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Improvement on spatial tasks is observed during a late, postnatal developmental period (PND18 - PND24).  The purpose of the current work was 1) to determine whether the emergence of spatial-behavioral function was based on the ability to generate appropriate behavioral output; 2) to assess whether mossy fiber connectivity patterns preceded the emergence of spatial-behavioral function; 3) to explore functional changes in the hippocampus to determine whether activity in hippocampal networks occurred in a training-dependent or developmentally-dependent fashion.  To these ends, male, Long Evans rats were trained on a spatial water or dry maze task for one day (PND16, PND18 or PND20) then euthanized.  Training on these 2 tasks with opposing behavioral demands (swimming versus exploration) was hypothesized to control for behavioral topology.  Only at PND20 was there evidence of spatial-behavioral function for both tasks.  Examination of synaptophysin staining in the CA3 region (i.e., mossy fiber projections) revealed enhanced connectivity patterns that preceded the emergence of spatial behavior.  Analysis of c-Fos labeling (functional changes) revealed developmentally-dependent increases in c-Fos positive cells in the dentate gyrus, CA3 and CA1 regions whereas training-dependent increases were noted in the CA3 and CA1 regions for the water-maze trained groups.  Results suggest that changes in mossy fiber connectivity in association with enhanced hippocampal functioning precede the emergence of spatial behavior observed at PND20.  The combination of neuroanatomical and behavioural results confirms the hypothesis that this time represents a sensitive period for hippocampal development and modification and the emergence of spatial/ cognitive function.

We review evidence from experiments conducted in our laboratory on retrograde amnesia in rats with damage to the hippocampal formation. In a new experiment reported here, we show that N-methyl-D-aspartate (NMDA)-induced hippocampal damage produced retrograde amnesia for both hidden platform and two-choice visible platform discriminations in the Morris water task. For both problems there was a significant trend for longer training-surgery intervals to be associated with worse retention performance. Little support is offered by our work for the concept that there is a process involving hippocampal-dependent consolidation of memories in extrahippocampal permanent storage sites. Long-term memory consolidation may take place within the hippocampus. The hippocampus may be involved permanently in storage and/or retrieval of a variety of relational and nonrelational memories if it was intact at the time of learning, even involving information which is definitely not affected in anterograde amnesia after hippocampal damage.

Rats were tested on an allocentric-spatial working-memory task--delayed matching-to-place (DMTP) in a water maze--before and after either pyrithiamine-induced thiamine deficiency (PTD) or electrolytic lesions of the lateral internal medullary laminae (IML), an area damaged by PTD. DMTP trials consisted of paired swims, with the escape platform in a new location on each trial. PTD rats were impaired at retention delays of 300 s, but not at delays of 4 or 60 s. Rats with IML lesions performed normally at all delays. Both groups displayed normal retention of object-discrimination problems that they had learned at different intervals before treatment (5 weeks, 3 weeks, and 1 week). The results suggest that PTD causes delay-dependent deficits of allocentric spatial working memory and that damage outside the IML is probably responsible. Neither PTD-induced diencephalic damage nor restricted IML lesions appear to produce a global retrograde amnesia.

Two experiments compared the effects of bilateral lesions of the hippocampal formation (HPC) or perirhinal cortex (PRh) on rats' performance of an allocentric spatial working memory task--delayed matching-to-place (DMTP) in a water maze. DMTP trials consisted of paired swims, and the hidden platform was moved to a new location on each trial. Performance was assessed with intervals between the first and second swim (i.e., retention delays) of 4, 30, 120, and 300 s. The rats received extensive presurgery training in Experiment 1 and no presurgery training in Experiment 2. In both experiments, rats with HPC lesions displayed DMTP deficits at all delays, taking longer and swimming farther to find the platform on the second swims than did sham-operated controls. By contrast, rats with PRh lesions displayed normal DMTP acquisition and performance. The results suggest that, unlike the functions of HPC, those of PRh are not critical for allocentric spatial working memory.

Prenatal ethanol exposure can produce cognitive and behavioral impairments. In the present study, rats from prenatal ethanol (E), pair-fed (PF), and ad libitum-fed control (C) treatment conditions were tested on the object-recognition delayed-nonmatching-to-sample (DNMS) task with nonrecurring items and on the spatial-navigation Morris water maze task. In Experiment 1, there were no significant differences among groups in object-recognition learning and memory, distractibility, or response perseveration on the DNMS task. In Experiment 2, the same rats were tested in the water maze; E rats took significantly longer to learn the task than did the PF or C rats. These data suggest that the mechanisms underlying spatial cognitive abilities are more vulnerable to the teratogenic effects of prenatal ethanol exposure than those underlying object-recognition abilities.

The literature on the role of the hippocampus in object-recognition contains a paradox: Transient forebrain ischemia (ISC) produces hippocampal damage and severe deficits on the delayed nonmatching-to-sample (DNMS) task, yet hippocampal ablation (ABL) produces milder deficits. Experiment 1 confirmed that pretrained rats display severe DNMS deficits following ISC, but not ABL. Ischemia produced loss of CA1 neurons, but no obvious extrahippocampal damage. In Experiments 2 and 3, ISC rats from Experiment 1 received ABL, and ABL rats received ISC; neither treatment affected DNMS performance. In Experiment 4, rats that received ISC followed 1 hr later by ABL displayed only mild deficits. It is hypothesized that ISC-induced DNMS deficits are due to extrahippocampal damage produced by pathogenic processes that involve the hippocampus.

Pyrithiamine-induced thiamine deficiency (PTD) in rats is used to model the etiology, diencephalic neuropathology, and memory deficits of Korsakoff's amnesia. We assessed the performance of rats exposed to PTD on a test of object recognition--nonrecurring-items delayed nonmatching-to-sample (DNMS). PTD produced thalamic lesions similar to those of Korsakoff's amnesics and similar to those previously observed in PTD rats. PTD rats required more trials to master DNMS at a 4-s retention delay than did controls, and after they had done so, they performed more poorly than controls at delays of 15, 30, 60, and 120 s. DNMS deficits were also observed in PTD rats that received training prior to PTD treatment. These findings support the validity of the PTD rat model of Korsakoff's disease by demonstrating that PTD rats display object-recognition deficits that are similar to those reported in Korsakoff amnesics.

Although rats (Rattus norvegicus) spend much of their lives in the darkness of burrows, defensive behavior in the dark has rarely been studied. We compared rats' reactions to aversive stimuli in dark and lighted 2-alley, burrowlike environments. Experiment 1 assessed reactions to an unsignaled airblast; Experiment 2 assessed neophobic reactions to an unfamiliar steel ball. Half of the rats were tested in light and half, in total darkness. In both experiments rats directed defensive burying and stretched approach toward the aversive stimulus. Darkness increased airblast-induced burying behavior but not burying behavior toward the unfamiliar object; it had no effect on stretched-approach behavior in either experiment. Because the location and nature of the aversive stimulus was ambiguous in Experiment 1 but not in Experiment 2, these results support the hypothesis that risk assessment is one function of defensive-burying behavior.

Rats with bilateral lesions of lateral entorhinal cortex and perirhinal cortex were tested on a nonrecurring-items delayed nonmatching-to-sample (DNMS) task resembling the one that is commonly used to study object recognition in monkeys. The rats were tested at retention delays of 4 s, 15 s, 60 s, 120 s, and 600 s before and after surgery. After surgery, they displayed a delay-dependent deficit: They performed normally at the 4-s delay but were impaired at delays of 15 s or longer. The addition of bilateral amygdala lesions did not increase their DNMS deficits. The present finding of a severe DNMS deficit following rhinal cortex damage is consistent with the authors' previous finding that bilateral lesions of the hippocampus and amygdala cause only mild DNMS deficits in rats unless there is also damage to rhinal cortex (D.G. Mumby, E.R. Wood, & J.P.J. Pinel, 1992). These findings add to accumulating evidence that the rhinal cortex, but not the amygdala, plays a critical role in object recognition.

Transient cerebral ischemia can produce irreversible neuronal damage and permanent learning and memory impairments in humans. This study examined whether ischemia-induced brain damage in rats results in impairments on the delayed nonmatching-to-sample (DNMS) task, a nonspatial recognition task analogous to tests on which amnesic patients display impairments. Male Wistar rats received either sham surgery or 20-min forebrain ischemia induced by bilateral carotid occlusion and hypotension. Four weeks after surgery, ischemic rats were significantly impaired in both learning and performing the DNMS task at retention intervals up to 5 min. Extensive presurgical training did not reduce this impairment. Observable cell loss in ischemic rats was limited to CA1 pyramidal neurons and a subset of cells in the dentate gyrus. The results indicate that ischemic damage to the hippocampus in rats results in recognition memory deficits similar to those produced by ischemic damage in humans.

Rats behaviorally anticipate a fixed, daily opportunity to feed by entrainment of circadian oscillators that are physically separate from the light-entrainable circadian pacemaker that has been localized to the suprachiasmatic nucleus. Neural substrates mediating food-entrained rhythms are unknown. A variety of anatomical and functional observations suggest possible involvement of the limbic system and its dopaminergic component in the regulation of these rhythms. To test this hypothesis, the activity rhythms of rats bearing large, combined ablations of the hippocampus and amygdala or nucleus accumbens and medical forebrain anterior to the thalamus were examined under ad-lib feeding, 2 h daily feeding, and total food deprivation conditions. Some hippocampal-ablated rats showed alterations of free-running rhythms under ad-lib feeding, but none of the ablations impaired the rats' ability to anticipate daily feeding, or 'remember' the phase of feeding time during subsequent food deprivation. Additional groups of intact rats were treated with the dopamine antagonist haloperidol (0.3 mg/kg or 2.0 mg/kg) 30 min prior to daily feeding, but this also did not prevent the emergence of food-entrained rhythms. The limbic and dopamine systems do not appear to play a necessary role in the generation or entrainment of food-anticipatory circadian rhythms.

This study examined a program attaching public health nurses to specific family physicians practicing in the community. It compared the work of attached and nonattached public health nurses in both the urban and rural sections of a health district in Ontario, Canada. It found that attached nurses receive a greater proportion of their referrals from family physicians, see a greater percentage of elderly patients, and deal with proportionately more psychosocial cases. The study also indicated that the attached public health nurse does not complain of physician misuse of her services and that, once a referral has been made, communication between the physician and public health nurse improves.

The effect of food texture on the development of schedule-induced polydipsia was examined in six groups of rats (n = 8), each receiving one of six grades of food granulation. A seventh group received pellets. By the end of 15 sessions of FT 60-sec food delivery, rats receiving pellets and the coarser granulations had developed polydipsia. The volume of water drunk at asymptote by the remaining groups declined with decreased coarseness of the food. Ethological analyses of the behavioral repertoire of the rats during the fifteenth session showed that the polydipsic groups sustained their drinking throughout the session, rather than turning from ingestive to exploratory behaviors near the end of the session, as was the case with animals receiving finer granulations. The enhanced drinking induced by the coarser food texture was reciprocally related to the amount of time the animal spent with its head in the feeder hole during the period of maximum drinking. The results support the conclusion that the schedule-induced polydipsia traditionally demonstrated with pellets as the reinforcer is critically dependent on the fact that pellets are coarse in texture.