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S J Mizumori

Publications and source records attributed to S J Mizumori.

At least 19 recordsLinked to original sources

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.

Amygdala↗

Temporary inactivation of the retrosplenial cortex causes a transient reorganization of spatial coding in the hippocampus.

The ability to navigate accurately is dependent on the integration of visual and movement-related cues. Navigation based on metrics derived from movement is referred to as path integration. Recent theories of navigation have suggested that posterior cortical areas, the retrosplenial and posterior parietal cortex, are involved in path integration during navigation. In support of this hypothesis, we have found previously that temporary inactivation of retrosplenial cortex results in dark-selective impairments on the radial maze (Cooper and Mizumori, 1999). To understand further the role of the retrosplenial cortex in navigation, we combined temporary inactivation of retrosplenial cortex with recording of complex spike cells in the hippocampus. Thus, behavioral performance during spatial memory testing could be compared with place-field responses before, and during, inactivation of retrosplenial cortex. In the first experiment, behavioral results confirmed that inactivation of retrosplenial cortex only impairs radial maze performance in darkness when animals are at asymptote levels of performance. A second experiment revealed that retrosplenial cortex inactivation impaired spatial learning during initial light training. In both experiments, the normal location of hippocampal "place fields" was changed by temporary inactivation of retrosplenial cortex, whereas other electrophysiological properties of the cells were not affected. The changes in place coding occurred in the presence, and absence, of behavioral impairments. We suggest that the retrosplenial cortex provides mnemonic spatial information for updating location codes in the hippocampus, thereby facilitating accurate path integration. In this way, the retrosplenial cortex and hippocampus may be part of an interactive neural system that mediates navigation.

Action Potentials↗

Dorsal striatal head direction and hippocampal place representations during spatial navigation.

Several theories of basal ganglia function describe a striatal contribution to learning that is independent of hippocampal function. This study examined the question of whether the striatum should be regarded as functioning independently of or acting in concert with limbic structures. Dorsal striatal head direction cells and hippocampal place cells were recorded in parallel while rats performed a hippocampal-dependent radial maze task. Changes in the directional preference of head direction cells and the location of place fields were compared following alterations of the sensory environment. When familiar visual cues were presented in new spatial arrangements, or when new visual cues were placed in a familiar environment, rotations of directional preferences were consistent with the mean place-field response. When familiar visual and nonvisual cues were presented in conflict, or when rats were exposed to novel environments, the responses of the two cell types were inconsistent relative to each other. This pattern suggests that current perceptions and expectations of familiar spatial contexts may dynamically modulate the relationship between hippocampus and dorsal striatum.

Animals↗

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.

Animals↗

Directing place representation in the hippocampus.

Theoretical models of rodent navigation consider location information and directional heading to be essential. Indeed, the existence of location-selective 'place cells' and orientation-selective 'head direction cells' is well documented. Different models suggest different forms of interaction between information about location and heading direction. However, until recently, there were no clear empirical data that could be used to distinguish the different models in terms of the nature of the integration of location and directional heading information. Recently, Leutgeb et al. provided evidence that head direction and place signals coexist within the CA1 region of hippocampus, and that the head direction signals are likely to be generated by a subpopulation of interneurons. This finding opens up new possibilities for clarifying current models and for developing biologically plausible theories of synaptic interactions between location and head direction codes. In this paper, we first present the issue concerning the nature of the interaction between location and head direction signals, followed by a selective review of place and head direction cell research. The finding of Leutgeb et al. is then summarized, and its implications for current models are discussed. Finally, a view is presented that considers place fields to be a product not only of (external and internal) sensory input, but also of non-spatial variables such as motivation and responses. The finding of Leutgeb et al. and many earlier anatomical studies suggest that hippocampal head direction, motivation and response information may be represented by the interneuron population. Thus, these factors may have strong impact on the location codes of hippocampal pyramidal neurons. Their influence may further define the behavioral context of the current spatial environment.

Animals↗

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.

Animals↗

Excitotoxic septal lesions result in spatial memory deficits and altered flexibility of hippocampal single-unit representations.

The septal nuclei are reciprocally connected with the hippocampal formation and contribute importantly to spatial and memory processing. Using excitotoxic lesions of the septal area, we investigated whether neurodegeneration in subcortical projections to hippocampus can compromise flexible information processing by hippocampal single units. In agreement with the mild effects of excitotoxic septal lesions on hippocampal physiology compared with fimbria-fornix lesions and septal inactivation, we observed limited lesion effects on single-unit activity. The location specificity of hippocampal complex spike cells remained unchanged, but a less reliable location-dependent discharge was observed in experimental animals with a pronounced postoperative working memory deficit. Testing in the absence of ambient illumination and in a new environment revealed that the spatial correlates of complex spike cells in lesioned animals may rely on a more limited set of sensory cues. Altered sensory cues resulted in a significantly different response pattern between the control and lesion group in the new environment, a situation that normally results in place field reorganization. Such a group difference was not observed during dark testing, a condition in which place field reorganization is less prominent. A contribution of hippocampal interneurons to the observed alterations in the spatial properties of the principal cells was suggested by decreased theta modulation in the lesioned group. Because excitotoxic lesions result in memory deficits that resemble age-related memory problems in the absence of age-related degenerative processes, we suggest that septal neurodegeneration could directly contribute to those behavioral changes with advanced age that correlate with functional alterations in the hippocampal formation.

Action Potentials↗

Retrosplenial cortex inactivation selectively impairs navigation in darkness.

There is an emerging consensus that retrosplenial and posterior parietal cortex importantly contribute to navigation. Several theories of navigation have argued that these cortical areas, particularly retrosplenial cortex, are involved in path integration. In an effort to characterize the role of retrosplenial cortex in active navigation, the effects of temporary inactivation of retrosplenial cortex on spatial memory performance were evaluated in light and dark testing conditions. Inactivation of retrosplenial cortex selectively resulted in behavioral impairments when animals were tested in darkness. These data support the hypothesis that retrosplenial cortex contributes to navigation in darkness, perhaps by providing mnemonic associations of the visual and nonvisual environment that can be used to correct for cumulative errors that occur during path integration.

Animals↗

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.

Animals↗

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.

Animals↗

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.

Amygdala↗

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.

Aging↗

Spatial- and locomotion-related neural representation in rat hippocampus following long-term survival from ischemia.

Spatial and locomotion-related behavioral correlates of hippocampal cell discharge were compared between ischemic and sham-control rats performing a spatial maze. Ischemic rats showed impaired choice accuracy during maze acquisition, but not during asymptote performance. Single-unit correlates during asymptote performance revealed enhanced spatial selectivity of CA2/3 complex-spike cells coincident with attenuated place-specific firing by hilar complex-spike or subicular cells. Responsivity to locomotion state by stratum granulosum interneurons was exaggerated, and locomotion-induced changes in firing of hilar and subicular interneurons was reduced. Ischemic rats showed recovered spatial learning abilities as evidenced by the fact that acquisition of the spatial task in a second environment was not impaired. Because representational reorganization was also observed in ischemic, maze-naive rats, brain injury per se appears to change information coding schemes.

Animals↗

Reversible inactivation of the lateral dorsal thalamus disrupts hippocampal place representation and impairs spatial learning.

Place-specific discharge of hippocampal cells was monitored while rats performed daily 15 trials of a spatial memory task. During the intertrial interval between trials 5 and 6, the lateral dorsal nucleus of the thalamus (LDN) was reversibly inactivated. Choice accuracy on the maze became impaired, and many hippocampal place fields became disrupted. These data support the proposition that the LDN passes onto hippocampus important (spatial) information that is used for accurate maze navigation.

Animals↗

Spatial, movement- and reward-sensitive discharge by medial ventral striatum neurons of rats.

Previous behavioral and acute electrophysiological data have lead researchers to speculate that the nucleus accumbens integrates limbic, reward and motor information. The present study examined the behavioral correlates to single unit activity of the nucleus accumbens and surrounding ventral striatum as a means of evaluating the integrative functioning of this region in an awake animal. Medial ventral striatum (mVS) activity was recorded as rats completed multiple trials on an eight arm radial maze. Neuronal activity was found to correlate with spatial, reward- and movement-related behavioral conditions. While the majority of cells demonstrated correlates of a single type (i.e. either spatial or reward correlates), 6 cells encoded multiple correlates of different types (i.e. spatial and reward correlates). The data suggests that this integrative process can be active both at the level of the individual neuron, and at the structural level. These results are consistent with the hypothesis that the mVS integrates spatial and reward-related information, which in turn influences voluntary motor output structures in order to achieve accurate navigational behavior.

Animals↗

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 animal's 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.

Animals↗

Medial septal modulation of entorhinal single unit activity in anesthetized and freely moving rats.

Reversible inactivation of the medial septal area results in a spatial memory impairment and selective disruption of hilar/CA3, but not CA1, location-specific discharge. The present study examined the possibility that such septal deafferentation produces effects on hippocampal function by altering physiological properties of the primary input and output structures for hippocampus, the entorhinal cortex and the subiculum, respectively. Single unit activity of hippocampal, entorhinal, and subicular cells was recorded before, during, and after septal injection of lidocaine in anesthetized rats. When compared to hippocampal cells, relatively few subicular and entorhinal cells showed a change in mean firing rate following septal inactivation. Entorhinal unit responses to septal inactivation (via tetracaine injection) were also examined in freely moving rats performing a spatial maze task. About one-third of entorhinal cells showed enhanced or reduced firing rates of 40% or more. Also, the spatial distribution of cells found in the superficial, but not deep, entorhinal layers became less clear following septal inactivation. Together, these data are consistent with the hypothesis that manipulation of the medial septum affects hippocampal function via its septosubicular and septo-entorhinal projections in addition to the more direct septohippocampal pathway. Since entorhinal cortical function was affected by tetracaine injection into the septum, it does not appear that direct entorhinal-CA1 afferents were primarily responsible for the maintenance of CA1 location-specific neural activity in previous septal inactivation experiments. Rather, these data are consistent with the hypothesis that the persistence of CA1 place fields was accomplished by intrahippocampal neural network operations.

Afferent Pathways↗