The contribution of anterior and posterior cingulate cortical areas to spatial learning and memory was examined in 4 experiments using the place-navigation task. Rats with complete bilateral cingulate cortex aspiration or aspiration of posterior cingulate cortex (area 29) alone could not swim directly to a hidden platform located in a fixed place. When animals with these lesions were tested for 40 d in a place-alternation task in which they received 16 daily trials with the platform placed in a new location each day, they did not show reliable improvement in place navigation. The inability to swim to changing locations or to a single location was not overcome by preoperative training in these tasks. Rats with anterior cingulate cortex aspirations showed a less severe impairment in both tasks and, with more training than is necessary for control rats, they acquired near-normal place-navigation accuracy. Rats with complete cingulate cortex aspiration were almost as accurate as control rats in learning to swim to a visible platform. The results imply that posterior cingulate areas play an essential role in the use of topographical information, probably by transmitting and elaborating information passing between the hippocampal system and neocortical association areas.

Some theories of hippocampal formation function postulate that it is involved in using the relationships between distal cues for spatial navigation. That rats with damage to the hippocampal formation are impaired in learning place responses of escaping to a platform hidden just below the surface of the water of a swimming pool, supports this view. Using rats with fimbria-fornix (FF) lesions, we examined whether their impairment is related to an inability to learn how to reach the platform as opposed to learning its location. In a first experiment, the FF rats were impaired in learning to swim to a hidden platform but could swim to a visible platform. In a second experiment, after being pretrained to swim to a visible platform, the FF rats swam to, paused, and searched the vicinity of the platform's previous location when it was removed. This finding showed that the FF rats expected to find the platform at that location. Additional tests confirmed that they had learned a place response. Despite having acquired a place response, they still could not acquire new place responses when only the hidden platform training procedure was used. Thus, these results in dissociating the processes of "getting there" and "knowing where" suggest that the FF rats' impairment may be in some process of motoric control, such as path integration, rather than in learning the location of the platform in relation to ambient cues. The results are discussed in relation to relevant theories of hippocampal function.

It is well known that ischemia causes neuronal necrosis in selectively vulnerable sectors of the hippocampus. Since the hippocampus is involved in spatial navigation, learning, and memory, selective deficits in these areas may arise from ischemic brain damage. The objective of this study was to test whether a minimal ischemic insult, producing selective neuronal necrosis restricted to only a portion of the CA1 pyramidal cells of the hippocampus, could produce a detectable spatial navigation deficit. Male Wistar rats received 9 min of forebrain ischemia induced by carotid clamping and hypotension or sham operation with exposure of the carotid arteries. The rats were allowed to recover and were tested on a simple place task, a place learning-set task, and a pattern discrimination task in swimming pools paradigms. Subsequently, the rats were perfusion-fixed and their entire brains subjected to quantitative histopathologic analysis. Although both ischemic and sham-operated groups learned the simple place task, the learning-set task revealed defects in spatial navigation, reflected as increased errors and latency in the performance of the ischemic rats. In the subsequent pattern discrimination task, the ischemic group was superior to the control group, which perseverated by attempting to use a place strategy to solve the discrimination. Quantitative neuropathology revealed neuronal necrosis in the ischemia group limited to 50% of the CA1 zone of the hippocampus. Extrahippocampal damage consisted of rare cortical neuronal necrosis in 2 of 6 animals.(ABSTRACT TRUNCATED AT 250 WORDS)

No abstract

We investigated the ability of postischemic insulin administration to modify the structural and neurobehavioral consequences of cerebral ischemia in rats. Forebrain ischemia was induced in fed rats by combining controlled systemic hypotension with bilateral carotid artery damping for IOV2 minutes. Following damp release, one group of five rats was given insulin (2 IU/kg s.c. b.i.d.) for 1 week. An ischemic-control group of six rats received no postischemic treatment. A sham-ischemia group of rats was used as a behavioral control. Throughout the recovery period until sacrifice, the drinking water of all rats was supplemented with 25% glucose. Rats were trained on two water maze place navigation tasks 1-2 months after ischemia. Escape latencies and swim patterns were recorded. Performance in the insulin-treated group was better than that in the ischemic-control group (p<0.05) on both tasks and did not differ significantly from that of the sham-ischemia group. Improvement in behavior correlated with a significant reduction in CA1 hippocampal necrosis in the insulin-treated group (p<0.05). Our findings demonstrate that postischemic treatment with insulin improves neurobehavioral performance in addition to lessening ischemic neuronal necrosis. (Stroke 1989;20:646-651)T reatment for cerebral ischemia should ideally reduce neurologic and cognitive dysfunction as well as preserve tissue morphology. Our recent finding that insulin-induced hypoglycemia following transient forebrain ischemia in rats significantly reduces structural brain damage 1 prompted us to investigate the long-term behavioral effect of reducing postischemic blood glucose levels. The CA1 sector of the hippocampus is susceptible to ischemic insult.2 Memory function in turn is highly susceptible to CA1 neuronal loss.3 -6 Cerebral ischemia can induce a persistent amnestic syndrome secondary to CA1 neuronal loss in rats 7 and humans.3 -8 -9 Using water maze-based place navigation tasks, we studied the effect of insulin administration on postischemic spatial learning dysfunction in rats. Received September 20, 1988; accepted November 30, 1988. Materials and MethodsThe ischemia model we used was based on that of Smith et al 10 and has been described. 1 Seventeen male Wistar rats (Charles River Breeding Centre, St. Constant, Canada) weighing 250-450 g, which had been allowed free access to food and water, were anesthetized with 4% halothane in 2:1 N 2 O: O 2 . The rats were then intubated and ventilated throughout the procedure with a Starling-type ventilator (Harvard, Edenbridge, England). The ventral tail artery was cannulated and connected to a Statham transducer (P50, Gould, Cleveland, Ohio) for continuous monitoring of mean arterial blood pressure (MABP). A Silastic catheter (Silastic tubing, Dow Corning, Midland, Michigan) was inserted into the right jugular vein and positioned with its tip in the inferior vena cava. The common carotid arteries were exposed and dissected free of the carotid sheaths and sympathetic chains. Subcutaneous unipolar parietal ...