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13 Publications

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    Pastalkova Lab
    02/23/11 | Cell assembly sequences arising from spike threshold adaptation keep track of time in the hippocampus.
    Itskov V, Curto C, Pastalkova E, Buzsáki G
    The Journal of Neuroscience: The Official Journal of the Society for Neuroscience. 2011 Feb 23;31(8):2828-34. doi: 10.1523/JNEUROSCI.3773-10.2011

    Hippocampal neurons can display reliable and long-lasting sequences of transient firing patterns, even in the absence of changing external stimuli. We suggest that time-keeping is an important function of these sequences, and propose a network mechanism for their generation. We show that sequences of neuronal assemblies recorded from rat hippocampal CA1 pyramidal cells can reliably predict elapsed time (15-20 s) during wheel running with a precision of 0.5 s. In addition, we demonstrate the generation of multiple reliable, long-lasting sequences in a recurrent network model. These sequences are generated in the presence of noisy, unstructured inputs to the network, mimicking stationary sensory input. Identical initial conditions generate similar sequences, whereas different initial conditions give rise to distinct sequences. The key ingredients responsible for sequence generation in the model are threshold-adaptation and a Mexican-hat-like pattern of connectivity among pyramidal cells. This pattern may arise from recurrent systems such as the hippocampal CA3 region or the entorhinal cortex. We hypothesize that mechanisms that evolved for spatial navigation also support tracking of elapsed time in behaviorally relevant contexts.

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    Pastalkova Lab
    04/27/10 | Temporal delays among place cells determine the frequency of population theta oscillations in the hippocampus.
    Geisler C, Diba K, Pastalkova E, Mizuseki K, Royer S, Buzsáki G
    Proceedings of the National Academy of Sciences of the United States of America. 2010 Apr 27;107(17):7957-62. doi: 10.1523/JNEUROSCI.3773-10.2011

    Driven either by external landmarks or by internal dynamics, hippocampal neurons form sequences of cell assemblies. The coordinated firing of these active cells is organized by the prominent "theta" oscillations in the local field potential (LFP): place cells discharge at progressively earlier theta phases as the rat crosses the respective place field ("phase precession"). The faster oscillation frequency of active neurons and the slower theta LFP, underlying phase precession, creates a paradox. How can faster oscillating neurons comprise a slower population oscillation, as reflected by the LFP? We built a mathematical model that allowed us to calculate the population activity analytically from experimentally derived parameters of the single neuron oscillation frequency, firing field size (duration), and the relationship between within-theta delays of place cell pairs and their distance representations ("compression"). The appropriate combination of these parameters generated a constant frequency population rhythm along the septo-temporal axis of the hippocampus, while allowing individual neurons to vary their oscillation frequency and field size. Our results suggest that the faster-than-theta oscillations of pyramidal cells are inherent and that phase precession is a result of the coordinated activity of temporally shifted cell assemblies, relative to the population activity, reflected by the LFP.

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    Pastalkova Lab
    10/29/09 | Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop.
    Mizuseki K, Sirota A, Pastalkova E, Buzsáki G
    Neuron. 2009 Oct 29;64(2):267-80. doi: 10.1523/JNEUROSCI.3773-10.2011

    Theta oscillations are believed to play an important role in the coordination of neuronal firing in the entorhinal (EC)-hippocampal system but the underlying mechanisms are not known. We simultaneously recorded from neurons in multiple regions of the EC-hippocampal loop and examined their temporal relationships. Theta-coordinated synchronous spiking of EC neuronal populations predicted the timing of current sinks in target layers in the hippocampus. However, the temporal delays between population activities in successive anatomical stages were longer (typically by a half theta cycle) than expected from axon conduction velocities and passive synaptic integration of feed-forward excitatory inputs. We hypothesize that the temporal windows set by the theta cycles allow for local circuit interactions and thus a considerable degree of computational independence in subdivisions of the EC-hippocampal loop.

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    Svoboda LabPastalkova Lab
    05/30/09 | Enemy avoidance task: a novel behavioral paradigm for assessing spatial avoidance of a moving subject.
    Telensky P, Svoboda J, Pastalkova E, Blahna K, Bures J, Stuchlik A
    Journal of Neuroscience Methods. 2009 May 30;180(1):29-33. doi: 10.1523/JNEUROSCI.3773-10.2011

    Navigation with respect to moving goals represents a useful ability in the everyday life of animals. We have developed a novel behavioral paradigm, "enemy avoidance task", in which a laboratory rat (subject) was trained to avoid another rat (enemy), while searching for small pasta pellets dispensed onto an experimental arena. Whenever the distance between the two animals was smaller than 25 cm, the subject was given a mild electric footshock. The results have shown that rats are capable of avoiding another rat while exploring an environment. Therefore, the enemy avoidance task can be used in electrophysiological, lesion or neuropharmacological studies exploring neuronal substrate coding for egocentric and allocentric positions of an observed animal.

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    Pastalkova Lab
    09/05/08 | Internally generated cell assembly sequences in the rat hippocampus.
    Pastalkova E, Itskov V, Amarasingham A, Buzsáki G
    Science. 2008 Sep 5;321(5894):1322-7. doi: 10.1523/JNEUROSCI.3773-10.2011

    A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain’s ability to self-generate sequential neuronal activity. We found that reliably and continually changing cell assemblies in the rat hippocampus appeared not only during spatial navigation but also in the absence of changing environmental or body-derived inputs. During the delay period of a memory task, each moment in time was characterized by the activity of a particular assembly of neurons. Identical initial conditions triggered a similar assembly sequence, whereas different conditions gave rise to different sequences, thereby predicting behavioral choices, including errors. Such sequences were not formed in control (nonmemory) tasks. We hypothesize that neuronal representations, evolved for encoding distance in spatial navigation, also support episodic recall and the planning of action sequences.

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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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