Patricia E. Sharp

Role of the Lateral Mammillary Nucleus in the Rat Head Direction Circuit: A Combined Single Unit Recording and Lesion Study

We recorded head direction (HD) cells from the lateral mammillary nucleus (LMN) and anterior thalamus (ATN) of freely behaving rats and also made bilateral lesions of LMN while recording HD cells from ATN. We discovered that the tuning functions of LMN HD cells become narrower during contraversive head turns, but not ipsiversive head turns, compared to when the head is not turning. This narrowing effect does not occur for ATN HD cells. We also found that the HD signal in LMN leads that in ATN by about 15-20 ms. When LMN was lesioned bilaterally, HD cells in ATN immediately lost their directional firing properties and never recovered them. Based on these findings, we argue that LMN may be an essential component of an attractor-integrator network that participates in generating the HD signal.

Visual and vestibular influences on head-direction cells in the anterior thalamus of the rat.

As a rat navigates through space, head-direction cells provide an ongoing signal of its momentary directional heading. This directional signal is thought to be generated, in part, by a dead-reckoning mechanism that uses angular motion information to constantly update the directional representation. This study investigated what kinds of angular motion information might be used for dead reckoning. Anterior thalamic head-direction cells were recorded from rats in a rotatable, cylindrical chamber, which could independently deliver visual motion cues and vestibular cues. Results suggest that both of these angular motion cues have an influence on head-direction cells and may thus be used for dead reckoning. The authors conclude that vestibular and visual movement cues work interactively, along with visual landmarks and motor signals, to determine the directional frame of reference.

Complimentary roles for hippocampal versus subicular/entorhinal place cells in coding place, context, and events

At least two important questions are posed by the existence of hippocampal place cells. The first of these has to do with how the complex, abstract properties exhibited by these cells can be explained mechanistically. The second has to do with the implications of place cells for our conception of the broader role of the hippocampus in spatial and other behaviors.

Subicular cells generate similar spatial firing patterns in two geometrically and visually distinctive environments: Comparison with hippocampal place cells

Cells in both the hippocampus and the subiculum show location related firing patterns, so that the momentary firing rate of a cell is related to the spatial location of a freely moving rat as it navigates in an environment. Since the subiculum receives a strong anatomical projection from the hippocampus, it seems possible that the subicular cell spatial patterns are simply driven by the spatial signals from hippocampal place cells. Data presented here, however, suggest that the two areas code space in fundamentally different ways. Here, spatial firing patterns of individual hippocampal and subicular cells were studied as rats navigated in two different environments. The two chambers were a cylinder and a square, of equal area. For some rats the two chambers were painted to have similar visual stimulus characteristics, while for others, the two were very different. The subicular cells showed very similar firing patterns in the two chambers, regardless of whether they were visually similar or different. In contrast, as predicted based on the findings of earlier studies, hippocampal place cells showed different patterns in the two (again, regardless of their visual similarity). These results suggest that the subicular cells have the ability to transfer a single, abstract spatial representation from one environment to another. This pattern is stretched to fit within the boundaries of the current environment. Thus, the subicular cells seem to provide a generic representation of the geometric relationships between different locations in an environment. It seems possible that this representation may contribute to some navigational abilities exhibited by animals, such as dead reckoning, and novel route generation in unfamiliar environments. In contrast, it appears that hippocampal place cells provide a spatial representation-which is unique for each environment and which is strongly influenced by the exact details and overall context of the situation.

Computer simulation of hippocampal place cells

Hippocampal pyramidal cells show location-specific firing as animais navigate through an environment. It has been suggested that this firing could resuit from the “local view” available in a cell’s field. Hippocampal damage results in learning deficits on a wide variety of tasks. This, along with the fact that an associative form of plasticity has been discovered in the hippocampus has led to the idea that this structure might serve as a distributed, associative-matrix memory device. Here, these ideas are combined in a model in which pyramidal cells are the output layer of a competitive-learning, pattern-classification device. The inputs are patterns of environmental stimuli as viewed by a computerized “rat” from various locations within a simulated environment. These patterns are “classified” on the basis of their similarity. Since views available from contiguous regions of space are similar, single cells come to fire in a circumscribed region (place field). Firing-rate maps for these theoretical units show place fields remarkably similar to those of actual place cells. Also, they show remarkably similar behavior to that of real cells when tested under some of the probe conditions similar to those which have been used for actual cells.

Stress-Induced Alterations in Hippocampal Plasticity, Place Cells, and Spatial Memory

Acute, inescapable, and unpredictable stress can profoundly modify brain and cognition in humans and animals. The present study investigated the ensuing effects of 2-h variable “audiogenic” stress on three related levels of hippocampal functions in rats: long-term potentiation, place cell activity, and spatial memory. In agreement with prior findings, we observed that stress reduced the magnitude of Schaffer collateral/commissural–Cornu Ammonis field 1 long-term potentiation in vitro, and selectively impaired spatial memory on a hidden platform version of the Morris water maze task. We also observed that stress impaired the stability of firing rates (but not firing locations) of place cells recorded from dorsal Cornu Ammonis field 1 in rats foraging freely on a novel open-field platform located in a familiar surrounding room. These findings suggest that stress-induced modifications in synaptic plasticity may prevent the storage of stable “rate maps” by hippocampal place cells, which in turn may contribute to spatial memory impairments associated with stress.

Movement-related correlates of single cell activity in the interpeduncular nucleus and habenula of the rat during a pellet-chasing task.

The habenula and interpeduncular nucleus (IPN) are part of a dorsal diencephalic conduction system which receives input from cholinergic, striatal, and hypothalamic areas, and sends output to several, disparate midbrain regions. These output regions include the dorsal tegmental nucleus, which is part of a navigation-related system that provides a signal for directional heading. The habenula and IPN also project to the dorsal and medial Raphe nuclei, thought to be involved in mood and behavioral state regulation. Here, cells in both the habenula and IPN were recorded in freely moving rats while they foraged for food pellets. There were four major findings. First, many of the cells tended to fire in sporadic bouts of relatively high versus low rates, and this may be related to intrinsic cell properties discovered during in vitro studies. Second, although these regions are connected to the direction signaling circuit, they do not, themselves demonstrate a directional signal. Third, about 10% of the cells in the lateral habenula showed a strong correlation between rate and angular head motion. This may constitute an important, requisite input to the above-mentioned head direction circuit. Finally, many of the cells in each region showed a temporally coarse correlation with running speed, so that bouts of high frequency firing coincided with episodes of higher behavioral activation. This last finding may be related to work which shows an influence of the habenula on locomotor activity, and in relation to the protective effects of exercise in relation to stress, as mediated by the Raphe nuclei.

Neural network modeling of the hippocampal formation spatial signals and their possible role in navigation: A modular approach.

Cells throughout the hippocampal formation show striking spatial firing correlates as a rat navigates through space. These cells are thought to play a critical role in orchestrating the navigational abilities of the animals, since damage to the hippocampal formation causes spatial learning deficits. Here, we present a theoretical framework aimed at explaining how the different spatial signals are generated, as well as how they may help guide navigational behavior.

Effects of aging on environmental modulation of hippocampal evoked responses.

Evoked responses in the dentate gyrus of the hippocampal formation undergo a long-term enhancement following high-frequency stimulation of the perforant pathway. A similar change results from exposure of animals to a complex spatial environment. The effect of aging on the development and decay of this environmentally induced response enhancement was examined in the present study. Previously it was shown that electrically induced enhancement reaches the same asymptotic level in young and old animals but decays more quickly in old animals. It has been suggested that this faster decay may underlie the faster forgetting of spatial information observed in old animals. Chronic recordings were made from young (14 month) and old (32 month) rats. After exposure to an enriched environment for 11 days, the population spike component of the response increased about 125% over baseline in both groups. No changes were seen in either group in the synaptic component. Following the enrichment treatment, animals were returned to their home cages. The decay of the enhanced population spike during this period differed markedly between age-groups (time constants of 30 and 11 days for the young and old groups, respectively). These results suggest that the factors governing the decay of electrically and environmentally induced response enhancement are similarly affected by the aging process and may share a common mechanism.

Lesions of the mammillary body region severely disrupt the cortical head direction, but not place cell signal

The rat limbic system contains a variety of location (place and grid) cells and directional (head direction; HD) cells, thought to be critical for navigation. The HD cells can be found throughout many portions of the hippocampal formation, as well as additional limbic cortical and subcortical regions. These HD‐containing regions are generally strongly interconnected anatomically. Earlier work, along with theoretical considerations, suggest that despite the ubiquitous presence of HD cells, there may be a single region which is critical for the initial formation of this HD signal. Specifically, it has been suggested that the critical HD cell network resides in a reciprocal loop formed by the interconnected lateral mammillary nucleus and dorsal tegmental nucleus of Gudden. Unlike the HD cells, place cells have not been observed in subcortical structures. They are, however, found in various forms throughout much of the hippocampal formation. Theoretical accounts of the place cells suggest that they are partly dependent on a path integration process which is, in turn, dependent on the HD cells. According to the above reasoning, lesions of the mammillary bodies should completely eliminate both HD and place/grid cells in the hippocampal formation. Here, we tested for both HD and place cell activity in various hippocampal formation sub regions following lesions of the mammillary bodies. We found that these lesions caused nearly complete elimination of the HD cell signal, but left the place cell signal largely intact. Our interpretation of these findings is somewhat limited by the fact that we did not provide a thorough test of the path integration abilities of the post lesion place cells. These findings pose a challenge for current theoretical accounts of place and grid cells. They also help to explain the role played by the mammillary bodies in spatial learning and memory.