Sheri J. Y. Mizumori

Directionally selective mnemonic properties of neurons in the lateral dorsal nucleus of the thalamus of rats

The hippocampal formation has been extensively studied for its special role in visual spatial learning and navigation. To ascertain the nature of the associations made, or computations performed, by hippocampus, it is important to delineate the functional contributions of its afferents. Therefore, single units were recorded in the lateral dorsal nucleus of the thalamus (LDN) as rats performed multiple trials on a radial maze. Many LDN neurons selectively discharged when an animals head was aligned along particular directions in space, irrespective of its location in the test room. These direction-sensitive cells were localized to the dorsal aspect of the caudal two-thirds of the LDN, the site of innervation by retinal recipient pretectal and intermediate/deep-layer superior colliculus cells (Thompson and Robertson, 1987b). The directional specificity and preference of LDN cells were disrupted if rats were placed on the maze in darkness. If the room light was then turned on, the original preference was restored. If the light was again turned off, directional firing was maintained briefly. Normal directional firing lasted about 2–3 min. After this time, the directional preference (but not specificity) appeared to “rotate” systematically in either the clockwise or counterclockwise direction. The duration of normal directional discharge patterns in darkness could be extended to 30 min by varying the behavior of the animal. LDN cells required visual input to initialize reliable directional firing. After the rat viewed the environment, directional specificity was maintained in the absence of visual cues. Maximal directional firing was achieved only when the rat viewed the entire test room, and not just the scene associated with the directional preference of the cell. Thus, contextual information seems important. Also, a significant correlation was found between directional specificity and errors made on the maze during acquisition of the task. It was concluded that the LDN may pass on to the hippocampal formation directional information that is not merely a reflection of current sensory input. As such, the LDN may serve an important integrative function for limbic spatial learning systems.

Neurons in rat medial prefrontal cortex show anticipatory rate changes to predictable differential rewards in a spatial memory task

The present study electrophysiologically examined the contribution of prelimbic and infralimbic neurons in the medial prefrontal cortex (mPFC) to integration of reward and spatial information while rats performed multiple memory trials on a differentially rewarded eight arm radial maze. Alternate arms consistently held one of two different reward amounts. Similar to previous examinations of the rat mPFC, few cells showed discrete place fields or altered firing during a delay period. The most common behavioral correlate was a change in neuronal firing rate prior to reward acquisition at arm ends. A small number of reward-related cells differentiated between high and low reward arms. The presence of neurons that anticipate expected reward consequences based on information about the spatial environment is consistent with the hypothesis that the mPFC is part of a neural system which merges spatial information with its motivational significance.

Hippocampal Representational Organization and Spatial Context

The hippocampus appears to undergo continual representational reorganization as animals navigate their environments. This reorganization is postulated to be reflected spatially in terms of changes in the ensemble of place cells activated, as well as changes in place field specificity and reliability for cells recorded in both hilar/CA3 and CA1 regions. The specific contribution of the hilar/CA3 region is suggested to be to compare the expected spatial context with that currently being experienced, then relay discrepancies to CA1. The properties of CA1 place fields in part reflect the spatial comparisons made in the hilar/CA3 area. In addition, CA1 organizes the input received from the hilar/CA3 place cells according to different temporal algorithms that are unique to different tasks. In this way, hippocampus helps to distinguish temporally one spatial context from another, thereby contributing to episodic memories. Hippocampus 1999;9:444–451.

Finding your way in the dark: the retrosplenial cortex contributes to spatial memory and navigation without visual cues.

Path integration is presumed to rely on self-motion cues to identify locations in space and is subject to cumulative error. The authors tested the hypothesis that rats use memory to reduce such errors and that the retrosplenial cortex contributes to this process. Rats were trained for 1 week to hoard food in an arena after beginning a trial from a fixed starting location; probe trials were then conducted in which they began a trial from a novel place in light or darkness. After control injections, rats searched around the training location, showing normal spatial memory. Inactivation of the retrosplenial cortex disrupted this search preference. To assess accuracy during navigation, rats were then trained to perform multiple trials daily, with a fixed or a different starting location in light or darkness. Retrosplenial cortex inactivation impaired accuracy in darkness. The retrosplenial cortex may provide mnemonic information, which decreases errors when navigating in the dark.

Characteristics of basolateral amygdala neuronal firing on a spatial memory task involving differential reward

Previous research has shown that spatial, movement, and reward information is integrated within the ventral striatum (VS). The present study examined the possible contribution of the basolateral nuclei of the amygdala (BLA) to this interaction by examining behavioral correlates of BLA neurons while rats performed multiple memory trials on an 8-arm radial maze. Alternate arms consistently held 1 of 2 different amounts of reward. Recorded cells were correlated with motion, auditory input, space, and reward acquisition. Reward-related units were found that anticipated reward encounter, that responded during reward consumption, and that differentiated between high and low reward magnitude. This is consistent with the hypothesis that BLA neurons may provide the VS with reward-related information that could then be integrated with spatial information to ultimately affect goal-directed behavior.

Redistribution of Spatial Representation in the Hippocampus of Aged Rats Performing a Spatial Memory Task

Young and old rats performed on a maze according to a forced-choice and then a spatial memory procedure either in the same or a different environment. Aged rats were slower to learn the spatial memory task when tested in the same, but not in a different, room. One interpretation of this pattern of results is that although old rats learn new rules as quickly as young rats, they show less flexibility with old rules and familiar spatial information. Impaired choice accuracy during asymptote performance suggests poor processing of trial-unique information by old rats. Spatial correlates of hippocampal CA1 and hilar cells varied with task demand: CA1 cells of aged rats showed more spatially selective place fields, whereas hilar cells showed more diffuse location coding during spatial memory, and not forced-choice, tests. Such representational reorganization may reflect a compensatory response to age-related neurobiological changes in hippocampus.

A neural systems analysis of adaptive navigation.

In the field of the neurobiology of learning, significant emphasis has been placed on understanding neural plasticity within a single structure (or synapse type) as it relates to a particular type of learning mediated by a particular brain area. To appreciate fully the breadth of the plasticity responsible for complex learning phenomena, it is imperative that we also examine the neural mechanisms of the behavioral instantiation of learned information, how motivational systems interact, and how past memories affect the learning process. To address this issue, we describe a model of complex learning (rodent adaptive navigation) that could be used to study dynamically interactive neural systems. Adaptive navigation depends on the efficient integration of external and internal sensory information with motivational systems to arrive at the most effective cognitive and/or behavioral strategies. We present evidence consistent with the view that during navigation: 1) the limbic thalamus and limbic cortex is primarily responsible for the integration of current and expected sensory information, 2) the hippocampal-septal-hypothalamic system provides a mechanism whereby motivational perspectives bias sensory processing, and 3) the amygdala-prefrontal-striatal circuit allows animals to evaluate the expected reinforcement consequences of context-dependent behavioral responses. Although much remains to be determined regarding the nature of the interactions among neural systems, new insights have emerged regarding the mechanisms that underlie flexible and adaptive behavioral responses.

Convergence of head direction and place information in the CA1 region of hippocampus.

The hippocampus has long been considered critical for spatial learning and navigation. Recent theoretical models of the rodent and primate hippocampus consider spatial processing a special case of a more general memory function. These non-spatial theories of hippocampus differ from navigational theories with respect to the role of self-motion representations. The present study presents evidence for a new cell type in the CA1 area of the rat hippocampus that codes for directional heading independent of location information (i.e. the angular component of self-motion). These hippocampal head direction cells are controlled by external and idiothetic cues in a similar way as head direction cells in other brain areas and hippocampal place cells. Convergent head direction information and location information may be an essential component of a neural system that monitors behavioral sequences during navigation. Conflicts between internally generated and external cues have previously been shown to result in new hippocampal place representations, suggesting that head direction information may participate in synaptic interactions when new location codes are formed. Combined hippocampal representations of self-motion and external cues may therefore contribute to path integration as well as spatial memory processing.

Location and head direction representation in the dorsal striatum of rats

The activity of dorsal striatal location and head direction neurons were recorded as rats performed a hippocampal-dependent spatial working memory task. Relative to previous descriptions of hippocampal fields, striatal fields appeared more dependent on the visual environment in which the maze was performed. Striatal head direction correlates were also shown to be dependent upon the visual context in a lit environment: The directional preferences rotated with the rotation of distal visual cue, and maze or rat rotations had no effect. However, when animals performed the maze in darkness, idiothetic information gained greater control over head direction preferences: Passive movement of the rat in darkness (but not in light) disrupted directional firing. During both light and dark trials, the same head direction preferences were observed. A special contribution of the dorsal striatum to navigation may be to facilitate an animal’s ability to switch between navigational strategies, thereby maintaining behavioral constancy in changing environments.

Superior colliculus and active navigation: Role of visual and non‐visual cues in controlling cellular representations of space

To begin investigation of the contribution of the superior colliculus to unrestrained navigation, the nature of behavioral representation by individual neurons was identified as rats performed a spatial memory task. Similar to what has been observed for hippocampus, many superior collicular cells showed elevated firing as animals traversed particular locations on the maze, and also during directional movement. However, when compared to hippocampal place fields, superior collicular location fields were found to be more broad and did not exhibit mnemonic properties. Organism‐centered spatial coding was illustrated by other neurons that discharged preferentially during right or left turns made by the animal on the maze, or after lateralized sensory presentation of somatosensory, visual, or auditory stimuli. Nonspatial movement‐related neurons increased or decreased firing when animals engaged in specific behaviors on the maze regardless of location or direction of movement. Manipulations of the visual environment showed that many, but not all, spatial cells were dependent on visual information. The majority of movement‐related cells, however, did not require visual information to establish or maintain the correlates. Several superior collicular cells fired in response to multiple maze behaviors; in some of these cases a dissociation of visual sensitivity to one component of the behavioral correlate, but not the other, could be achieved for a single cell. This suggests that multiple modalities influence the activity of single neurons in superior colliculus of behaving rats. Similarly, several sensory‐related cells showed dramatic increases in firing rate during the presentation of multisensory stimuli compared to the unimodal stimuli. These data reveal for the first time how previous findings of sensory/motor representation by the superior colliculus of restrained/anesthetized animals might be manifested in freely behaving rats performing a navigational task. Furthermore, the findings of both visually dependent and visually independent spatial coding suggest that superior colliculus may be involved in sending visual information for establishing spatial representations in efferent structures and for directing spatially‐guided movements. Hippocampus 1998;8:340–372.