David S. Olton

Hippocampus, space, and memory

We examine two different descriptions of the behavioral functions of the hippocampal system. One emphasizes spatially organized behaviors, especially those using cognitive maps. The other emphasizes memory, particularly working memory, a short-term memory that requires iexible stimulus-response associations and is highly susceptible to interference. The predictive value of the spatial and memory descriptions were evaluated by testing rats with damage to the hippocampal system in a series of experiments, independently manipulating the spatial and memory characteristics of a behavioral task. No dissociations were found when the spatial characteristics of the stimuli to be remembered were changed; lesions produced a similar deficit in both spatial and nonspatial test procedures, indicating that the hippocampus was similarly involved regardless of the spatial nature of the task. In contrast, a marked dissociation was found when the memory requirements were altered. Rats with lesions were able to perform accurately in tasks that could be solved exclusively on the basis of reference memory. They performed at chance levels and showed no signs of recovery even with extensive postoperative training in tasks that required working memory. In one experiment all the characteristics of the reference memory and working memory procedures were identical except the type of memory required. Consequently, the behavioral dissociation cannot be explained by differences in attention, motivation, response inhibition, or the type of stimuli to be remembered. As a result of these experiments we propose that the hippocampus is selectively involved in behaviors that require working memory, irrespective of the type of material (spatial or nonspatial) that is to be processed by that memory.

Spatial memory and hippocampal function

Abstract Rats with damage to the fimbria-fornix were tested for the post-operative retention of a preoperatively learned discrimination on a radial arm maze. The maze contained two sets of arms. One set, which never had food on them, comprised the “reference memory” task. The correct response on every approach to each arm in this unbaited set was to refrain from entering it. A second set of arms, each of which had one pellet of food on it at the beginning of a test, comprised the “working memory” task. The correct response to each of the arms in this baited set changed during a test. On the first approach to each of them, the correct response was to run down the arm and obtain the food there; on all subsequent approaches the correct response was to refrain from running down the arm because the food was no longer available. At the end of postoperative testing, performance on the reference memory task was normal, while performance on the working memory task was severely impaired by large lesions and slightly impaired by small ones. Rats with the most complete fimbria-fornix lesions showed no signs of improvement in working memory. This behavioural dissociation suggests a differential involvement of the hippocampus in working memory as compared to reference memory.

Hippocampal connections and spatial discrimination

Rats were tested in a new spatial discrimination procedure which measured working memory. Following preoperative testing, lesions were placed to disrupt each of the major extrinsic fiber connections of the hippocampal formation. Destruction of the entorhinal area, body of the fimbria-fornix anterior to hippocampus, septum, or postcommisural fornix produced a severe and consistent impairment in performance. Analysis of error patterns indicated that when animals with limbic lesions made errors, they were likely to make these errors in the same sequence as the original choices. These data support the hypothesis that the hippocampus has an important role in the processing of information about spatial location, and that normal performance on this task requires an intact hippocampal circuitry.

Hippocampus, time, and memory.

Five experiments were conducted to determine the effects of hippocampal damage on timing and the memory for temporal events. In Experiments 1-3, rats were trained to discriminate between auditory signals that differed in both duration (2 or 8 s) and rate (2 or 16 cycles/s). Half of the rats were trained to discriminate duration, and half were trained to discriminate rate. After rats acquired the relevant discrimination, signals with intermediate durations and rates were presented to obtain psychophysical functions that related signal duration and/or rate to response choice. Rats then received either lesions of the fimbria-fornix or control operations. Postoperatively, the accuracy of duration and rate discriminations as measured by the difference limen (DL) was unaffected by the lesion, but the point of subjective equality (PSE) was shifted to a shorter duration and a slower rate by the lesion in Experiment 1. Both rats with lesions and rats with control operations showed cross-modal transfer of duration and rate from the auditory signals used in training to visual signals used in testing in Experiment 2. A 5-s delay was imposed between the end of a signal and the opportunity to respond in Experiment 3. The delay served as a retention interval for the rats trained in the rate discrimination, and the rats with fimbria-fornix lesions were selectively impaired by the addition of the delay as measured by an increase in the DL. The delay did not serve as a retention interval for rats trained in the duration discrimination because they were able to continue timing through the delay. A peak procedure was employed in Experiment 4. The maximum response rate of control rats was approximately at the time of scheduled reinforcement (20 s), but the maximum response rate of rats with fimbria-fornix lesions was reliably earlier than the time of scheduled reinforcement. When a 5-s gap was imposed in the signal, control rats summed the signal durations before and after the gap, whereas rats with fimbria-fornix lesions showed no retention of the signal duration prior to the gap. Experiment 5 continued the testing of the rats used in Experiments 1-4 and showed that rats with lesions had an impairment in a test of spatial working memory in an eight-arm radial maze. Taken together, these results demonstrate that a fimbria-fornix lesion interferes with temporal and spatial working memory, reduces the remembered time of reinforcement stored in reference memory, and has no effect on the animals sensitivity to stimulus duration.

Spatial memory and radial arm maze performance of rats

Abstract Rats were tested on an elevated radial maze for their ability to choose each of 17 different arms once without repeating any choices. The first experiment indicated that the animals performed well, choosing an average of more than 14 different arms in the first 17 choices. Subsequent experiments demonstrated that: (a) response patterns, general algorithms, or intramaze markings were not necessary for correct choices: (b) there was interference among choices within a test so that the probability of a correct response decreased as the number of choices increased; (c) there was no serial-order effect (primacy or recency); (d) animals tested in a procedure which did not require prior shaping showed no evidence of a general predisposition not to repeat choices. The results are discussed in terms of capacity, accuracy, and other characteristics of working spatial memory.

Age-related spatial reference and working memory deficits assessed in the water maze

Aged rats have spatial memory deficits relative to young rats. The extent of these deficits in intermediate-aged rats is not well established. The present study examined the pattern of age-related changes in spatial reference and working memory in four ages of Fischer-344 rats. Place discrimination (PD) in the Morris water maze measured spatial reference memory. Repeated acquisition (RA), a discrimination in which the escape platform location varied from session to session, measured spatial working memory. Fischer-344 rats, 4 months, 11 months, 17 months, and 24 months of age, were tested. Compared to 4-month-olds, 24-month-olds were significantly impaired on all six PD measures of performance, 17 months were significantly impaired on five PD measures, and 11 months were significantly impaired on only one PD measure. Only 24-month-olds had a significant working memory impairment in RA relative to 4 months. Reference and working memory measures were distinct as assessed by a principal components analysis. The results indicate a nonlinear age-related spatial memory decline in Fischer-344 rats from 4 to 24 months of age.

Neuroanatomical bases of spatial memory.

Although many brain areas have been implicated in spatial memory processes, recent investigations have focused on the hippocampal formation. The present experiment was designed to determine the relative importance of the hippocampal system as compared to the amygdala, the caudate nucleus, or the frontal cortex. Groups of rats were trained to perform on an eight-arm radial maze and then given lesions in one of these brain areas. The post-operative performance of rats with lesions in the fimbria-fornix was never significantly greater than that expected by chance. In contrast, the performance of rats with lesions in the amygdala, the caudate nucleus or the sucal frontal cortex was not significantly different from that of controls. The performance of rats with lesions in the medial frontal cortex was substantially impaired relative to that of the controls during the first few post-operative test sessions, but improved so that by the end of testing the rats were performing as well as were controls. The recovery of function by the rats with lesions in the medial frontal cortex was a function of experience testing on the maze and not simply the passage of time following surgery. Thus, only rats with functional hippocampal systems were able to perform the maze task accurately while thos rats with lesions in the hippocampal system were not.

Spatial correlates of hippocampal unit activity.

Abstract Electrical activity of units in the hippocampus was recorded from freely behaving rats as they explored a spatial maze. The maze had eight arms, each of which radiated from the center platform-like spokes of a wheel. Of 31 hippocampal “complex spike” units, 27 had strong “spatial correlates” as defined by the following conjoint criteria: (i) the mean rate of activity on at least one of the eight arms was different from the overall grand mean by at least three standard errors of the mean; (ii) the mean rate of activity on each visit to an arm was significantly different from the overall grand mean by a Sign test. The first criterion tests the magnitude of the rate of change associated with a particular spatial location and the second criterion tests the reliability of this rate change. Spatial correlates were reflected by both an increase in rate (“on” field) and a decrease in rate (“off” field), and ranged from discrete fields which were restricted to a single arm to broad fields which encompassed several arms. These data provide strong support for the hypothesis that the hippocampus is involved in the processing of spatial information.

Memory impairments following basal forebrain lesions.

The functional contribution of the nucleus basalis magnocellularis (NBM) and medial septal area (MSA) to memory was evaluated in 4 behavioral tasks. The tasks were postoperative acquisition of a win-stay spatial discrimination in a T-maze, a win-shift spatial discrimination on a radial arm maze, active avoidance in a shuttle box, and passive avoidance in a shuttle box. Bilateral lesions were made by injecting ibotenic acid (IBO) into the NBM or MSA. Control rats received operations in which no neurotoxin was injected. When compared to controls, rats with lesions in either the NBM or MSA had significantly impaired choice accuracy in the T-maze and radial maze tasks, took significantly fewer trials to reach criterion in the acquisition, but not the retention of an active avoidance task, and significantly more trials to reach criterion in the passive avoidance task. The results show that equivalent behavioral changes are obtained from lesions in the NBM and MSA in tasks that vary in their type of motivation, reinforcement, response-reinforcement contingency, and response. These behavioral changes suggest that the NBM and MSA may both be involved in memory.

ATTENTION AND THE FRONTAL CORTEX AS EXAMINED BY SIMULTANEOUS TEMPORAL PROCESSING

The brain mechanisms involved in attention and memory were examined by testing rats in temporal discriminations designed to emphasize these cognitive processes. Normal rats were able to time each of two stimuli whether they were presented alone or together. Rats with lesions of the frontal cortex (FC) or nucleus basalis magnocellularis (NBM) were able to time each stimulus when it was presented alone, but not when it was presented together with another stimulus. Rather, these rats timed only the intruding stimulus and ignored the other, demonstrating a failure of divided attention. Rats with lesions of the fimbria-fornix (FF) or medial septal area (MSA) performed the divided attention task normally, but failed to remember the duration of a stimulus that had been terminated temporarily earlier in the trial, demonstrating a failure of working memory. These results provide another informative dissociation between the functions of the frontal and hippocampal systems, emphasizing frontal involvement in attention, and hippocampal involvement in working memory.