Long-term working memory in the rat: Effects of hippocampally applied anisomycin.

The extent to which protein synthesis is involved in working memory was investigated with the protein synthesis inhibitor anisomycin (ANI). Male albino and Long-Evans rats were trained to perform accurately on a 12-arm radial maze when delays of 240 min were interposed between Choice 6 and Choice 7. Bilateral hippocampal cannulas were then implanted. Accuracy on Choices 7–22 was studied when ANI (80 μg/μl) or saline was injected either 30 min before Choice 1 or 5–20 min after Choice 6 in Exp I. Pretrial injection of ANI significantly impaired performance following the 240-min delay, whereas ANI injected during the delay had no such effect. In Exps II and III, the ANI-induced amnesia was replicated, and the temporal course of development of the amnesia was determined. Pretrial administration of ANI did not significantly affect retention after a 2-min delay but produced amnesia after delays of 15 min or longer. Data suggest that protein synthesis is important for the formation of temporary memories, provided the retention interval is long enough. It is suggested that working memory includes both short- and long-term components. Protein synthesis appears to be important for formation of the long-term component, but not the short-term component, of working memory. (31 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short- and long-term components of working memory in the rat.

In Experiment 1 of this report, we examined the neuropharmacological nature of short-term working memory of rats trained to retrieve food from all arms of a 12-arm radial maze. Delay intervals of varying length were placed between Choices 6 and 7. Lanthanum (LaCl?) and glutamate (GLU) injected bilaterally into the hippocampus effectively impaired retention over short delay intervals, which suggests a possible role for calcium and/or potassium and for glutamate in working memory. However, another equally likely explanation for the amnesic effects of LaCl? and GLU is that these drugs impaired reference memory. To test more directly the hypothesis that LaCl?, GLU, or ANI might differentially affect working and reference memory, we tested the effects of these drugs on performance of rats trained to retrieve food from only 8 arms of the 12-arm maze in Experiment 2. The remaining 4 arms were never baited, in order to test reference memory function. We predicted that rats would make errors only in baited arms (i.e., errors of working memory). Instead, results of Experiment 2 showed that LaCl?, GLU, or ANI injection produced errors in unbaited arms even before a 120-min delay. If rats were injected with LaCl? or GLU, baited-arm errors were observed only after the delay period. No impairment of performance on baited arms were observed after injection of ANI. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

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 were 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Role of the dorsomedial striatum in behavioral flexibility for response and visual cue discrimination learning.

These experiments examined the effects of dorsomedial striatal inactivation on the acquisition of a response and visual cue discrimination task, as well as a shift from a response to a visual cue discrimination, and vice versa. In Experiment 1, rats were tested on the response discrimination task followed by the visual cue discrimination task. In Experiment 2, the testing order was reversed. Infusions of 2% tetracaine did not impair acquisition of the response or visual cue discrimination but impaired performance when shifting from a response to a visual cue discrimination, and vice versa. Analysis of the errors revealed that the deficit was not due to perseveration of the previously learned strategy, but to an inability to maintain the new strategy. These results contrast with findings indicating that prelimbic inactivation impairs behavioral flexibility due to perseveration of a previously learned strategy. Thus, specific circuits in the prefrontal cortex and striatum may interact to enable behavioral flexibility, but each region may contribute to distinct processes that facilitate strategy switching. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Measuring information spatial densities.

A novel definition of the stimulus-specific information is presented, which is particularly useful when the stimuli constitute a continuous and metric set, as, for example, position in space. The approach allows one to build the spatial information distribution of a given neural response. The method is applied to the investigation of putative differences in the coding of position in hippocampus and lateral septum.     

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 the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context-dependent modulation by D? receptors: Differential effects in hippocampus and striatum.

Place-specific firing by hippocampal and striatal neurons was recorded simultaneously following injection of a D? receptor antagonist (SCH23390) and during spatial working memory task performance. SCH23390-induced changes in unit responses were observed during light and dark test conditions. Although hippocampal place field locations were altered by the contextual change, the reliability and specificity of place fields was disrupted only by combining D? antagonism and a change in context. Striatal place field locations were reorganized after either contextual change or D? antagonism, without altering place field reliability and specificity. Disrupted velocity encoding by place cells in both regions was induced by darkness, whereas greater stability in acceleration encoding followed removal of D? receptor activity. Dopamine may differentially regulate hippocampal context learning and striatum-based predictive codes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context-Dependent Reorganization of Spatial and Movement Representations by Simultaneously Recorded Hippocampal and Striatal Neurons During Performance of Allocentric and Egocentric Tasks.

Hippocampal and striatal place- and movement-correlated cell firing was recorded as rats performed place or response tasks in a familiar environment, and then after cue manipulation. In a familiar environment, place field properties did not differ across brain structures or task conditions. Movement correlates were stronger during place task performance only in hippocampal neurons. After cue manipulations, place- and movement-sensitive hippocampal and striatal neurons changed their correlate strength, regardless of behavioral strategy. Thus, for both structures, place-correlated cells may encode spatial context information, whereas movement-correlated cells may represent both egocentric movement and learned behavioral responses. The striking overall similarity between hippocampal and striatal neural responses to context manipulation (regardless of strategy) suggests that these structures operate continuously, and in parallel, during multiple forms of learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)