Publications | Ulanovsky Lab

2024

Bats

Las L. & Ulanovsky N. (2024) Nature Methods 21, 1135-1137

Las2024.pdf

2023

Organization of projections from the entorhinal cortex to the hippocampal formation of the Egyptian fruit bat Rousettus aegyptiacus

Jacobsen B., Kleven H., Gatome W., Las L., Ulanovsky N. & Witter M. P. (2023) Hippocampus 33, 889-905

Jacobsen2023.pdf

The hippocampal formation and entorhinal cortex are crucially involved in learning and memory as well as in spatial navigation. The conservation of these structures across the entire mammalian lineage demonstrates their importance. Information on a diverse set of spatially tuned neurons has become available, but we only have a rudimentary understanding of how anatomical network structure affects functional tuning. Bats are the only order of mammals that have evolved true flight, and with this specialization comes the need to navigate and behave in a three dimensional (3D) environment. Spatial tuning of cells in the entorhinal-hippocampal network of bats has been studied for some time, but whether the reported tuning in 3D is associated with changes in the entorhinal-hippocampal network is not known. Here we investigated the entorhinal-hippocampal projections in the Egyptian fruit bat (Rousettus aegyptiacus), by injecting chemical anterograde tracers in the entorhinal cortex. Detailed analyses of the terminations of these projections in the hippocampus showed that both the medial and lateral entorhinal cortex sent projections to the molecular layer of all subfields of the hippocampal formation. Our analyses showed that the terminal distributions of entorhinal fibers in the hippocampal formation of Egyptian fruit bats-including the proximo-distal and longitudinal topography and the layer-specificity-are similar to what has been described in other mammalian species such as rodents and primates. The major difference in entorhinal-hippocampal projections that was described to date between rodents and primates is in the terminal distribution of the DG projection. We found that bats have entorhinal-DG projections that seem more like those in primates than in rodents. It is likely that the latter projection in bats is specialized to the behavioral needs of this species, including 3D flight and long-distance navigation.

Dissociating two aspects of human 3D spatial perception by studying fighter pilots

Ginosar G., Karpas E. D., Weitzner I. & Ulanovsky N. (2023) Scientific Reports 13, 11265.

Ginosar2023b.pdf

Human perception of 3D space has been investigated extensively, but there are conflicting reports regarding its distortions. A possible solution to these discrepancies is that 3D perception is in fact comprised of two different processes-perception of traveled space, and perception of surrounding space. Here we tested these two aspects on the same subjects, for the first time. To differentiate these two aspects and investigate whether they emerge from different processes, we asked whether these two aspects are affected differently by the individual's experience of 3D locomotion. Using an immersive high-grade flight-simulator with realistic virtual-reality, we compared these two aspects of 3D perception in fighter pilots-individuals highly experienced in 3D locomotion-and in control subjects. We found that the two aspects of 3D perception were affected differently by 3D locomotion experience: the perception of 3D traveled space was plastic and experience-dependent, differing dramatically between pilots and controls, while the perception of surrounding space was rigid and unaffected by experience. This dissociation suggests that these two aspects of 3D spatial perception emerge from two distinct processes.

Are grid cells used for navigation?: On local metrics, subjective spaces, and black holes

Ginosar G., Aljadeff J., Las L., Derdikman D. & Ulanovsky N. (2023) Neuron 111, 1858-1875

Ginosar2023a.pdf

The symmetric, lattice-like spatial pattern of grid-cell activity is thought to provide a neuronal global metric for space. This view is compatible with grid cells recorded in empty boxes but inconsistent with data from more naturalistic settings. We review evidence arguing against the global-metric notion, including the distortion and disintegration of the grid pattern in complex and three-dimensional environments. We argue that deviations from lattice symmetry are key for understanding grid-cell function. We propose three possible functions for grid cells, which treat real-world grid distortions as a feature rather than a bug. First, grid cells may constitute a local metric for proximal space rather than a global metric for all space. Second, grid cells could form a metric for subjective action-relevant space rather than physical space. Third, distortions may represent salient locations. Finally, we discuss mechanisms that can underlie these functions. These ideas may transform our thinking about grid cells.

Contextual and pure time coding for self and other in the hippocampus

Omer D. B., Las L. & Ulanovsky N. (2023) Nature Neuroscience 26, 285-294

Omer2023.pdf

Navigation and episodic memory depend critically on representing temporal sequences. Hippocampal 'time cells' form temporal sequences, but it is unknown whether they represent context-dependent experience or time per se. Here we report on time cells in bat hippocampal area CA1, which, surprisingly, formed two distinct populations. One population of time cells generated different temporal sequences when the bat hung at different locations, thus conjunctively encoding spatial context and time-'contextual time cells'. A second population exhibited similar preferred times across different spatial contexts, thus purely encoding elapsed time. When examining neural responses after the landing moment of another bat, in a social imitation task, we found time cells that encoded temporal sequences aligned to the other's landing. We propose that these diverse time codes may support the perception of interval timing, episodic memory and temporal coordination between self and others.

Spatial coding in the hippocampus and hyperpallium of flying owls

Agarwal A., Sarel A., Derdikman D., Ulanovsky N. & Gutfreund Y. (2023) PNAS 120, e2212418120

Agarwal2023.pdf

The elucidation of spatial coding in the hippocampus requires exploring diverse animal species. While robust place-cells are found in the mammalian hippocampus, much less is known about spatial coding in the hippocampus of birds. Here we used a wireless-electrophysiology system to record single neurons in the hippocampus and other two dorsal pallial structures from freely flying barn owls (Tyto alba), a central-place nocturnal predator species with excellent navigational abilities. The owls 3D position was monitored while it flew between perches. We found place cellsneurons that fired when the owl flew through a spatially restricted region in at least one directionas well as neurons that encoded the direction of flight, and neurons that represented the owls perching position between flights. Many neurons encoded combinations of position, direction, and perching. Spatial coding was maintained stable and invariant to lighting conditions. Place cells were observed in owls performing two different types of flying tasks, highlighting the generality of the result. Place coding was found in the anterior hippocampus and in the posterior part of the hyperpallium apicale, and to a lesser extent in the visual Wulst. The finding of place-cells in flying owls suggests commonalities in spatial coding across mammals and birds.

2022

Natural switches in behaviour rapidly modulate hippocampal coding

Sarel A., Palgi S., Blum D., Aljadeff J., Las L. & Ulanovsky N. (2022) Nature 609, 119-127

Sarel2022.pdf

Throughout their daily lives, animals and humans often switch between different behaviours. However, neuroscience research typically studies the brain while the animal is performing one behavioural task at a time, and little is known about how brain circuits represent switches between different behaviours. Here we tested this question using an ethological setting: two bats flew together in a long 135 m tunnel, and switched between navigation when flying alone (solo) and collision avoidance as they flew past each other (cross-over). Bats increased their echolocation click rate before each cross-over, indicating attention to the other bat(1-9). Hippocampal CA1 neurons represented the bat's own position when flying alone (place coding(10-14)). Notably, during cross-overs, neurons switched rapidly to jointly represent the interbat distance by self-position. This neuronal switch was very fast-as fast as 100 ms-which could be revealed owing to the very rapid natural behavioural switch. The neuronal switch correlated with the attention signal, as indexed by echolocation. Interestingly, the different place fields of the same neuron often exhibited very different tuning to interbat distance, creating a complex non-separable coding of position by distance. Theoretical analysis showed that this complex representation yields more efficient coding. Overall, our results suggest that during dynamic natural behaviour, hippocampal neurons can rapidly switch their core computation to represent the relevant behavioural variables, supporting behavioural flexibility.

Stereotaxic Brain Atlas of the Egyptian Fruit Bat

Eilam-Altstädter R., Las L., Witter M. P. & Ulanovsky N. (2022) Elsevier - BOOK - see here

The Stereotaxic Brain Atlas of the Egyptian Fruit Bat provides the first stereotaxic atlas of the brain of the Egyptian fruit bat (Rousettus aegyptiacus), an emerging model in neuroscience. This atlas contains coronal brain sections stained with cresyl violet (Nissl), AChE, and Parvalbumin all stereotaxically calibrated. It will serve the needs of any neuroscientist who wishes to work with these bats allowing to precisely target specific brain areas for electrophysiology, optogenetics, pharmacology, and lesioning. More broadly, this atlas will be useful to all neuroscientists working with bats, as it delineates many brain regions that were not delineated so far in any bat species. Finally, this atlas will provide a useful resource for researchers interested in comparative neuroanatomy of the mammalian brain.

2021

Locally ordered representation of 3D space in the entorhinal cortex

Ginosar G., Aljadeff J., Burak Y., Sompolinsky H., Las L. & Ulanovsky N. (2021) Nature 596, 404-409

Ginosar2021.pdf

As animals navigate on a two-dimensional surface, neurons in the medial entorhinal cortex (MEC) known as grid cells are activated when the animal passes through multiple locations (firing fields) arranged in a hexagonal lattice that tiles the locomotion surface¹. However, although our world is three-dimensional, it is unclear how the MEC represents 3D space². Here we recorded from MEC cells in freely flying bats and identified several classes of spatial neurons, including 3D border cells, 3D head-direction cells, and neurons with multiple 3D firing fields. Many of these multifield neurons were 3D grid cells, whose neighbouring fields were separated by a characteristic distanceforming a local orderbut lacked any global lattice arrangement of the fields. Thus, whereas 2D grid cells form a global latticecharacterized by both local and global order3D grid cells exhibited only local order, creating a locally ordered metric for space. We modelled grid cells as emerging from pairwise interactions between fields, which yielded a hexagonal lattice in 2D and local order in 3D, thereby describing both 2D and 3D grid cells using one unifying model. Together, these data and model illuminate the fundamental differences and similarities between neural codes for 3D and 2D space in the mammalian brain.

Directional tuning in the hippocampal formation of birds

Ben-Yishay E., Krivoruchko K., Ron S., Ulanovsky N., Derdikman D. & Gutfreund Y. (2021) Current Biology 31, 2592-2602

Ben-Yishay2021.pdf

Birds strongly rely on spatial memory and navigation. Therefore, it is of utmost interest to reveal how space is represented in the avian brain. Here we used tetrodes to record neurons from the hippocampal formation of Japanese quails-a ground-dwelling species-while the quails roamed in an open-field arena. Whereas spatially modulated cells (place cells, grid cells, border cells) were generally not encountered, the firing rate of about 12% of the neurons was unimodally and significantly modulated by the head azimuth-i.e., these were head-direction cells (HD cells). Typically, HD cells were maximally active at one preferred direction and minimally at the opposite null direction, with preferred directions spanning all 360° across the population. The preferred direction was independent of the animal's position and speed and was stable during the recording session. The HD tuning was broader compared to that of HD cells in rodents, and most cells had non-zero baseline firing in all directions. However, similar to findings in rodents, the HD tuning usually rotated with the rotation of a salient visual cue in the arena. Thus, these findings support the existence of an allocentric HD representation in the quail hippocampal formation and provide the first demonstration of HD cells in birds.

Multiscale representation of very large environments in the hippocampus of flying bats

Eliav T., Maimon S. R., Aljadeff J., Tsodyks M., Ginosar G., Las L. & Ulanovsky N. (2021) Science 372, eabg4020

Eliav2021.pdf

Hippocampal place cells encode the animals location. Place cells were traditionally studied in small environments, and nothing is known about large ethologically relevant spatial scales. We wirelessly recorded from hippocampal dorsal CA1 neurons of wild-born bats flying in a long tunnel (200 meters). The size of place fields ranged from 0.6 to 32 meters. Individual place cells exhibited multiple fields and a multiscale representation: Place fields of the same neuron differed up to 20-fold in size. This multiscale coding was observed from the first day of exposure to the environment, and also in laboratory-born bats that never experienced large environments. Theoretical decoding analysis showed that the multiscale code allows representation of very large environments with much higher precision than that of other codes. Together, by increasing the spatial scale, we discovered a neural code that is radically different from classical place codes.

2018

Nonoscillatory Phase Coding and Synchronization in the Bat Hippocampal Formation

Eliav T., Geva-Sagiv M., Yartsev M. M., Finkelstein A., Rubin A., Las L. & Ulanovsky N. (2018) Cell 175, 1119-1130

Eliav2018.pdf

Hippocampal theta oscillations were proposed to be important for multiple functions, including memory and temporal coding of position. However, previous findings from bats have questioned these proposals by reporting absence of theta rhythmicity in bat hippocampal formation. Does this mean that temporal coding is unique to rodent hippocampus and does not generalize to other species? Here, we report that, surprisingly, bat hippocampal neurons do exhibit temporal coding similar to rodents, albeit without any continuous oscillations at the 1-20 Hz range. Bat neurons exhibited very strong locking to the non-rhythmic fluctuations of the field potential, such that neurons were synchronized together despite the absence of oscillations. Further, some neurons exhibited "phase precession'' and phase coding of the bat's position-with spike phases shifting earlier as the animal moved through the place field. This demonstrates an unexpected type of neural coding in the mammalian brain-nonoscillatory phase coding-and highlights the importance of synchrony and temporal coding for hippocampal function across species.

Optimal dynamic coding by mixed-dimensionality neurons in the head-direction system of bats

Finkelstein A., Ulanovsky N., Tsodyks M. & Aljadeff J. (2018) Nature Communications 9, 3590

Finkelstein2018.pdf

Ethologically relevant stimuli are often multidimensional. In many brain systems, neurons with "pure" tuning to one stimulus dimension are found along with "conjunctive" neurons that encode several dimensions, forming an apparently redundant representation. Here we show using theoretical analysis that a mixed-dimensionality code can efficiently represent a stimulus in different behavioral regimes: encoding by conjunctive cells is more robust when the stimulus changes quickly, whereas on long timescales pure cells represent the stimulus more efficiently with fewer neurons. We tested our predictions experimentally in the bat head-direction system and found that many head-direction cells switched their tuning dynamically from pure to conjunctive representation as a function of angular velocity-confirming our theoretical prediction. More broadly, our results suggest that optimal dimensionality depends on population size and on the time available for decoding-which might explain why mixed-dimensionality representations are common in sensory, motor, and higher cognitive systems across species.

Social place-cells in the bat hippocampus

Omer D. B., Maimon S. R., Las L. & Ulanovsky N. (2018) Science 359, 218-224

Omer2018.pdf

Social animals have to know the spatial positions of conspecifics. However, it is unknown how the position of others is represented in the brain. We designed a spatial observational-learning task, in which an observer bat mimicked a demonstrator bat while we recorded hippocampal dorsal-CA1 neurons from the observer bat. A neuronal subpopulation represented the position of the other bat, in allocentric coordinates. About half of these "social placecells" represented also the observer's own position-that is, were place cells. The representation of the demonstrator bat did not reflect self-movement or trajectory planning by the observer. Some neurons represented also the position of inanimate moving objects; however, their representation differed from the representation of the demonstrator bat. This suggests a role for hippocampal CA1 neurons in social-spatial cognition.

2017

Vectorial representation of spatial goals in the hippocampus of bats

Sarel A., Finkelstein A., Las L. & Ulanovsky N. (2017) Science 355, 176-180

Sarel2017.pdf

To navigate, animals need to represent not only their own position and orientation, but also the location of their goal. Neural representations of an animal's own position and orientation have been extensively studied. However, it is unknown how navigational goals are encoded in the brain.We recorded from hippocampal CA1 neurons of bats flying in complex trajectories toward a spatial goal.We discovered a subpopulation of neurons with angular tuning to the goal direction. Many of these neurons were tuned to an occluded goal, suggesting that goal-direction representation is memory-based. We also found cells that encoded the distance to the goal, often in conjunction with goal direction. The goaldirection and goal-distance signals make up a vectorial representation of spatial goals, suggesting a previously unrecognized neuronal mechanism for goal-directed navigation.

Bat Navigation

Yovel Y. & Ulanovsky N. (2017) In: Learning and Memory: A Comprehensive Reference, second ed. (Academic Press). pp. 333-345

Yovel2017.pdf

Bats exhibit remarkable navigation capabilities on a wide range of spatial scales. In this chapter we summarize the current knowledge on bat navigation outdoors. We review previous research examining bats' use of different navigation strategies, including (1) beaconing, (2) route-following, (3) path integration, and (4) mental map. We then discuss what is known about the encoding of three-dimensional space in the bat's brain and its possible links to navigation. Finally, we highlight key open questions-at both the behavioral and neural levels-which should be pursued in future experiments to elucidate bat navigation and its neural mechanisms.

2016

The Representation of Prediction Error in Auditory Cortex

Rubin J., Ulanovsky N., Nelken I. & Tishby N. (2016) PLoS Computational Biology 12, e1005058

Rubin2016.pdf

To survive, organisms must extract information from the past that is relevant for their future. How this process is expressed at the neural level remains unclear. We address this problem by developing a novel approach from first principles. We show here how to generate low-complexity representations of the past that produce optimal predictions of future events. We then illustrate this framework by studying the coding of oddball sequences in auditory cortex. We find that for many neurons in primary auditory cortex, trial-by-trial fluctuations of neuronal responses correlate with the theoretical prediction error calculated from the short-term past of the stimulation sequence, under constraints on the complexity of the representation of this past sequence. In some neurons, the effect of prediction error accounted for more than 50% of response variability. Reliable predictions often depended on a representation of the sequence of the last ten or more stimuli, although the representation kept only few details of that sequence.

Hippocampal global remapping for different sensory modalities in flying bats

Geva-Sagiv M., Romani S., Las L. & Ulanovsky N. (2016) Nature Neuroscience 19, 952-958

GevaSagiv2016.pdf

Hippocampal place cells encode the animal's spatial position. However, it is unknown how different long-range sensory systems affect spatial representations. Here we alternated usage of vision and echolocation in Egyptian fruit bats while recording from single neurons in hippocampal areas CA1 and subiculum. Bats flew back and forth along a linear flight track, employing echolocation in darkness or vision in light. Hippocampal representations remapped between vision and echolocation via two kinds of remapping: subiculum neurons turned on or off, while CA1 neurons shifted their place fields. Interneurons also exhibited strong remapping. Finally, hippocampal place fields were sharper under vision than echolocation, matching the superior sensory resolution of vision over echolocation. Simulating several theoretical models of place-cells suggested that combining sensory information and path integration best explains the experimental sharpening data. In summary, here we show sensory-based global remapping in a mammal, suggesting that the hippocampus does not contain an abstract spatial map but rather a 'cognitive atlas', with multiple maps for different sensory modalities.

Brain Exploration, Off the Beaten Path

Kvajo M., Leonardo A., Ulanovsky N. & Laurent G. (2016) Cell 166, 525-527

Kvajo2016.pdf

Model organisms, such as rodents, monkeys, or Drosophila, have driven much of recent research in neuroscience. However, studies in other, more unusual systems have broadened the types of questions that are being asked and have revealed the diverse ways in which species tackle common problems. Cell editor Mirna Kvajo talked with Nachum Ulanovsky, Gilles Laurent, and Anthony Leonardo about their research and how studying bats, reptiles, and dragonflies informs big questions in neuroscience. An annotated excerpt of the conversation appears below, and the full conversation is available with the article online.

Whisking, Sniffing, and the Hippocampal θ-Rhythm: A Tale of Two Oscillators

Kleinfeld D., Deschênes M. & Ulanovsky N. (2016) PLoS Biology 14, e1002385

Kleinfeld2016.pdf

The hippocampus has unique access to neuronal activity across all of the neocortex. Yet an unanswered question is how the transfer of information between these structures is gated. One hypothesis involves temporal-locking of activity in the neocortex with that in the hippocampus. New data from the Matthew E. Diamond laboratory shows that the rhythmic neuronal activity that accompanies vibrissa-based sensation, in rats, transiently locks to ongoing hippocampal θ-rhythmic activity during the sensory-gathering epoch of a discrimination task. This result complements past studies on the locking of sniffing and the θ-rhythm as well as the relation of sniffing and whisking. An overarching possibility is that the preBötzinger inspiration oscillator, which paces whisking, can selectively lock with the θ-rhythm to traffic sensorimotor information between the rats neocortex and hippocampus.

3-D Maps and Compasses in the Brain

Finkelstein A., Las L. & Ulanovsky N. (2016) Annual Review of Neuroscience 39, 171-196

Finkelstein2016.pdf

The world has a complex, three-dimensional (3-D) spatial structure, but until recently the neural representation of space was studied primarily in planar horizontal environments. Here we review the emerging literature on allocentric spatial representations in 3-D and discuss the relations between 3-D spatial perception and the underlying neural codes. We suggest that the statistics of movements through space determine the topology and the dimensionality of the neural representation, across species and different behavioral modes. We argue that hippocampal place-cell maps are metric in all three dimensions, and might be composed of 2-D and 3-D fragments that are stitched together into a global 3-D metric representation via the 3-D head-direction cells. Finally, we propose that the hippocampal formation might implement a neural analogue of a Kalman filter, a standard engineering algorithm used for 3-D navigation.

2015

Three-dimensional head-direction coding in the bat brain

Finkelstein A., Derdikman D., Rubin A., Foerster J. N., Las L. & Ulanovsky N. (2015) Nature 517, 159-164

Finkelstein2015.pdf

Navigation requires a sense of direction (compass), which in mammals is thought to be provided by head-direction cells, neurons that discharge when the animals head points to a specific azimuth. However, it remains unclear whether a three-dimensional (3D) compass exists in the brain. Here we conducted neural recordings in bats, mammals well-adapted to 3D spatial behaviours, and found head-direction cells tuned to azimuth, pitch or roll, or to conjunctive combinations of 3D angles, in both crawling and flying bats. Head-direction cells were organized along a functionalanatomical gradient in the presubiculum, transitioning from 2D to 3D representations. In inverted bats, the azimuth-tuning of neurons shifted by 180°, suggesting that 3D head direction is represented in azimuth × pitch toroidal coordinates. Consistent with our toroidal model, pitch-cell tuning was unimodal, circular, and continuous within the available 360° of pitch. Taken together, these results demonstrate a 3D head-direction mechanism in mammals, which could support navigation in 3D space.

Spatial cognition in bats and rats: From sensory acquisition to multiscale maps and navigation

Geva-Sagiv M., Las L., Yovel Y. & Ulanovsky N. (2015) Nature Reviews Neuroscience 16, 94-108

GevaSagiv2015.pdf

Spatial orientation and navigation rely on the acquisition of several types of sensory information. This information is then transformed into a neural code for space in the hippocampal formation through the activity of place cells, grid cells and head-direction cells. These spatial representations, in turn, are thought to guide long-range navigation. But how the representations encoded by these different cell types are integrated in the brain to form a neural 'map and compass' is largely unknown. Here, we discuss this problem in the context of spatial navigation by bats and rats. We review the experimental findings and theoretical models that provide insight into the mechanisms that link sensory systems to spatial representations and to large-scale natural navigation.

A Sensory-Motor Control Model of Animal Flight Explains Why Bats Fly Differently in Light Versus Dark

Bar N. S., Skogestad S., Marcal J. M., Ulanovsky N. & Yovel Y. (2015) PLoS Biology 13, e1002046

Bar2015.pdf

Animal flight requires fine motor control. However, it is unknown how flying animals rapidly transform noisy sensory information into adequate motor commands. Here we developed a sensorimotor control model that explains vertebrate flight guidance with high fidelity. This simple model accurately reconstructed complex trajectories of bats flying in the dark. The model implies that in order to apply appropriate motor commands, bats have to estimate not only the angle-to-target, as was previously assumed, but also the angular velocity (\u201cproportional-derivative\u201d controller). Next, we conducted experiments in which bats flew in light conditions. When using vision, bats altered their movements, reducing the flight curvature. This change was explained by the model via reduction in sensory noise under vision versus pure echolocation. These results imply a surprising link between sensory noise and movement dynamics. We propose that this sensory-motor link is fundamental to motion control in rapidly moving animals under different sensory conditions, on land, sea, or air.

2014

Editorial overview: Neural maps

Fitzpatrick D. & Ulanovsky N. (2014) Current Opinion in Neurobiology 24, iv-vi

Fitzpatrick2014.pdf

Hippocampal neurophysiology across species

Las L. & Ulanovsky N. (2014) In: Space, Time and Memory in the Hippocampal Formation (Springer), pp. 431-461

Las2014.pdf

Comparative research in neuroscience can contribute to the understanding of general principles underlying brain function; it can also provide testable hypotheses that direct future research. This chapter provides a comparative review of the neurophysiology of the hippocampal formation across mammals. Over the last 40 years, the vast majority of findings on hippocampal electrophysiology were based on research from a single animal model-the rat. Yet, while rat hippocampal studies provided one of the richest datasets in systems neuroscience, the paradigms generated based on rat data were, until recently, largely untested in other mammals-and at least some of the ideas have been questioned by the few studies that were conducted in other species. Here we will summarize the data available from different mammalian species regarding hippocampal neurophysiology, focusing on similarities and differences across species-including functional implications. We will limit our discussion to two aspects: spatial cell types in the hippocampal formation and hippocampal oscillations. We will conclude by highlighting some of the major gaps in the available comparative data and by raising a call to arms to conduct further comparative research on the hippocampal formation.

Encoding of head direction by hippocampal place cells in bats

Rubin A., Yartsev M. M. & Ulanovsky N. (2014) Journal of Neuroscience 34, 1067-1080

Rubin2014.pdf

Most theories of navigation rely on the concept of a mental map and compass. Hippocampal place cells are neurons thought to be important for representing the mental map; these neurons become active when the animal traverses a specific location in the environment (the "place field"). Head-direction cells are found outside the hippocampus, and encode the animal's head orientation, thus implementing a neural compass. The prevailing view is that the activity of head-direction cells is not tuned to a single place, while place cells do not encode head direction. However, little work has been done to investigate in detail the possible head-directional tuning of hippocampal place cells across species. Here we addressed this by recording the activity of single neurons in the hippocampus of two evolutionarily distant bat species, Egyptian fruit bat and big brown bat, which crawled randomly in three different open-field arenas. We found that a large fraction of hippocampal neurons, in both bat species, showed conjunctive sensitivity to the animal's spatial position (place field) and to its head direction. We introduced analytical methods to demonstrate that the head-direction tuning was significant even after controlling for the behavioral coupling between position and head direction. Surprisingly, some hippocampal neurons preserved their head direction tuning even outside the neuron's place field, suggesting that "spontaneous" extra-field spikes are not noise, but in fact carry head-direction information. Overall, these findings suggest that bat hippocampal neurons can convey both map information and compass information.

2013

Representation of three-dimensional space in the hippocampus of flying bats

Yartsev M. M. & Ulanovsky N. (2013) Science 340, 367-372

Yartsev2013.pdf

Many animals, on air, water, or land, navigate in three-dimensional (3D) environments, yet it remains unclear how brain circuits encode the animal's 3D position. We recorded single neurons in freely flying bats, using a wireless neural-telemetry system, and studied how hippocampal place cells encode 3D volumetric space during flight. Individual place cells were active in confined 3D volumes, and in >90% of the neurons, all three axes were encoded with similar resolution. The 3D place fields from different neurons spanned different locations and collectively represented uniformly the available space in the room. Theta rhythmicity was absent in the firing patterns of 3D place cells. These results suggest that the bat hippocampus represents 3D volumetric space by a uniform and nearly isotropic rate code.

2011

Neuroscience: How is three-dimensional space encoded in the brain?

Ulanovsky N. (2011) Current Biology 21, R886-888

Ulanovsky2011.pdf

Grid cells without theta oscillations in the entorhinal cortex of bats

Yartsev M. M., Witter M. P. & Ulanovsky N. (2011) Nature 479, 103-107

Yartsev2011.pdf

Grid cells provide a neural representation of space, by discharging when an animal traverses through the vertices of a periodic hexagonal grid spanning the environment. Although grid cells have been characterized in detail in rats, the fundamental question of what neural dynamics give rise to the grid structure remains unresolved. Two competing classes of models were proposed: network models, based on attractor dynamics, and oscillatory interference models, which propose that interference between somatic and dendritic theta-band oscillations (4-10ĝ\u20acHz) in single neurons transforms a temporal oscillation into a spatially periodic grid. So far, these models could not be dissociated experimentally, because rodent grid cells always co-exist with continuous theta oscillations. Here we used a novel animal model, the Egyptian fruit bat, to refute the proposed causal link between grids and theta oscillations. On the basis of our previous finding from bat hippocampus, of spatially tuned place cells in the absence of continuous theta oscillations, we hypothesized that grid cells in bat medial entorhinal cortex might also exist without theta oscillations. Indeed, we found grid cells in bat medial entorhinal cortex that shared remarkable similarities to rodent grid cells. Notably, the grids existed in the absence of continuous theta-band oscillations, and with almost no theta modulation of grid-cell spiking-both of which are essential prerequisites of the oscillatory interference models. Our results provide a direct demonstration of grid cells in a non-rodent species. Furthermore, they strongly argue against a major class of computational models of grid cells.

Active control of acoustic field-of-view in a biosonar system

Yovel Y., Falk B., Moss C. F. & Ulanovsky N. (2011) PLoS Biology 9, e1001150

Yovel2011.pdf

Active-sensing systems abound in nature, but little is known about systematic strategies that are used by these systems to scan the environment. Here, we addressed this question by studying echolocating bats, animals that have the ability to point their biosonar beam to a confined region of space. We trained Egyptian fruit bats to land on a target, under conditions of varying levels of environmental complexity, and measured their echolocation and flight behavior. The bats modulated the intensity of their biosonar emissions, and the spatial region they sampled, in a task-dependant manner. We report here that Egyptian fruit bats selectively change the emission intensity and the angle between the beam axes of sequentially emitted clicks, according to the distance to the target, and depending on the level of environmental complexity. In so doing, they effectively adjusted the spatial sector sampled by a pair of clicks-the "field-of-view." We suggest that the exact point within the beam that is directed towards an object (e.g., the beam's peak, maximal slope, etc.) is influenced by three competing task demands: detection, localization, and angular scanning-where the third factor is modulated by field-of-view. Our results suggest that lingual echolocation (based on tongue clicks) is in fact much more sophisticated than previously believed. They also reveal a new parameter under active control in animal sonar-the angle between consecutive beams. Our findings suggest that acoustic scanning of space by mammals is highly flexible and modulated much more selectively than previously recognized.

Large-scale navigational map in a mammal

Tsoar A., Nathan R., Bartan Y., Vyssotski A., Dell'Omo G. & Ulanovsky N. (2011) PNAS 108, E718-724

Tsoar2011.pdf

Navigation, the ability to reach desired goal locations, is critical for animals and humans. Animal navigation has been studied extensively in birds, insects, and some marine vertebrates and invertebrates, yet we are still far from elucidating the underlying mechanisms in other taxonomic groups, especially mammals. Here we report a systematic study of the mechanisms of long-range mammalian navigation. High-resolution global positioning system tracking of bats was conducted here, which revealed high, fast, and very straight commuting flights of Egyptian fruit bats (Rousettus aegyptiacus) from their cave to remote fruit trees. Bats returned to the same individual trees night after night. When displaced 44 km south, bats homed directly to one of two goal locations-familiar fruit tree or cave-ruling out beaconing, route-following, or path-integration mechanisms. Bats released 84 km south, within a deep natural crater, were initially disoriented (but eventually left the crater toward the home direction and homed successfully), whereas bats released at the crater-edge top homed directly, suggesting navigation guided primarily by distal visual landmarks. Taken together, these results provide evidence for a large-scale "cognitive map" that enables navigation of a mammal within its visually familiar area, and they also demonstrate the ability to home back when translocated outside the visually familiar area.

Click-based echolocation in bats: Not so primitive after all

Yovel Y., Geva-Sagiv M. & Ulanovsky N. (2011) Journal of Comparative Physiology A 197, 515-530

Yovel2011b.pdf

Echolocating bats of the genus Rousettus produce click sonar signals, using their tongue (lingual echolocation). These signals are often considered rudimentary and are believed to enable only crude performance. However, the main argument supporting this belief, namely the click's reported long duration, was recently shown to be an artifact. In fact, the sonar clicks of Rousettus bats are extremely short, ~50-100 μs, similar to dolphin vocalizations. Here, we present a comparison between the sonar systems of the 'model species' of laryngeal echolocation, the big brown bat (Eptesicus fuscus), and that of lingual echolocation, the Egyptian fruit bat (Rousettus aegyptiacus). We show experimentally that in tasks, such as accurate landing or detection of medium-sized objects, click-based echolocation enables performance similar to laryngeal echolocators. Further, we describe a sophisticated behavioral strategy for biosonar beam steering in clicking bats. Finally, theoretical analyses of the signal design-focusing on their autocorrelations and wideband ambiguity functions-predict that in some aspects, such as target ranging and Doppler-tolerance, click-based echolocation might outperform laryngeal echolocation. Therefore, we suggest that click-based echolocation in bats should be regarded as a viable echolocation strategy, which is in fact similar to the biosonar used by most echolocating animals, including whales and dolphins.

Dynamics of hippocampal spatial representation in echolocating bats

Ulanovsky N. & Moss C. F. (2011) Hippocampus 21, 150-161

Ulanovsky2011b.pdf

The "place fields" of hippocampal pyramidal neurons are not static. For example, upon a contextual change in the environment, place fields may "remap" within typical timescales of ∼1 min. A few studies have shown more rapid dynamics in hippocampal activity, linked to internal processes, such as switches between spatial reference frames or changes within the theta cycle. However, little is known about rapid hippocampal place field dynamics in response to external, sensory stimuli. Here, we studied this question in big brown bats, echolocating mammals in which we can readily measure rapid changes in sensory dynamics (sonar signals), as well as rapid behavioral switches between distal and proximal exploratory modes. First, we show that place field size was modulated by the availability of sensory information, on a timescale of ∼300 ms: Bat hippocampal place fields were smallest immediately after an echolocation call, but place fields "diffused" with the passage of time after the call, when echo information was no longer arriving. Second, we show rapid modulation of hippocampal place fields as the animal switched between two exploratory modes. Third, we compared place fields and spatial view fields of individual neurons and found that place tuning was much more pronounced than spatial view tuning. In addition, dynamic fluctuations in spatial view tuning were stronger than fluctuations in place tuning. Taken together, these results suggest that spatial representation in mammalian hippocampus can be very rapidly modulated by external sensory and behavioral events.

2010

Optimal localization by pointing off axis

Yovel Y., Falk B., Moss C. F. & Ulanovsky N. (2010) Science 327, 701-704

Yovel2010.pdf

Is centering a stimulus in the field of view an optimal strategy to localize and track it? We demonstrated, through experimental and computational studies, that the answer is no. We trained echolocating Egyptian fruit bats to localize a target in complete darkness, and we measured the directional aim of their sonar clicks. The bats did not center the sonar beam on the target, but instead pointed it off axis, accurately directing the maximum slope ("edge") of the beam onto the target. Information-theoretic calculations showed that using the maximum slope is optimal for localizing the target, at the cost of detection. We propose that the tradeoff between detection (optimized at stimulus peak) and localization (optimized at maximum slope) is fundamental to spatial localization and tracking accomplished through hearing, olfaction, and vision.

2008

What the bat's voice tells the bat's brain

Ulanovsky N. & Moss C. F. (2008) PNAS 105, 8491-8498

Ulanovsky2008.pdf

For over half a century, the echolocating bat has served as a valuable model in neuroscience to elucidate mechanisms of auditory processing and adaptive behavior in biological sonar. Our article emphasizes the importance of the bat's vocal-motor system to spatial orientation by sonar, and we present this view in the context of three problems that the echolocating bat must solve: (i) auditory scene analysis, (ii) sensorimotor transformations, and (iii) spatial memory and navigation. We summarize our research findings from behavioral studies of echolocating bats engaged in natural tasks and from neurophysiological studies of the bat superior colliculus and hippocampus, brain structures implicated in sensorimotor integration, orientation, and spatial memory. Our perspective is that studies of neural activity in freely vocalizing bats engaged in natural behaviors will prove essential to advancing a deeper understanding of the mechanisms underlying perception and memory in mammals.

2007

Rapid jamming avoidance in biosonar

Gillam E. H., Ulanovsky N. & McCracken G. F. (2007) Proceedings of the Royal Society B 274, 651-660

Gillam2007.pdf

The sonar systems of bats and dolphins are in many ways superior to man-made sonar and radar systems, and considerable effort has been devoted to understanding the signal-processing strategies underlying these capabilities. A major feature determining the efficiency of sonar systems is the sensitivity to noise and jamming signals. Previous studies indicated that echolocating bats may adjust their signal structure to avoid jamming ('jamming avoidance response'; JAR). However, these studies relied on behavioural correlations and not controlled experiments. Here, we provide the first experimental evidence for JAR in bats. We presented bats (Tadarida brasiliensis) with 'playback stimuli' consisting of recorded echolocation calls at one of six frequencies. The bats exhibited a JAR by shifting their call frequency away from the presented playback frequency. When the approaching bats were challenged by an abrupt change in the playback stimulus, they responded by shifting their call frequencies upwards, away from the playback. Interestingly, even bats initially calling below the playback's frequency shifted their frequencies upwards, 'jumping' over the playback frequency. These spectral shifts in the bats' calls occurred often within less than 200 ms, in the first echolocation call emitted after the stimulus switch - suggesting that rapid jamming avoidance is important for the bat.

Hippocampal cellular and network activity in freely moving echolocating bats

Ulanovsky N. & Moss C. F. (2007) Nature Neuroscience 10, 224-233

Ulanovsky2007.pdf

The hippocampus is crucial for episodic and spatial memory. In freely moving rodents, hippocampal pyramidal neurons show spatially selective firing when the animal passes through a neuron's 'place-field', and theta-band oscillation is continuously present during locomotion. Here we report the first hippocampal recordings from echolocating bats, mammals phylogenetically distant from rodents, which showed place cells very similar to those of rodents. High-frequency 'ripple' oscillations were also rodent-like. Theta oscillation, however, differed from rodents in two important ways: (i) theta occurred when bats explored the environment without locomoting, using distal sensing through echolocation, and (ii) theta was not continuous, but occurred in short intermittent bouts. The intermittence of theta suggests that models of hippocampal function that rely on continuous theta may not apply to bats. Our data support the hypothesis that theta oscillation in the mammalian hippocampus is involved in sequence learning and hence, theta power should increase with sensory-input rate - which explains why theta power correlates with running speed in rodents and with echolocation call rate in bats.

Mismatch negativity and stimulus-specific adaptation in animal models

Nelken I. & Ulanovsky N. (2007) Journal of Psychophysiology 21, 214-223

Nelken2007.pdf

Animal models of MMN may serve both to further our understanding of neural processing beyond pure sensory coding and for unraveling the neural and pharmacological processes involved in the generation of MMN. We start this review by discussing the methodological issues that are especially important when pursuing a single-neuron correlate of MMN. Correlates of MMN have been studied in mice, rats, cats, and primates. Whereas essentially all of these studies demonstrated the presence of stimulus-specific adaptation, in the sense that responses to deviant tones are larger than the responses to standard tones, the presence of real MMN has been established only in a few. We argue for the use of more and better controls in order to clarify the situation. Finally, we discuss in detail the relationships between stimulus-specific adaptation of single-neuron responses, as established in the cat auditory cortex, and MMN. We argue that this is currently the only fully established correlate of true change detection, and hypothesize that it precedes and probably induces the neural activity that is eventually measured as MMN.

2004

Multiple time scales of adaptation in auditory cortex neurons

Ulanovsky N., Las L., Farkas D. & Nelken I. (2004) Journal of Neuroscience 24, 10440-10453

Ulanovsky2004a.pdf

Neurons in primary auditory cortex (A1) of cats show strong stimulus-specific adaptation (SSA). In probabilistic settings, in which one stimulus is common and another is rare, responses to common sounds adapt more strongly than responses to rare sounds. This SSA could be a correlate of auditory sensory memory at the level of single A1 neurons. Here we studied adaptation in A1 neurons, using three different probabilistic designs. We showed that SSA has several time scales concurrently, spanning many orders of magnitude, from hundreds of milliseconds to tens of seconds. Similar time scales are known for the auditory memory span of humans, as measured both psychophysically and using evoked potentials. A simple model, with linear dependence on both short-term and long-term stimulus history, provided a good fit to A1 responses. Auditory thalamus neurons did not show SSA, and their responses were poorly fitted by the same model. In addition, SSA increased the proportion of failures in the responses of A1 neurons to the adapting stimulus. Finally, SSA caused a bias in the neuronal responses to unbiased stimuli, enhancing the responses to eccentric stimuli. Therefore, we propose that a major function of SSA in A1 neurons is to encode auditory sensory memory on multiple time scales. This SSA might play a role in stream segregation and in binding of auditory objects over many time scales, a property that is crucial for processing of natural auditory scenes in cats and of speech and music in humans.

Dynamics of jamming avoidance in echolocating bats

Ulanovsky N., Fenton M. B., Tsoar A. & Korine C. (2004) Proceedings of the Royal Society B 271, 1467-1475

Ulanovsky2004b.pdf

Animals using active sensing systems such as echolocation or electrolocation may experience interference from the signals of neighbouring conspecifics, which can be offset by a jamming avoidance response (JAR). Here, we report JAR in one echolocating bat (Tadarida teniotis: Molossidae) but not in another (Taphozous perforatus: Emballonuridae) when both flew and foraged with conspecifics. In T. teniotis, JAR consisted of shifts in the dominant frequencies of echolocation calls, enhancing differences among individuals. Larger spectral overlap of signals elicited stronger JAR. Tadarida teniotis showed two types of JAR: (i) for distant conspecifics: a symmetric JAR, with lower- and higher-frequency bats shifting their frequencies downwards and upwards, respectively, on average by the same amount; and (ii) for closer conspecifics: an asymmetric JAR, with only the upper-frequency bat shifting its frequency upwards. In comparison, 'wave-type' weakly electric fishes also shift frequencies of discharges in a JAR, but unlike T. teniotis, the shifts are either symmetric in some species or asymmetric in others. We hypothesize that symmetric JAR in T. teniotis serves to avoid jamming and improve echolocation, whereas asymmetric JAR may aid communication by helping to identify and locate conspecifics, thus minimizing chances of mid-air collisions.

2003

Primary auditory cortex of cats: Feature detection or something else?

Nelken I., Fishbach A., Las L., Ulanovsky N. & Farkas D. (2003) Biological Cybernetics 89, 397-406

Nelken2003.pdf

Neurons in sensory cortices are often assumed to be "feature detectors", computing simple and then successively more complex features out of the incoming sensory stream. These features are somehow integrated into percepts. Despite many years of research, a convincing candidate for such a feature in primary auditory cortex has not been found. We argue that feature detection is actually a secondary issue in understanding standing the role of primary auditory cortex. Instead, the major contribution of primary auditory cortex to auditory perception is in processing previously derived features on a number of different timescales. We hypothesize that, as a result, neurons in primary auditory cortex represent sounds in terms of auditory objects rather than in terms of feature maps. According to this hypothesis, primary auditory cortex has a pivotal role in the auditory system in that it generates the representation of auditory objects to which higher auditory centers assign properties such as spatial location, source identity, and meaning.

Processing of low-probability sounds by cortical neurons

Ulanovsky N., Las L. & Nelken I. (2003) Nature Neuroscience 6, 391-398

Ulanovsky2003.pdf

The ability to detect rare auditory events can be critical for survival. We report here that neurons in cat primary auditory cortex (A1) responded more strongly to a rarely presented sound than to the same sound when it was common. For the rare stimuli, we used both frequency and amplitude deviants. Moreover, some A1 neurons showed hyperacuity for frequency deviants - a frequency resolution one order of magnitude better than receptive field widths in A1. In contrast, auditory thalamic neurons were insensitive to the probability of frequency deviants. These phenomena resulted from stimulus-specific adaptation in A1, which may be a single-neuron correlate of an extensively studied cortical potential - mismatch negativity - that is evoked by rare sounds. Our results thus indicate that A1 neurons, in addition to processing the acoustic features of sounds, may also be involved in sensory memory and novelty detection.