Place cells and place navigation

The assumption that hippocampal place cells (PCs) form the neural substrate of cognitive maps can be experimentally tested by comparing the effect of experimental interventions on PC activity and place navigation. Conditions that interfere with place navigation (darkness, cholinergic blockade) but leave PC activity unaffected obviously disrupt spatial memory at a post-PC level. Situations creating a conflict between egocentric and allocentric orientation (place navigation in the Morris water maze filled with slowly rotating water) slow down spatial learning. PC recording in rats searching food pellets in a rotating arena makes it possible to determine which firing fields are stable relative to the room (allocentrically dependent on sighted extramaze landmarks), to the surface of the arena (dependent on egocentric path integration mechanisms and intra-arena cues), or disappear during rotation. Such comparison is made possible by the computerized tracking system simultaneously displaying a rat's locomotion and the respective firing rate maps both in the room reference and arena reference frames. More severe conflict between allocentric and egocentric inputs is produced in the field clamp situation when the rat searching food in a ring-shaped arena is always returned by rotation of the arena to the same allocentric position. Ten-minute exposure to this condition caused subsequent disintegration or remapping of 70% PCs (n = 100). Simultaneous examination of PC activity and navigation is possible in the place avoidance task. A rat searching food in a stationary or rotating arena learns to avoid an allocentrically or egocentrically defined location where it receives mild electric footshock. In the place preference task the rat releases pellet delivery by entering an unmarked goal area and staying in it for a criterion time. Both tasks allow direct comparison of the spatial reference frames used by the PCs and by the behaving animal.     

Comparisons of head direction cell activity in the postsubiculum and anterior thalamus of freely moving rats

Single cells in the rat anterior thalamic nucleus (ATN) and postsubiculum (PoS) discharge as a function of the rat's directional heading in the horizontal plane, independent of its location. A previous study that compared cell firing during clockwise and counterclockwise head turns concluded that ATN 'head direction' (HD) cell discharge anticipates the rat's future directional heading, while PoS HD cell discharge is in register with the rat's current directional heading (Blair and Sharp [1995] J Neurosci 15:6260-6270). In the current study we extend these findings by using a different method of analysis. HD cells in the ATN and PoS were first characterized by three different measures: peak firing rate, range width, and information content. We then examined how these measures varied when cell firing was aligned with past (negative time shift) or future (positive time shift) head direction of the rat. We report that all three measures were optimized when ATN cell firing was aligned with the animal's future directional heading by about +23 msec. In contrast, PoS HD cell firing was optimized when cell firing was aligned with the rat's past head direction by about -7 msec. When the optimal value was plotted as a function of the amount of time spikes were shifted relative to head orientation, the mean ATN function was shifted to the right of the PoS function only at negative time shifts; at positive time shifts the two functions overlapped. Analysis of two recording sessions from the same cell indicated that each cell in a particular brain area is 'tuned' to a specific time shift so that all cells within a brain area are not uniformly tuned to the same time shift. Other analyses showed that the clockwise and counterclockwise tuning functions were not skewed in the direction of the head turn as postulated by Redish et al. ([1996] Network: Computation in Neural Systems 7:671-685) and Blair et al. ([1997] J Neurophysiol 17:145-159). Additional analysis on episodes when the rat happened to continually point its head in the preferred direction indicated that HD cell firing undergoes little adaptation. In the Discussion, we argue that these results are best accounted for by a motor efference copy signal operating on both types of HD cells such that the copy associated with the PoS HD cells is delayed in time by about 30 msec relative to the copy associated with ATN HD cells.     

Place cells recorded in the parasubiculum of freely moving rats

Previous studies have identified neurons in the hippocampus, subiculum, and entorhinal cortex which discharge as a function of the animal's location in the environment. In contrast, neurons in the postsubiculum and anterior thalamic nucleus discharge as a function of the animal's head direction in the horizontal plane, independent of its behavior and location in the environment. Because the parasubiculum (PaS) has extensive connections, either directly or indirectly, with these structures, it is centrally located to influence the neuronal activity in these areas. This study was therefore designed to determine the types of behavioral and spatial correlates in neurons from the PaS. Single unit recordings were conducted in the PaS of freely moving rats trained to retrieve food pellets thrown randomly into a cylindrical apparatus. A total of 10.3% of the cells were classified as place cells because they discharged in relation to the animal's location in the cylinder. A large percentage of cells (41.4%) were classified as theta cells. The remaining cells had nondiscernable behavioral correlates. Quantitative analysis of the firing rate maps for the place cells showed they had higher levels of background activity and contained larger firing fields than values reported previously for hippocampal place cells. Directional analysis showed that only three out of 16 cells contained a secondary directional correlate; the firing rate for the remaining cells was not affected by the animal's directional heading within the firing field. A time shift analysis, which shifted the spike time series relative to the animal location series, was conducted to determine whether the quality of the location-specific firing could be improved. The time shifts for three different spatial parameters were optimal when cell discharge led the animal's position. Furthermore, the optimal time shifts for two of these parameters (firing area and information content) were less than the optimal shift reported for hippocampal place cells and suggested that PaS cell discharge lagged behind hippocampal place cell activity. Rotation of the cue card with the animal out of view led to near equal rotation of the firing field when the animal was returned to the apparatus. These results indicate that a small population of cells in the PaS encode the animal's location in its environment, although the representation of space encoded by these cells is different from the type of representation encoded by hippocampal place cells.     

Place cell discharge is extremely variable during individual passes of the rat through the firing field

The idea that the rat hippocampus stores a map of space is based on the existence of "place cells" that show "location-specific" firing. The discharge of place cells is confined with remarkable precision to a cell-specific part of the environment called the cell's "firing field." We demonstrate here that firing is not nearly as reliable in the time domain as in the positional domain. Discharge during passes through the firing field was compared with a model with Poisson variance of the location-specific firing determined by the time-averaged positional firing rate distribution. Place cells characteristically fire too little or too much compared with expectations from the random model. This fundamental property of place cells is referred to as "excess firing variance" and has three main implications: (i) Place cell discharge is not only driven by the summation of many small, asynchronous excitatory synaptic inputs. (ii) Place cell discharge may encode a signal in addition to the current head location. (iii) The excess firing variance helps explain why the errors in computing the rat's position from the simultaneous activity of many place cells are large.     

Correlation between head direction cell activity and spatial behavior on a radial arm maze.

This study assessed the activity of head direction (HD) cells during performance of a spatial reference memory task on a radial arm maze. Rats were trained to select a maze arm located in a constant position in relation to a salient extramaze visual landmark. HD cell discharge properties remained relatively stable across task acquisition in most rats. Following acquisition, rotation of the landmark by 90° or 180° usually led to a corresponding shift in the maze arm selected and the HD cell's preferred firing direction. When the cell's preferred direction did not shift, rats usually selected the wrong arm. HD cell activity was not influenced by the rat's approach to the goal, reward consumption, or exit from the reward area. This demonstration of landmark control over behavior and the cell's preferred direction supports the hypothesis that HD cells contribute to an absolute representation of the environment that can be used to guide spatial behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Firing properties of rat lateral mammillary single units: head direction, head pitch, and angular head velocity

Many neurons in the rat anterodorsal thalamus (ADN) and postsubiculum (PoS) fire selectively when the rat points its head in a specific direction in the horizontal plane, independent of the animal's location and ongoing behavior. The lateral mammillary nuclei (LMN) are interconnected with both the ADN and PoS and, therefore, are in a pivotal position to influence ADN/PoS neurophysiology. To further understand how the head direction (HD) cell signal is generated, we recorded single neurons from the LMN of freely moving rats. The majority of cells discharged as a function of one of three types of spatial correlates: (1) directional heading, (2) head pitch, or (3) angular head velocity (AHV). LMN HD cells exhibited higher peak firing rates and greater range of directional firing than that of ADN and PoS HD cells. LMN HD cells were modulated by angular head velocity, turning direction, and anticipated the rat's future HD by a greater amount of time (approximately 95 msec) than that previously reported for ADN HD cells (approximately 25 msec). Most head pitch cells discharged when the rostrocaudal axis of the rat's head was orthogonal to the horizontal plane. Head pitch cell firing was independent of the rat's location, directional heading, and its body orientation (i.e., the cell discharged whenever the rat pointed its head up, whether standing on all four limbs or rearing). AHV cells were categorized as fast or slow AHV cells depending on whether their firing rate increased or decreased in proportion to angular head velocity. These data demonstrate that LMN neurons code direction and angular motion of the head in both horizontal and vertical planes and support the hypothesis that the LMN play an important role in processing both egocentric and allocentric spatial information.     

The dynamic nature of spatial encoding in the hippocampus.

Many hippocampal neurons (place cells) appear to represent a particular location within an environment (their place field). This property would appear to be central to hippocampal involvement in navigation based on spatial memory. Although a navigationally useful representation might also include information about distal goals, having a place field and being able to represent a distal goal would appear to be mutually exclusive place cell properties. Our simulations demonstrate, however, that information about goal direction can be simply derived from the changes in place field density that occur when place fields shift location in a goal-directed manner. Previous reports that place fields respond dynamically to shifts in goal location may, therefore, represent the operation of such a system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactions between idiothetic cues and external landmarks in the control of place cells and head direction cells

Two types of neurons in the rat brain have been proposed to participate in spatial learning and navigation: place cells, which fire selectively in specific locations of an environment and which may constitute key elements of cognitive maps, and head direction cells, which fire selectively when the rat's head is pointed in a specific direction and which may serve as an internal compass to orient the cognitive map. The spatially and directionally selective properties of these cells arise from a complex interaction between input from external landmarks and from idiothetic cues; however, the exact nature of this interaction is poorly understood. To address this issue, directional information from visual landmarks was placed in direct conflict with directional information from idiothetic cues. When the mismatch between the two sources of information was small (45 degrees), the visual landmarks had robust control over the firing properties of place cells; when the mismatch was larger, however, the firing fields of the place cells were altered radically, and the hippocampus formed a new representation of the environment. Similarly, the visual cues had control over the firing properties of head direction cells when the mismatch was small (45 degrees), but the idiothetic input usually predominated over the visual landmarks when the mismatch was larger. Under some conditions, when the visual landmarks predominated after a large mismatch, there was always a delay before the visual cues exerted their control over head direction cells. These results support recent models proposing that prewired intrinsic connections enable idiothetic cues to serve as the primary drive on place cells and head direction cells, whereas modifiable extrinsic connections mediate a learned, secondary influence of visual landmarks.     

Place navigation by rats in a swimming pool.

Describes characteristics of place navigation by rats in the Morris water task. Ss learned to find a small invisible platform in a large, circular swimming pool to escape from cool milk. A variety of spatial localization strategies, including spatial mapping, response sequencing, and distal cue navigational strategies, were demonstrated. Using variants of this task, the following was demonstrated: (a) Rats very readily learned true mapping strategies, being able to swim directly to the invisible platform from anywhere in the pool after only a few trials; this ability was not dependent on navigating by specific distal cues nor on starting from a familiar place. (b) Ss acquired information that facilitated subsequent place navigation merely by viewing the room from the location of the invisible goal. (c) The location of the invisible platform was remembered extremely well for several weeks. (d) The availability of only distal auditory beacons permitted acquisition of an accurate spatial mapping strategy. (e) A single S could acquire both mapping and nonmapping strategies in the swimming pool and apply them when required by the situation. Results emphasize the utility of the Morris water task and demonstrate some of the basic features of mapping and nonmapping strategies in solving a variety of spatial problems. (French abstract) (18 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanisms of reorientation and object localization by children: A comparison with rats.

Neurophysiological studies show that the firing of place and head-direction (HD) cells in rats can become anchored to features of the perceptible environment, suggesting that those features partially specify the rat's position and heading. In contrast, behavioral studies suggest that disoriented rats and human children rely exclusively on the shape of their surroundings, ignoring much of the information to which place and HD cells respond. This difference is explored in the current study by investigating young children's ability to locate objects in a square chamber after disorientation. Children 18–24 months old used a distinctive geometric cue but not a distinctively colored wall to locate the object, even after they were familiarized with the colored wall. Results suggest that the spatial representations underlying reorientation and object localization are common to humans and other mammals. Together with the neurophysiological findings, these experiments raise questions for the hypothesis that hippocampal place and HD cells serve as a general orientation device for target localization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Abnormal hippocampal spatial representations in alphaCaMKIIT286A and CREBalphaDelta- mice

Hippocampal "place cells" fire selectively when an animal is in a specific location. The fine-tuning and stability of place cell firing was compared in two types of mutant mice with different long-term potentiation (LTP) and place learning impairments. Place cells from both mutants showed decreased spatial selectivity. Place cell stability was also deficient in both mutants and, consistent with the severities in their LTP and spatial learning deficits, was more affected in mice with a point mutation [threonine (T) at position 286 mutated to alanine (A)] in the alpha calmodulin kinase II (alphaCaMKIIT286A) than in mice deficient for the alpha and Delta isoforms of adenosine 3'5'-monophosphate-responsive element binding proteins (CREBalphaDelta-). Thus, LTP appears to be important for the fine tuning and stabilization of place cells, and these place cell properties may be necessary for spatial learning.     

Hippocampal cell firing correlates of delayed-match-to-sample performance in the rat

Hippocampal CA1 and CA3 neurons were recorded in rats performing a delayed-match-to-sample (DMTS) task. Complex spike cells showed significant firing peaks following sample and match responses and during delivery of water reward. Individual cells were classified into 4 subtypes according to the presence or absence of firing in each of these 3 phases. There were significant differences in delay interval firing among the 4 subtypes, but firing during the delay did not predict the correct response: 34% of the cells showed a linear change in firing during the delay. Further analyses revealed significant lever position firing biases in approximately 70% of the cells tested irrespective of subtype. The complexity of firing correlates of the neurons recorded in this DMTS task suggests that the hippocampus divides specific aspects of the performance demands of the task across different cell subtypes, which together provide sufficient information to resolve the matching-to-sample problem on any given trial.     

Learning about environmental geometry: An associative model.

K. Cheng (1986) suggested that learning the geometry of enclosing surfaces takes place in a geometric module blind to other spatial information. Failures to find blocking or overshadowing of geometry learning by features near a goal seem consistent with this view. The authors present an operant model in which learning spatial features competes with geometry learning, as in the Rescorla-Wagner model. Relative total associative strength of cues at a location determines choice of that location and thus the frequencies of reward paired with each cue. The model shows how competitive learning of local features and geometry can appear to result in potentiation, blocking, or independence, depending on enclosure shape and kind of features. The model reproduces numerous findings from dry arenas and water mazes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Blocking and overshadowing in human geometry learning.

In a two-dimensional computer-based search task, human participants were required to learn the location of a goal by using the geometric information available on the screen. When the goal location was defined by two shapes that differed in salience, the more salient shape overshadowed learning based on the less salient shape but not the other way round. Furthermore, when one shape was pretrained as a signal for the location of the goal, learning about the geometric cues of the other shape was blocked. These results suggest that spatial learning based on geometry is ruled by associative principles and support learning models that do not invoke a special status for geometric cues (e.g., Miller & Shettleworth, 2007). (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Brain aging: impaired coding of novel environmental cues

Studies of the spatial memory capacities of aged animals usually focus on performance during the learning of new environments. By contrast, efforts to characterize age-related alterations in spatial firing information processing by hippocampal neurons typically use an environment that is highly familiar to the animals. In the present study we compared the firing properties of hippocampal neurons in young adult and aged rats as they acquired spatial information about new environmental cues. Hippocampal complex spike cells were recorded while rats performed a radial arm maze task in a familiar environment and then recorded again after many of the spatial cues were changed. After the change in the environment, in aged rats 35-42% of place fields retained their original shape and location with respect to the maze center, although they usually rotated to another arm. By contrast, all place fields in young animals either disappeared or appeared in a new location. Some of the new place fields appeared in the new environment during the first 5 min of exploration, whereas others needed more than 30 min to develop fully. In the familiar environment spatial selectivity of place cells was similar in young and aged rats. By contrast, when rats were placed into a new environment, spatial selectivity decreased considerably in aged memory-impaired rats compared with that of young rats and aged rats with intact memory performance.     

Landmark control and updating of self-movement cues are largely maintained in head direction cells after lesions of the posterior parietal cortex.

Head direction (HD) cells discharge as a function of the rat's directional orientation with respect to its environment. Because animals with posterior parietal cortex (PPC) lesions exhibit spatial and navigational deficits, and the PPC is indirectly connected to areas containing HD cells, we determined the effects of bilateral PPC lesions on HD cells recorded in the anterodorsal thalamus. HD cells from lesioned animals had similar firing properties compared to controls and their preferred firing directions shifted a corresponding amount following rotation of the major visual landmark. Because animals were not exposed to the visual landmark until after surgical recovery, these results provide evidence that the PPC is not necessary for visual landmark control or the establishment of landmark stability. Further, cells from lesioned animals maintained a stable preferred firing direction when they foraged in the dark and were only slightly less stable than controls when they self-locomoted into a novel enclosure. These findings suggest that PPC does not play a major role in the use of landmark and self-movement cues in updating the HD cell signal, or in its generation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A simple network model simulates hippocampal place fields: Parametric analyses and physiological predictions.

Hippocampal place cells may be the computational units of a neuronal cognitive mapping system. A network model trained to compute locations from distal cues simulated the defining properties of hippocampal place cells (i.e., place-specific activation). The model produced units with detailed properties of place cells, including multiple subfields, "silent" and "noisy" cells, fields that persisted after cue removal, and groups of simulated field that overlapped in multiple clusters. Quantitative variants of the model showed that different properties of the fields were influenced by the complexity of the visual input (the number of spatial cues), the available computational resources (the number of hidden units), and the output encoding used to represent location. The simulations provide a framework for testing relationships between place field properties, variations in spatial environments, and the integrity of the hippocampal system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Angular velocity and head direction signals recorded from the dorsal tegmental nucleus of gudden in the rat: Implications for path integration in the head direction cell circuit.

When a rat navigates through space, head direction (HD) cells provide an ongoing signal of the rat's directional heading. It is thought that these cells rely, in part, on angular path integration of the rat's head movements. This integration requires that the HD cell system receive information about angular head movements and that this information be combined with the current directional signal, to generate the next "predicted" direction. Recent data suggest that the dorsal tegmental nucleus (DTN) may play a critical role in helping to generate the HD cell signal. To test this, recordings were made from cells in the DTN in freely moving rats. The following cell types were found: (a) "classic" HD cells, (b) angular velocity cells, and (c) cells that fired as a function of both head direction and angular velocity. Thus, DTN cells exhibit firing characteristics that are critical to the neural circuit hypothesized for generation of the HD cell signal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal place fields are altered by the removal of single visual cues in a distance-dependent manner.

Hippocampal CA3 cells were recorded in male Long-Evans rats that explored a square recording chamber. Three of the 4 chamber walls held a rectangular cue card, each of different size. Rotating the set of cue cards rotated the location of the place fields. Place fields were common close to the walls of the recording chamber, particularly the walls with cues. When single cues were removed, the spatial information content decreased but returned to baseline levels when the cue was replaced. When a cue near a place field was removed, the place field firing rate and area decreased; when a distant cue was removed, firing rate and area increased. Thus, removing single visual cues predictably and reversibly altered hippocampal place fields. Together, the results suggest that hippocampal neurons may optimize the encoding of visual information and are consistent with a distance-encoding hypothesis of CA3 network function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)