@article {70215, title = {Signatures of remote planning in hippocampal replay}, journal = {bioRxiv}, year = {2025}, month = {2025 Dec 04}, abstract = {

During brief, intermittent {\textquotedblleft}replay{\textquotedblright} events, hippocampal activity can express navigational trajectories disconnected from both when and where they originally occurred. While replay biased toward immediate future goals has been observed, there is no evidence yet linking replay to planning beyond the next action. Here, we designed a sequential spatial working memory task which required rats to utilize information across multiple temporally separated actions. Remote replay events matched the animal{\textquoteright}s future navigational choices made after completing an intervening subtask. Critically, this occurred only when the replayed information was useful for reducing memory load, consistent with it being an active process. Our findings suggest these remote replay events are a neural correlate of episodic forethought, allowing animals to use memories to plan beyond their immediate surroundings.

}, doi = {10.64898/2025.12.02.691753}, url = {https://www.biorxiv.org/content/early/2025/12/04/2025.12.02.691753}, author = {Lustig, Brian and Wang, Yingxue and Romani, Sandro and Pastalkova, Eva and Lee, Albert K.} } @article {47916, title = {Synchronized excitability in a network enables generation of internal neuronal sequences.}, journal = {eLife}, volume = {5}, year = {2016}, month = {2016 Sep 28}, abstract = {

Hippocampal place field sequences are supported by sensory cues and network internal mechanisms. In contrast, sharp-wave (SPW) sequences, theta sequences and episode-field sequences are internally generated. The relationship of these sequences to memory is unclear. SPW sequences have been shown to support learning and have been assumed to also support episodic memory. Conversely, we demonstrate these SPW sequences were present even after episodic memory in trained rats was impaired and after other internal sequences - episode-field and theta sequences - were eliminated. SPW sequences did not support memory despite continuing to {\textquoteright}replay{\textquoteright} all task-related sequences - place-field and episode-field sequences. Sequence replay occurred selectively during a synchronous increase of population excitability -- SPWs. Similarly, theta sequences depended on the presence of repeated synchronized waves of excitability - theta oscillations. Thus, we suggest that either intermittent or rhythmic synchronized changes of excitability trigger sequential firing of neurons, which in turn supports learning and/or memory.

}, issn = {2050-084X}, doi = {10.7554/eLife.20697}, author = {Yingxue, Wang and Roth, Zachary and Pastalkova, Eva} } @article {47124, title = {Clique topology reveals intrinsic geometric structure in neural correlations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {112}, year = {2015}, month = {2015 Nov 3}, pages = {13455-60}, abstract = {

Detecting meaningful structure in neural activity and connectivity data is challenging in the presence of hidden nonlinearities, where traditional eigenvalue-based methods may be misleading. We introduce a novel approach to matrix analysis, called clique topology, that extracts features of the data invariant under nonlinear monotone transformations. These features can be used to detect both random and geometric structure, and depend only on the relative ordering of matrix entries. We then analyzed the activity of pyramidal neurons in rat hippocampus, recorded while the animal was exploring a 2D environment, and confirmed that our method is able to detect geometric organization using only the intrinsic pattern of neural correlations. Remarkably, we found similar results during nonspatial behaviors such as wheel running and rapid eye movement (REM) sleep. This suggests that the geometric structure of correlations is shaped by the underlying hippocampal circuits and is not merely a consequence of position coding. We propose that clique topology is a powerful new tool for matrix analysis in biological settings, where the relationship of observed quantities to more meaningful variables is often nonlinear and unknown.

}, issn = {1091-6490}, doi = {10.1073/pnas.1506407112}, author = {Giusti, Chad and Pastalkova, Eva and Curto, Carina and Itskov, Vladimir} } @article {46924, title = {Oscillatory patterns in hippocampus under light and deep isoflurane anesthesia closely mirror prominent brain states in awake animals.}, journal = {Hippocampus}, volume = {26}, year = {2015}, month = {2015 Jul 18}, pages = {102-9}, abstract = {

The hippocampus exhibits a variety of distinct states of activity under different conditions. For instance the rhythmic patterns of activity orchestrated by the theta oscillation during running and REM sleep are markedly different from the large irregular activity (LIA) observed during awake resting and slow wave sleep. We found that under different levels of isoflurane anesthesia activity in the hippocampus of rats displays two distinct states which have several qualities that mirror the theta and LIA states. These data provide further evidence that the two states are intrinsic modes of the hippocampus; while also characterizing a preparation that could be useful for studying the natural activity states in hippocampus. This article is protected by copyright. All rights reserved.

}, issn = {1098-1063}, doi = {10.1002/hipo.22494}, author = {Lustig, Brian and Wang, Yingxue and Pastalkova, Eva} } @article {45792, title = {Theta sequences are essential for internally generated hippocampal firing fields.}, journal = {Nature Neuroscience}, volume = {18}, year = {2015}, month = {2015 Feb}, pages = {282-8}, abstract = {

Sensory cue inputs and memory-related internal brain activities govern the firing of hippocampal neurons, but which specific firing patterns are induced by either of the two processes remains unclear. We found that sensory cues guided the firing of neurons in rats on a timescale of seconds and supported the formation of spatial firing fields. Independently of the sensory inputs, the memory-related network activity coordinated the firing of neurons not only on a second-long timescale, but also on a millisecond-long timescale, and was dependent on medial septum inputs. We propose a network mechanism that might coordinate this internally generated firing. Overall, we suggest that two independent mechanisms support the formation of spatial firing fields in hippocampus, but only the internally organized system supports short-timescale sequential firing and episodic memory.

}, issn = {1546-1726}, doi = {10.1038/nn.3904}, author = {Wang, Yingxue and Romani, Sandro and Lustig, Brian and Leonardo, Anthony and Pastalkova, Eva} } @article {2341, title = {Cell assembly sequences arising from spike threshold adaptation keep track of time in the hippocampus.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {31}, year = {2011}, month = {2011 Feb 23}, pages = {2828-34}, abstract = {

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.

}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Itskov, Vladimir and Curto, Carina and Pastalkova, Eva and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2342, title = {Temporal delays among place cells determine the frequency of population theta oscillations in the hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {107}, year = {2010}, month = {2010 Apr 27}, pages = {7957-62}, abstract = {

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.

}, keywords = {Action Potentials, Animals, Hippocampus, Locomotion, Models, Neurological, Pyramidal Cells, Rats, Theta Rhythm}, issn = {1091-6490}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Geisler, Caroline and Diba, Kamran and Pastalkova, Eva and Mizuseki, Kenji and Royer, S{\'e}bastien and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2344, title = {Enemy avoidance task: a novel behavioral paradigm for assessing spatial avoidance of a moving subject.}, journal = {Journal of Neuroscience Methods}, volume = {180}, year = {2009}, month = {2009 May 30}, pages = {29-33}, abstract = {

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.

}, keywords = {Animal, Animals, Avoidance Learning, Behavior, Behavioral Sciences, Exploratory Behavior, Fear, Long-Evans, Male, Memory, Motor Activity, Movement, Neuropsychological Tests, Neuropsychology, Orientation, Psychomotor Performance, Rats, Space Perception}, issn = {1872-678X}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Telensky, Petr and Svoboda, Jan and Pastalkova, Eva and Blahna, Karel and Bures, Jan and Stuchlik, Ales} } @article {2343, title = {Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop.}, journal = {Neuron}, volume = {64}, year = {2009}, month = {2009 Oct 29}, pages = {267-80}, abstract = {

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.

}, keywords = {Action Potentials, Animals, Electric Stimulation, Entorhinal Cortex, Hippocampus, Long-Evans, Long-Term Potentiation, Male, Models, Movement, Nerve Net, Neural Inhibition, Neural Pathways, Neurological, Neurons, Patch-Clamp Techniques, Rats, Reaction Time, Synaptic Transmission, Theta Rhythm}, issn = {1097-4199}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Mizuseki, Kenji and Sirota, Anton and Pastalkova, Eva and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2347, title = {Induction of muscle thermogenesis by high-fat diet in mice: association with obesity-resistance.}, journal = {American Journal of Physiology. Endocrinology and Metabolism}, volume = {295}, year = {2008}, month = {2008 Aug}, pages = {E356-67}, abstract = {

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.

}, keywords = {Aminoimidazole Carboxamide, AMP-Activated Protein Kinases, Animals, Basal Metabolism, Body Temperature, Body Weight, Calorimetry, Dietary Fats, Fatty Acids, Inbred C57BL, Indirect, Male, Mice, Multienzyme Complexes, Muscle, Newborn, Nonesterified, Obesity, Oxygen Consumption, Protein-Serine-Threonine Kinases, Random Allocation, Ribonucleotides, Skeletal, Thermogenesis, Triglycerides}, issn = {0193-1849}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Kus, Vladimir and Prazak, Tomas and Brauner, Petr and Hensler, Michal and Kuda, Ondrej and Flachs, Pavel and Janovska, Petra and Medrikova, Dasa and Rossmeisl, Martin and Jilkova, Zuzana and Stefl, Bohumir and Pastalkova, Eva and Drahota, Zdenek and Houstek, Josef and Kopecky, Jan} } @article {2345, title = {Internally generated cell assembly sequences in the rat hippocampus.}, journal = {Science}, volume = {321}, year = {2008}, month = {2008 Sep 5}, pages = {1322-7}, abstract = {

A long-standing conjecture in neuroscience is that aspects of cognition depend on the brain{\textquoteright}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.

}, keywords = {Action Potentials, Animal, Animals, Behavior, Choice Behavior, Cues, Hippocampus, Interneurons, Long-Evans, Male, Maze Learning, Memory, Mental Recall, Models, Motor Activity, Neurological, Pyramidal Cells, Rats}, issn = {1095-9203}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Pastalkova, Eva and Itskov, Vladimir and Amarasingham, Asohan and Buzs{\'a}ki, Gy{\"o}rgy} } @article {2346, title = {Theta-mediated dynamics of spatial information in hippocampus.}, journal = {The Journal of Neuroscience: The Official Journal of the Society for Neuroscience}, volume = {28}, year = {2008}, month = {2008 Jun 4}, pages = {5959-64}, abstract = {

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{\textquoteright}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{\textquoteright}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.

}, keywords = {Action Potentials, Animals, Hippocampus, Long-Evans, Male, Rats, Spatial Behavior, Theta Rhythm}, issn = {1529-2401}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Itskov, Vladimir and Pastalkova, Eva and Mizuseki, Kenji and Buzs{\'a}ki, Gy{\"o}rgy and Harris, Kenneth D} } @article {2348, title = {Storage of spatial information by the maintenance mechanism of LTP.}, journal = {Science}, volume = {313}, year = {2006}, month = {2006 Aug 25}, pages = {1141-4}, abstract = {

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.

}, keywords = {Animals, Avoidance Learning, Conditioning (Psychology), Dentate Gyrus, Electric Stimulation, Excitatory Postsynaptic Potentials, Heat-Shock Proteins, Hippocampus, Long-Evans, Long-Term Potentiation, Male, Memory, Perforant Pathway, Protein Kinase C, Rats, Staurosporine, Time Factors}, issn = {1095-9203}, doi = {10.1523/JNEUROSCI.3773-10.2011}, author = {Pastalkova, Eva and Serrano, Peter and Pinkhasova, Deana and Wallace, Emma and Fenton, Andr{\'e} Antonio and Sacktor, Todd Charlton} } @article {3086, title = {Tetrodotoxin infusions into the dorsal hippocampus block non-locomotor place recognition.}, journal = {Hippocampus}, volume = {15}, year = {2005}, month = {2005 Mar 2}, pages = {460-71}, abstract = {

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.

}, keywords = {Anesthetics, Animal, Animals, Behavior, Disease Models, Feeding Behavior, Hippocampus, Local, Long-Evans, Male, Memory, Memory Disorders, Orientation, Rats, Space Perception, Tetrodotoxin}, issn = {1050-9631}, doi = {10.1002/hipo.20072}, author = {Klement, Daniel and Pastalkova, Eva and Fenton, Andr{\'e} A} } @article {2349, title = {Object-location memory impairment in patients with thermal lesions to the right or left hippocampus.}, journal = {Neuropsychologia}, volume = {42}, year = {2004}, month = {2004 Feb 25}, pages = {1017-28}, abstract = {

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.

}, keywords = {Adult, Anterior Temporal Lobectomy, Brain Damage, Brain Mapping, Cerebral, Chronic, Dominance, Electrocoagulation, Epilepsy, Female, Hippocampus, Humans, Male, Memory, Mental Recall, Middle Aged, Orientation, Pattern Recognition, Postoperative Complications, Reference Values, Short-Term, Temporal Lobe, Visual}, issn = {0028-3932}, doi = {10.1016/j.neuropsychologia.2004.01.002}, author = {Stepankova, Katerina and Fenton, Andr{\'e} A and Pastalkova, Eva and Kalina, Miroslav and Bohbot, V{\'e}ronique D} } @article {2350, title = {A battery of tests for quantitative examination of idiothetic and allothetic place navigation modes in humans.}, journal = {Behavioural Brain Research}, volume = {147}, year = {2003}, month = {2003 Dec 17}, pages = {95-105}, abstract = {

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.

}, keywords = {Adult, Cues, Exploratory Behavior, Female, Humans, Locomotion, Male, Memory, Orientation, Space Perception, Spatial Behavior}, issn = {0166-4328}, doi = {10.1016/S0166-4328(03)00141-4}, author = {Stepankova, Katerina and Pastalkova, Eva and Kalova, Eva and Kalina, Miroslav and Bures, Jan} }