be examined by quantitative analysis of the generated tracks. In an attempt to use this approach in the study of human navigation behavior, 10 young subjects were examined in an enclosed arena (2.9 m in diameter, 3 m high) equipped with a computerized tracking system. Idiothetic navigation was studied in blindfolded subjects performing the following tasks-Simple Homing, Complex Homing and Idiothesis Supported by Floor-Related Signals. Allothetic navigation was examined in sighted subjects instructed to find in an empty arena the acoustically signaled unmarked goal region and later to retrieve its position using tasks (Natural Navigation, Cue-Controlled Navigation, Snapshot Memory, Map Reading) that evaluated different aspects of allothesis. The results indicate that allothetic navigation is more accurate than idiothetic, that the poor accuracy of idiothesis is due to angular rather than to distance errors, and that navigation performance is best when both allothetic and idiothetic modes contribute to the solution of the task. The proposed test battery may contribute to better understanding of the navigation disturbances accompanying various neurological disorders and to objective evaluation of the results of drug therapy and of rehabilitation procedures.

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    Pastalkova LabKeleman Lab
    02/18/03 | Operant behavior can be triggered by the position of the rat relative to objects rotating on an inaccessible platform.
    Pastalkova E, Kelemen E, Bures J
    Proceedings of the National Academy of Sciences of the United States of America. 2003 Feb 18;100(4):2094-9. doi: 10.1073/pnas.0438002100

    The present study describes a task testing the ability of rats to trigger operant behavior by their relative spatial position to inaccessible rotating objects. Rats were placed in a Skinner box with a transparent front wall through which they could observe one or two adjacent objects fixed on a slowly rotating arena (d = 1 m) surrounded by an immobile black cylinder. The direction of arena rotation was alternated at a sequence of different time intervals. Rats were reinforced for the first bar-press that was emitted when a radius separating the two adjacent objects or dividing a single object into two halves (pointing radius) entered a 60 degrees sector of its circular trajectory defined with respect to the stationary Skinner box (reward sector). Well trained rats emitted 62.1 +/- 3.6% of responses in a 60 degrees sector preceding the reward sector and in the first 30 degrees of the reward sector. Response rate increased only when the pointing radius was approaching the reward sector, regardless of the time elapsed from the last reward. In the extinction session, when no reward was delivered, rats responded during the whole passage of the pointing radius through the former reward sector and spontaneously decreased responding after the pointing radius left this area. This finding suggests that rats perceived the reward sector as a continuous single region. The same results were obtained when the Skinner box with the rat was orbiting around the immobile scene. It is concluded that rats can recognize and anticipate their position relative to movable objects.

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    Pastalkova Lab
    01/23/99 | Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides.
    Koroleva VI, Korolev OS, Mares V, Pastalkova E, Bures J
    Brain Research. 1999 Jan 23;816:618-27

    A model of acute carbon monoxide poisoning combined with spreading depression (SD) induced metabolic stress was used to examine the protective effects of cerebrolysin (CL) on the development of electrophysiological, behavioral and morphological signs of hypoxic damage. Capillary electrodes were implanted into the neocortex and hippocampus of anesthetized rats which were then exposed for 90 min to breathing of 0.8% to 0.5% CO, while 3 to 4 waves of cortical and hippocampal SD were elicited by microinjections of 5% KCl. Duration of SD-provoked depolarization of cerebral cortex and hippocampus was noted. Nine and 18 to 19 days later propagation of SD waves was recorded with the same electrodes and decrease of their amplitude was used as an index of brain damage which was significant in the hippocampus but not in the cortex. CL-treatment (2.5 ml/kg per day) started after CO administration and continued for 14 days significantly improved hippocampal recovery manifested by increased amplitude of SD waves. Behavioral tests performed 10 and 20 days after CO poisoning in the Morris water maze revealed better performance (escape latency 7 s) in the CL-treated than in untreated animals (14 s). Morphological analysis showed marked damage in the hippocampus consonant with electrophysiological and behavioral findings in the same animals. No apparent histological damage was found in rats exposed to CO inhalation alone without the additional SD-provoked depolarization. It is concluded that chronic CL-treatment enhances recovery of hippocampal tissue after hypoxic damage of intermediate severity.

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