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R U Muller

Publications and source records attributed to R U Muller.

At least 37 records · Page 2Linked to original sources
PubMed1996

Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus.

To relate different forms of synaptic plasticity to the formation and maintenance of place cells in the hippocampus, we have recorded place cells in freely behaving, transgenic mice that express a mutated Ca2+-independent form of CaM Kinase II. These mice have normal long-term potentiation (LTP) at 100 Hz, but they lack LTP in response to stimulation at 5-10 Hz and are impaired on spatial memory tasks. In these transgenic mice, the place cells in the CA1 region have three important differences from those of wild types: they are less common, less precise, and less stable. These findings suggest that LTP in the 5-10 Hz range may be important for the maintenance of place-field stability and that this stability may be essential for the storage of spatial memory.

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PubMed1996

Hippocampal place cells connected by Hebbian synapses can solve spatial problems.

We propose that a cognitive map can be stored in the synapses between the pyramidal cells of CA3 in the form of the pattern of synaptic strengths connecting them. The model requires only that there are place cells in CA3 and that the connections between them are modifiable in a Hebbian manner. Given these suppositions, the synaptic strengths must evolve to represent the distance between firing centers of synaptically connected place cells. We argue that this arrangement of synaptic weights embodies all the formal properties of a map. We demonstrate that the information stored in such a structure is sufficient to solve several classic spatial problems including finding shortest paths, and negotiating detours. It is clear that much of the physiology and anatomy necessary to more precisely characterize the model is not known at this time. Nevertheless the model is robust under a variety of cell and connection densities. It also performs well under several different functions relating distance to synaptic strength. What is most remarkable in the model is that it is a logical consequence of the several key anatomical and physiological properties of the CA3 region of rats. Whether this information is used by the rat is difficult to assess at this time. Regardless of the outcome of this question, the model has promising applications to the field of robot navigation.

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PubMed1996

Head direction cells: properties and functional significance.

The strong signal carried by head direction cells in the postsubiculum complements the positional signal carried by hippocampal place cells; together, the directional and positional signals provide the information necessary to permit rats to generate and carry out intelligent, efficient solutions to spatial problems. Our opinion is that the hippocampal positional system acts as a cognitive map and that the role of the directional system is to put the map into register with the environment. In this way, paths found using the map can be properly executed. Head direction cells have recently been discovered in parts of the thalamus reciprocally connected with the postsubiculum; such cells provide important clues to the organization of the directional system.

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PubMed1996

The hippocampus as a cognitive graph.

A theory of cognitive mapping is developed that depends only on accepted properties of hippocampal function, namely, long-term potentiation, the place cell phenomenon, and the associative or recurrent connections made among CA3 pyramidal cells. It is proposed that the distance between the firing fields of connected pairs of CA3 place cells is encoded as synaptic resistance (reciprocal synaptic strength). The encoding occurs because pairs of cells with coincident or overlapping fields will tend to fire together in time, thereby causing a decrease in synaptic resistance via long-term potentiation; in contrast, cells with widely separated fields will tend never to fire together, causing no change or perhaps (via long-term depression) an increase in synaptic resistance. A network whose connection pattern mimics that of CA3 and whose connection weights are proportional to synaptic resistance can be formally treated as a weighted, directed graph. In such a graph, a "node" is assigned to each CA3 cell and two nodes are connected by a "directed edge" if and only if the two corresponding cells are connected by a synapse. Weighted, directed graphs can be searched for an optimal path between any pair of nodes with standard algorithms. Here, we are interested in finding the path along which the sum of the synaptic resistances from one cell to another is minimal. Since each cell is a place cell, such a path also corresponds to a path in two-dimensional space. Our basic finding is that minimizing the sum of the synaptic resistances along a path in neural space yields the shortest (optimal) path in unobstructed two-dimensional space, so long as the connectivity of the network is great enough. In addition to being able to find geodesics in unobstructed space, the same network enables solutions to the "detour" and "shortcut" problems, in which it is necessary to find an optimal path around a newly introduced barrier and to take a shorter path through a hole opened up in a preexisting barrier, respectively. We argue that the ability to solve such problems qualifies the proposed hippocampal object as a cognitive map. Graph theory thus provides a sort of existence proof demonstrating that the hippocampus contains the necessary information to function as a map, in the sense postulated by others (O'Keefe, J., and L. Nadel. 1978. The Hippocampus as a Cognitive Map. Clarendon Press, Oxford, UK). It is also possible that the cognitive mapping functions of the hippocampus are carried out by parallel graph searching algorithms implemented as neural processes. This possibility has the great attraction that the hippocampus could then operate in much the same way to find paths in general problem space; it would only be necessary for pyramidal cells to exhibit a strong nonpositional firing correlate.

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PubMed1994

Place cells in the ventral hippocampus of rats.

Many cells recorded from the dorsal hippocampus of freely moving rats are intensely active only when the rat's head is in a particular part of its environment. For this reason, such units are called 'place cells'. We have investigated whether place cells are also found in the ventral hippocampus. Recordings were made from ventral hippocampal units while rats chased food pellets in a cylindrical arena. The rat's position was simultaneously recorded by tracking a light on the rat's head. Our data show the existence of cells in the ventral hippocampus whose positional firing patterns and electrophysiological properties are very similar to those of dorsal hippocampal place cells.

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PubMed1994

On the directional firing properties of hippocampal place cells.

Using a two-spot tracking system that allowed measurements of the direction of a rat's head in the environment as well as the position of the rat's head, we investigated whether hippocampal place cells show true direction-specific as well as location-specific firing. Significant modulations of firing rate by head direction were seen for most cells while rats chased food pellets in a cylindrical apparatus. It was possible, however, to account quantitatively for directional modulation with a simple scheme that we refer to as the "distributive hypothesis." This hypothesis assumes that firing is ideally location specific, and that all directional firing modulations are due to differences in the time that the rat spends in different portions of the firing field of the place cell in different head direction sectors. When the distributive hypothesis is put into numeric form, the directional firing profiles that it predicts are extremely similar to the observed directional firing profiles, strongly suggesting that there is no intrinsic directional specificity of place cell firing in the cylinder. Additional recordings made while rats ran on an eight-arm maze reveal that many firing fields on the arms are polarized; the cell discharges more rapidly when the rat runs in one direction than the other on the maze. This result provides an independent confirmation of the findings of McNaughton et al. (1983). For fields that appear to be polarized by inspecting firing rate maps of the raw data, the magnitude of directional firing variations is greater than predicted by the distributive hypothesis. By comparison with postsubicular head direction cells, it is shown that the distributive prediction of weaker-than-observed directional firing is expected if there is a true directional firing component. A major conclusion reached from recording in both environments is that the directional firing properties of hippocampal place cells are variable and not fixed; this is true of individual units as well as of the population.

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PubMed1992

The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells.

Hippocampal place cells in the rat are so named because they fire predominantly within circumscribed regions of the environment. This study describes the positional firing properties of cells afferent to hippocampal place cells, in superficial layers of medial entorhinal cortex (MEC). MEC cells in these layers project to the hippocampus via the perforant path and, along with lateral entorhinal cells, are the sole route by which cortical information reaches the hippocampus. MEC cells were recorded from rats while they retrieved pellets in simple geometric enclosures. The behavioral task as well as procedures for data collection and analysis were the same used in previous studies on hippocampal place cells (e.g., Muller et al., 1987) in order to facilitate the direct comparison between hippocampal and entorhinal cells. The firing patterns of MEC cells show pronounced locational variations reminiscent of hippocampal firing fields, but with a lower signal-to-noise ratio. While noisy, MEC firing patterns are stationary in time as evidenced by their reproducibility, and the improvement in spatial signal with long-duration recordings. Furthermore, MEC firing patterns are not due to variations in the rat's behavior. Taken together, these data show that the positional firing variations in MEC cells are due to the location-specificity of MEC cells. These and additional data lead us to conclude that location-specific information exists prior to the hippocampus. MEC cells are similar to hippocampal place cells in that their firing can be controlled by the rotation of a visual cue (a white card attached to the wall), but is not disrupted by removing the cue. An important difference between hippocampal and entorhinal cells was seen when the shape of the recording chamber was changed. In the transition from a cylinder to an equal-area square of similar appearance, MEC firing patterns topologically transformed (or "stretched") while those of hippocampal place cells changed to an unpredictable pattern. We conclude that the positional firing of MEC cells is more "sensory bound" than hippocampal cells, and that the ability to discriminate different environments, while present in the hippocampus, is not yet present in its input from MEC.

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PubMed1991

Experience-dependent modifications of hippocampal place cell firing.

Understanding the empirical rules that regulate alterations of hippocampal firing fields will enhance our understanding of hippocampal function. The current study sought to extend previous research in this area by examining the effect of substituting a new stimulus for a familiar stimulus in a familiar environment. Hippocampal place cells were recorded while rats chased food pellets scattered onto the floor of a cylindrical apparatus with a white cue card affixed to the apparatus wall. Once a place cell had been recorded in the presence of the white card, the white card was replaced by a black card of the same size and shape. The place cell was then recorded in the presence of the black card. Thirty-six cells were recorded using this procedure. All cells had stable firing fields in the presence of the white card. Both the white and black cards had stimulus control over place cell firing; generally, rotation of either card caused an equal rotation of the firing fields present. When the black card was substituted for the white card, place cells showed time-variant changes in their spatial firing patterns. The change was such that the spatial firing patterns of the majority of place cells were similar in the presence of the white and black cards during initial black card exposures. During subsequent presentations of the black card, the spatial firing patterns associated with the 2 cards became distinct from each other. Once the differentiation of firing patterns had occurred in a given rat, all place cells subsequently recorded from that rat had different firing patterns in the presence of the white and black cards. The findings are discussed relative to sensory-, motor-, attentional-, and learning-related interpretations of hippocampal function. It is argued that the time-variant alteration of place cell firing fields observed following exposure to a novel stimulus in this study reflects an experience-dependent modification of place cell firing patterns.

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PubMed1990

Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis.

This paper is a study of the behavioral and spatial firing correlates of neurons in the rat postsubiculum. Recordings were made from postsubicular neurons as rats moved freely throughout a cylindrical chamber, where the major cue for orientation was a white card taped to the inside wall. An automatic video/computer system monitored cell discharge while simultaneously tracking the position of 2 colored light emitting diodes (LEDs) secured to the animal's head. The animal's location was calculated from the position of one of the LEDs and head direction in the horizontal plane calculated from the relative positions of the 2 LEDs. Approximately 26% of the cells were classified as head-direction cells because they discharged as a function of the animal's head direction in the horizontal plane, independent of the animal's behavior, location, or trunk position. For each head-direction cell, vectors drawn in the direction of maximal firing were parallel throughout the recording chamber and did not converge toward a single point. Plots of firing rate versus head direction showed that each firing-rate/head-direction function was adequately described by a triangular function. Each cell's maximum firing rate occurred at only one (the preferred) head direction; firing rates at head directions on either side of the preferred direction decreased linearly with angular deviation from the preferred direction. Results from 24 head-direction cells in 7 animals showed an equal distribution of preferred firing directions over a 360 degrees angle. The peak firing rate of head-direction cells varied from 5 to 115 spikes/sec (mean: 35). The range of head-direction angles over which discharge was elevated (directional firing range) was usually about 90 degrees, with little, if any, discharge at head directions outside this range. Quantitative analysis showed the location of the animal within the cylinder had minimal effect on directional cell firing. For each head-direction cell, the preferred direction, peak firing rate, and directional firing range remained stable for days. These results identify a new cell type that signals the animal's head direction in its environment.

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PubMed1990

Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations.

The discharge characteristics of postsubicular head-direction cells in a fixed environment were described in the previous paper (Taube et al., 1990). This paper reports changes in the firing properties of head-direction cells following changes in the animal's environment. Head-direction cells were recorded from rats as they moved freely in a 76-cm-diameter gray cylinder. A white card, occupying 100 degrees of arc, was taped to the inside wall of the cylinder and served as the major orienting spatial cue in the animal's environment. Rotation of the cue card produced near-equal rotation in the preferred firing direction of head-direction cells, with minimal changes in peak firing rate, directional firing range, or asymmetry of the firing-rate/head-direction function. Card removal had no effect on peak firing rate or range of firing, but in 8/13 cells the preferred direction rotated by at least 24 degrees. Similarly, changing the shape of the environment to a rectangular or square enclosure caused the preferred firing direction to rotate by at least 48 degrees for 8/10 cells in the rectangle and 3/8 cells in the square, with minimal changes in the peak firing rate or directional firing range. Hand holding the animals and moving them around the cylinder had no effect on the preferred direction or firing range of the cell, but decreased the maximal firing rate in 7/9 cells. On 2 occasions, 2 head-direction cells were recorded simultaneously. The rotation of the preferred firing direction for one cell was the same as the rotation of the preferred direction for the second cell after each environmental manipulation. These results demonstrate that specific visual cues in the environment can exert control over the preferred firing direction and indicate that head-direction cell firing is not a simple sensory response to visual cues, but rather represents more abstract information concerning the animal's spatial relationship with its environment. The constancy of the angle between the preferred firing directions of pairs of simultaneously recorded head-direction cells suggests that there is a fixed mapping of the population onto direction within the environment. Thus, environmental manipulations appear to cause only a change in the reference direction, but leave all other discharge characteristics of directional cells unchanged. In the discussion, comparisons are drawn between the responses of head-direction cells and hippocampal place cells to similar environmental manipulations (Muller and Kubie, 1987), and ways in which these 2 spatial systems interact in navigation are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)

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PubMed1990

Spatial firing properties of hippocampal theta cells.

Previous studies have shown that complex-spike cells, the most common cell type recorded in the hippocampus of freely moving rats, have the property of spatial firing--that is, a cell will fire rapidly only when the animal is in a particular part of its environment (O'Keefe and Dostrovsky, 1971). In the current study, we analyze the spatial firing of theta cells, the second major class of cells in the hippocampus, which are thought to correspond to nonpyramidal neurons (Fox and Ranck, 1975, 1981). Our purposes were to extend findings from earlier spatial analyses (McNaughton et al., 1983; Christian and Deadwyler, 1986), and to determine whether the spatial firing is cell specific and independent of behavior. Theta cells were recorded from rats in a cylindrical enclosure using techniques previously used for the analysis of spatial firing in complex-spike cells (Muller et al., 1987). The spatial firing patterns of individual neurons appeared as a complex surface with several regions of high and low firing. The ratio of firing from high- to low-rate regions averaged 2.5. These spatial firing patterns were smooth and reproducible, but less so than for complex-spike cells. When a cue card on the wall was moved, theta cell firing patterns remained in register with the cue. Two analyses were performed to determine whether spatial firing patterns were secondary to spatial distributions of behavior. When only locomotor data segments were selected, spatial variations were more clear-cut. In an attempt to test whether theta cells had cell-specific patterns of firing, pairs of theta cells were recorded simultaneously. On all occasions, the firing distribution for each of the cells in a pair was clearly distinctive. These findings support the conclusions that theta cell activity contains a spatial signal that is cell specific and not secondary to other firing correlates.

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PubMed1990

The firing of hippocampal place cells in the dark depends on the rat's recent experience.

Hippocampal "place cells" fire when a freely moving rat is in a given location. The firing of these cells is controlled by visual and nonvisual environmental cues. The effects of darkness on the firing of place cells was studied using the task of Muller et al. (1987), in which rats were trained to chase randomly scattered food pellets in a cylindrical drum with a white cue-card attached to the wall. The position of the rats was tracked via an infrared LED on the headstage with a video system linked to computer. Two experimental protocols were used: in the first, lights were turned off after the rat had already been placed in the chamber; in the second, the rat was placed in the darkened chamber. The dark segments produced by these 2 methods were identical with respect to light and other cues but differed with respect to the rat's experience. The firing patterns of 24 of 28 cells were unaffected by darkness when it was preceded by a light period. In contrast, the firing patterns of 14 of 22 cells changed dramatically when the rats were put into the darkened chamber. Furthermore, the majority of cells that changed their firing pattern in initial darkness maintained that change when the lights were turned on. These results show that place cells can fire differently in identical cue situations and that the best predictor of firing pattern is a combination of current cues and the rat's recent experience. The results are discussed in terms of mnemonic properties of hippocampal cells and "remapping" of place cell representations.

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PubMed1990

Firing properties of hippocampal neurons in a visually symmetrical environment: contributions of multiple sensory cues and mnemonic processes.

The location-specific firing of hippocampal place cells can easily be brought under the control of experimenter-defined cues. Nevertheless, there is evidence that these firing fields are not determined just by immediate sensory input, but also by earlier states of the nervous system (O'Keefe and Speakman, 1987). Here, we report further on the roles of multiple visual cues and mnemonic processes in determining the firing of place cells. Rats were trained to chase food pellets in a cylinder with homogeneous gray walls and 1 white cue card. After a cell's field was recorded in this "standard" condition, probe sessions were conducted in which a second card was placed 180 degrees away from the first. This configuration created a diametrically symmetrical environment in which pairs of locations 180 degrees apart were identical with respect to views of the wall and cards. If place cells are strongly controlled by these immediately available views, firing in the 2-card configuration should be diametrically symmetrical. Alternatively, because the rat moves freely in the cylinder, information is available that pairs of visually identical places are not truly the same. If some mnemonic process stores and updates information about the rat's paths during the session, it is possible that the firing pattern will be different in 2 such places, especially because the original training was conducted in the 1-card, asymmetrical environment. Thirteen of 18 cells had a single, asymmetric firing pattern after the second card was introduced; the field was the same size and shape as in the 1-card configuration and in the same spatial relation to 1 of the 2 cards. The field position during 2-card sessions could be rotated 180 degrees by starting the rat by one card or the other. In further probe sessions in which the cue cards, entry location, and background cues were, in various combinations, rotated in relation to each other, these cells always showed a single field, similar in size and shape to that in the standard, and in the same relationship as in the standard to as many cues as possible. The remaining 5 cells showed complex changes over repeated 2-card sessions, and 3 of these showed paired fields, 180 degrees apart for at least some of the sessions. In one case, the second field disappeared with repeated exposures to 2 cards; in another, the second field persisted when only 1 card was used. We conclude that place cells are influenced both by the immediate sensory configuration and by internal neural states related to earlier experience in the environment.

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PubMed1989

The firing of hippocampal place cells predicts the future position of freely moving rats.

Direct observation and automatic, video-based methods reveal that a large fraction of hippocampal pyramidal neurons recorded from freely moving rats behave as "place cells"; the firing of each place cell occurs almost exclusively when the rat is in a restricted part of its current environment. In earlier work, 2-dimensional firing distributions for place cells over the apparatus area were made under the assumption that the correct location for each spike was the animal's position at the instant that the spike was fired. Spatial firing distributions generated in this way often have a very simple structure, in which the single region of intense activity has a just one maximum, and where the rate decreases monotonically in all directions away from the maximum. We will refer to patterns of this sort as "ideal." We describe how the spatial firing pattern is altered by assigning spikes to positions earlier or later than the instant at which they were fired. Spatial firing distributions were generated for a range of constant displacements of the spike time-series against the position time series. Three quantitative measures were used to estimate the extent to which the spatial firing pattern at different "spike/position shifts" approximated the ideal pattern. The 3 measures are in agreement that spikes must precede the animal's position by about 120 msec for the spatial firing pattern to be closest to the ideal. These results suggest that hippocampal unit activity predicts the animal's future location on a short time scale.

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PubMed1987

Spatial firing patterns of hippocampal complex-spike cells in a fixed environment.

A TV/computer technique was used to simultaneously track a rat's position in a simple apparatus and record the firing of single hippocampal complex-spike neurons. The primary finding is that many of these neurons behave as "place cells," as first described by O'Keefe and Dostrovsky (1971) and O'Keefe (1976). Each place cell fires rapidly only when the rat is in a delimited portion of the apparatus (the cell's "firing field"). In agreement with O'Keefe (1976) and many other authors, we have seen that the firing of place cells is highly correlated with the animal's position and is remarkably independent of other aspects of the animal's behavioral state. Several properties of firing fields were characterized. Firing fields are stable over long time intervals (days) if the environment is constant. They come in several shapes when the animal is in a cylindrical apparatus; moreover, the set of field shapes is different when the animal is in a rectangular apparatus. It also seems that a single cell may have more than one field in a given apparatus. By collecting a sample of 40 place cells in a fixed environment, it has been possible to describe certain features of the place cell population, including the spatial distribution of fields within the apparatus, the average size of fields, and the "intensity" of fields (as measured by maximum firing rate). We also tested the hypothesis that the firing rate of each place cell signals the animal's distance from a point (the field center) so that a weighted average of the firing of the individual cells encodes the animal's position within the apparatus. The animal's position, calculated according to this "distance hypothesis," is systematically different from the animal's true position; this implies that the hypothesis in its simplest form is wrong.

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PubMed1987

The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells.

Using the techniques set out in the preceding paper (Muller et al., 1987), we investigated the response of place cells to changes in the animal's environment. The standard apparatus used was a cylinder, 76 cm in diameter, with walls 51 cm high. The interior was uniformly gray except for a white cue card that ran the full height of the wall and occupied 100 degrees of arc. The floor of the apparatus presented no obstacles to the animal's motions. Each of these major features of the apparatus was varied while the others were held constant. One set of manipulations involved the cue card. Rotating the cue card produced equal rotations of the firing fields of single cells. Changing the width of the card did not affect the size, shape, or radial position of firing fields, although sometimes the field rotated to a modest extent. Removing the cue card altogether also left the size, shape, and radial positions of firing fields unchanged, but caused fields to rotate to unpredictable angular positions. The second set of manipulations dealt with the size and shape of the apparatus wall. When the standard (small) cylinder was scaled up in diameter and height by a factor of 2, the firing fields of 36% of the cells observed in both cylinders also scaled, in the sense that the field stayed at the same angular position and at the same relative radial position. Of the cells recorded in both cylinders, 52% showed very different firing patterns in one cylinder than in the other. The remaining 12% of the cells were virtually silent in both cylinders. Similar results were obtained when individual cells were recorded in both a small and a large rectangular enclosure. By contrast, when the apparatus floor plan was changed from circular to rectangular, the firing pattern of a cell in an apparatus of one shape could not be predicted from a knowledge of the firing pattern in the other shape. The final manipulations involved placing vertical barriers into the otherwise unobstructed floor of the small cylinder. When an opaque barrier was set up to bisect a previously recorded firing field, in almost all cases the firing field was nearly abolished. This was true even though the barrier occupied only a small fraction of the firing field area. A transparent barrier was effective as the opaque barrier in attenuating firing fields. The lead base used to anchor the vertical barriers did not affect place cell firing.(ABSTRACT TRUNCATED AT 400 WORDS)

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