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    • br Spatial working memory is GluR A dependent The radial

    2022-08-02


    Spatial working memory is GluR-A-dependent The radial maze task also allowed us to study hippocampus-dependent spatial working memory. On spatial working memory tasks, the correct spatial response that the animal must make varies from trial to trial and is dependent on some conditional, trial-specific information that is relevant to that particular trial. The idea of distinct working memory and reference memory systems was first proposed by Honig (1978), and later elaborated upon by Olton et al. (1979). It is also worth pointing out, however, that the term ‘working memory’ has been used to reflect different processes by different researchers. For example, to many, and in particular researchers working with primates, working memory is a term often used to refer to a short-term, on-line memory supported by IFN-gamma, murine recombinant structures (Goldman-Rakic, 1987). In the present context, however, we use the term to refer to a flexible memory system in which conditional, trial-specific information is used to select between response options that are variably correct or incorrect. The performance on spatial working memory tasks is extremely sensitive to hippocampal lesions (Olton et al., 1979). Once the animals had learned which radial maze arms were baited and which never baited, then the working memory component of the task was introduced (Schmitt et al., 2003). Food rewards were not replaced within a trial and the mice were now allowed to re-enter arms as often as they wished. So now the animals needed to keep track of which arms they had already visited on that particular trial for efficient performance. If an animal entered an arm that was normally baited, but which it had already entered on that trial (and had already received the milk reward), then that was scored as a working memory error. In addition, reference memory errors (entries into never-baited arms) were scored as before. GluR-A−/− mice were less able to keep track of which arms they have already visited on a particular trial, and they made numerous working memory errors in which they re-visited arms that were no longer baited, whereas the wild-type mice made virtually none of these kinds of errors (Fig. 4). Importantly, despite the working memory impairment, the GluR-A−/− mice were, however, still able to remember which arms were never baited. They showed intact reference memory performance on the very same trials during which they were making numerous working memory-type errors. This, therefore, provides a within-subject and within-task demonstration of impaired hippocampus-dependent spatial working memory but spared hippocampus-dependent spatial reference memory performance. As both reference and working memory components of the radial maze task involve using the same set of spatial cues, and presumably have the same sensorimotor and motivational demands, this dissociation argues very strongly for a specific role for GluR-A in hippocampus-dependent spatial working memory processes, and against an account based on a non-specific disruption of maze performance per se.
    Spatial working memory on the T-maze Spatial working memory performance can also be studied using a spatial non-matching to place or rewarded alternation task on a simple three-arm maze such as an elevated T-maze or Y-maze. As with the spatial working memory component of the radial maze task, the relationship between the spatial cues and the goal location (i.e. the milk reward) changes from trial to trial. The animal receives some information on a sample trial which acts as conditional information that the animal must then use to select the appropriate response on the subsequent choice trial. The conditional information is only relevant on that trial. On the T-maze-rewarded alternation task the rat or mouse is first forced into one arm of the maze during a sample run where it then receives a reward (Fig. 5). The mouse is then returned to the beginning of the start arm and is given a free choice of either arm. The mouse is rewarded for choosing the previously unvisited arm (i.e. for alternating). Many trials are run over a period of time with the goal arm visited on the sample run designated by a pseudorandom sequence. Successful performance on this task also depends on an intact hippocampus, and, in particular, on the dorsal hippocampus (Rawlins and Olton, 1982; Hock and Bunsey, 1998; Bannerman et al., 1999). Both mice and rats with complete and dorsal hippocampal lesions are dramatically impaired on this task and display chance levels of performance (50%) (Bannerman et al., 2002; Deacon et al., 2002) (Fig. 5). Similarly, the GluR-A knockout mice exhibit a devastating and lasting impairment. The performance of the knockout mice, like rats or mice with hippocampal lesions, remains steadfast at chance even after many trials (Reisel et al., 2002). The GluR-A−/− mice are unable to discriminate between the unvisited and visited arm from the previous sample trial (Fig. 5).