Hiroshige Okaichi

On the role of hippocampal connections in the performance of place and cue tasks: comparisons with damage to hippocampus.

Behavioral changes following interruption of the main connections of hippocampus and closely related areas (entorhinal cortex, mammillary bodies, dentate gyrus) were determined and compared with findings of previous research that involved direct damage to hippocampus. By a within-subjects design, rats were trained to run in a radial maze with a procedure that involved two kinds of learning (place and cue) and two memory functions (working and reference memory). Rats with fimbria-fornix and entorhinal cortex lesions were impaired on both the place and the cue task. Specifically, the animals suffered a general impairment in working memory on both tasks but were impaired in reference memory only on the place task. Animals with lesions of the dentate gyrus and mammillary bodies were able to perform the complex place and cue tasks with minimal problems. In previous research it was found that direct damage to hippocampus (including all cell fields, alveus, fimbria) resulted in impaired performance only on the place task (Jarrard, 1983). Taken together, these findings indicate that interruption of hippocampal input/output pathways and/or damaging some closely related structures has a greater effect on the behaviors studied than does direct damage to hippocampus.

Long-term dietary restriction causes negative effects on cognitive functions in rats.

Long-term dietary restriction is reported to increase life span and improve age-related cognitive deficits. The present study shows that the restriction increases the life span of rats but decreases their cognitive ability. Thirty-two rats were divided into restricted and ad lib feeding groups at 2.5 months of age. The restricted rats were kept at a weight of 280g. The restricted rats were poor in performing the Morris water maze task at 7-12 months. At 17-18 months, they were poor in performing the delayed matching-to-place task. At 24-27 months, the surviving 13 restricted and 5 ad lib rats performed the spatial discrimination task. The restricted rats were also poor in performing this task. Injection of glucose prior to the discrimination task improved their performance to the level of the ad lib rats. These results suggest that dietary restriction is beneficial for longevity but has negative effects on the performance of cognitive tasks, and that the cause of the negative effects may be a reduced availability of glucose in the food-restricted aged rats.

Scopolamine impairs both working and reference memory in rats: a replication and extension.

Rats were trained to run in a spatial, radial maze for sucrose reward using a procedure that permitted determination of two memory functions [working memory (WM) and reference memory (RM)]. Injections of saline, 0.1, 0.4, and 0.8 mg/kg of scopolamine hydrobromide were administered using a Latin-square design; a single dose (0.4 mg/kg) of scopolamine methylbromide served as a control for peripheral drug effects. The smallest dose of scopolamine (0.1 mg/kg) had no measurable effect on performance, but as the dose was increased to 0.4 and 0.8 mg/kg there were increases in both WM and RM errors, in errors of omission, and increases in running time. These results support the view that the effects of scopolamine on performance in the radial maze is not specific for working memory, but rather the effects are more general in nature.

Synaptic plasticity preserved with arachidonic acid diet in aged rats

We examined whether synaptic plasticity was preserved in aged rats administered an arachidonic acid (AA) containing diet. Young male Fischer-344 rats (2 mo of age), and two groups of aged rats of the same strain (2 y of age) who consumed either a control diet or an AA ethyl ester-containing diet for at least 3 mo were used. In the Morris water maze task, aged rats on the AA diet had tendency to show better performance than aged rats on the control diet. Long-term potentiation induced by tetanic stimulation was recorded from a 300 microm thick hippocampal slice with a 36 multi-electrode-array positioned at the dendrites of CA1 pyramidal neurons. The degree of potentiation after 1 h in aged rats on the AA diet was comparable as that of young controls. Phospholipid analysis revealed that AA and docosahexaenoic acid were the major fatty acids in the hippocampus in aged rats. There was a correlation between the behavioral measure and the changes in excitatory postsynaptic potential slope and between the physiologic measure and the total amount of AA in hippocampus.

Choice behavior of hippocampectomized rats in the radial arm maze

Rats with hippocampal lesions (n = 16), sham-operated controls (n = 5), and unoperated controls (n = 8) were trained on place and cue tasks in an elevated radial arm maze. Hippocampallesioned rats had impaired working memory and impaired cognitive-map formation. The behavior of the hippocampals in choosing arms was different from that of the controls even immediately after training began. The hippocampals were not able to rapidly perceive the spatial requirements of the task and did not show the inherent stereotyped behavior employed by controls. Nonetheless, the hippocampals showed that they could learn problem-solving behavior as training progresses.

Arachidonic acid improves aged rats' spatial cognition

To examine the effects of arachidonic acid (AA) on age-related cognitive deficits, F-344 rats were administered with an AA-supplemented powder diet from 79 weeks of age (OA group). For comparison, we also used an age-matched control group of animals (OC group) that were fed with a non AA-supplemented powder diet. When the subjects reached 87 weeks old, they were trained for Morris water maze place and cue tasks. Escape latencies of the OA group on the place task were significantly shorter than those of the OC group in the latter half of training. The probe test showed that OA rats remembered the trained platform position significantly better than OC rats. In the cue task training, the OC group was significantly slower than the OA group at the beginning of training, but their performance soon matched with that of the OA group. Fatty acids in the hippocampi were measured after the behavioral testing. There was no difference in AA composition in hippocampal phospholipids between the OA and OC groups. However, regression analysis conducted on AA composition and place task performance showed a significant correlation between these two parameters. The present study suggests that AA administration to aged animals can alleviate age-related deficits in spatial cognition.

Learning behaviour in chronic vitamin E-deficient and-supplemented rats: radial arm maze learning and passive avoidance response

The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.

Functional cooperation between the hippocampal subregions and the medial septum in unreinforced and reinforced spatial memory tasks

Anatomical connections between the medial septum (MS) and hippocampus (Hipp) via the fimbria-fornix suggest that functional cooperation between these structures may be important for the acquisition and use of spatial reference memories. The present study examined the extent to which this was true for both an unreinforced learning task (object exploration task) and a reinforced learning task (Morris water maze task). In Experiment 1, we compared the performance of MS/Hipp contralateral- and MS/Hipp ipsilateral-lesioned rats. MS/Hipp contralateral-lesioned rats exhibited deficient performance in both the object exploration and Morris water maze tasks. In Experiment 2, we examined the task performance of MS/CA1 contralateral-, MS/CA1 ipsilateral-, MS/CA3 contralateral- and MS/CA3 ipsilateral-lesioned rats. Contralateral MS/CA3 and MS/CA1 lesions were respectively associated with deficient performance at the spatial recognition test and object recognition test in the object exploration task. None of the lesioned rats performed deficiently in the Morris water maze task. These results indicate the importance of spatial reference memory of a functional cooperation between the MS and Hipp as a whole, irrespective of reward contingency. In contrast, functional cooperation between the MS and each of CA1 and CA3 played an important role in the performance of the unreinforced voluntary task, but not in the reinforced task. Further, the functional cooperation of both MS/CA3 and MA/CA1 were important in the spatial reference memory with the unreinforced task.

Functional differentiation and cooperation among the hippocampal subregions in rats to effect spatial memory processes.

We investigated the roles of the hippocampal subregions and intrahippocampal networks in effecting spatial reference and working processes. The results showed that the dentate gyrus plays a key role in encoding both types of spatial memory. Lesions in the dentate gyrus caused severe impairment in the acquisition of the Morris water maze and delayed matching-to-place tasks as compared to those in the other hippocampal subregions (Exp. 1). Further, there was functional cooperation between CA3 and CA1 via the Schaffer collaterals and the hippocampal commissure in the performance of both types of spatial memory tasks. Among the rats with intact hippocampal commissure, those with both contralateral and ipsilateral CA1/CA3 lesions showed a similar performance (Exp. 2A); however, among the rats with transected hippocampal commissure, those with the contralateral CA1/CA3 lesions showed a more disruptive performance than the rats with the ipsilateral CA1/CA3 lesions (Exp. 2B). This study suggests that the hippocampus is the functional unit for spatial reference and working memory processes, including differential functions and functional cooperation among the hippocampal subregions.

Use of Win-Stay and Win-Shift Strategies in Place and Cue Tasks by Medial Caudate Putamen (MCPu) Lesioned Rats

This study investigated the behavioral function of the medial caudate putamen (MCPu) in the solving of maze tasks. MCPu lesioned rats (n = 35) and control rats (n = 35) were trained for the place or cue task (the four baited arms and four unbaited arms task) in an eight-arm radial maze, which requires the win-stay or the win-shift strategy. In Experiment 1, in which the place task was used, MCPu lesioned rats could learn the task in the win-shift condition, but not in the win-stay condition. MCPu lesioned rats made a lot of unbaited errors in the win-stay condition, as they persistently chose adjacent arms. Control rats could learn the tasks in both conditions. In Experiment 2, in which the cue task was used, MCPu lesioned rats and control rats could learn the tasks in both the win-stay and the win-shift conditions. If anything, the performance of MCPu rats was a little better than that of control rats in the win-stay condition. The results of these two experiments revealed that the MCPu was involved in solving the win-stay place task, but not the win-shift place, win-stay cue, and win-shift cue tasks. These findings suggest that the MCPu plays an important role in utilizing both spatial information and switching foraging strategies flexibly and efficiently, that is, processing complicated visuospatial cognition.