Rats with fimbria-fornix lesions can acquire and retain a visual-tactile transwitching (configural) task.

The idea that the hippocampus is essential for acquisition and retention of a transwitching (configural) problem is evaluated with a visual-tactile task. The task requires the rats to pull up a string of one of two sizes for food, as signalled by room lighting conditions. Rats received cathodal fimbria-fornix lesions either prior to or after learning the task. Rats with fimbria-fornix lesions were unimpaired in acquisition or retention. The results do not support the position that the hippocampal formation is essential for the acquisition and retention of a transwitching configural problem. The result is discussed in relation to the configural theory of hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Dissociation of the effects of bilateral lesions of the dorsal hippocampus and parietal cortex on path integration in the rat.

Rodents are able to rely on self-motion (idiothetic) cues and navigate toward a reference place by path integration. The authors tested the effects of dorsal hippocampal and parietal lesions in a homing task to dissociate the respective roles of the hippocampus and the parietal cortex in path integration. Hippocampal rats exhibited a strong deficit in learning the basic task. Parietal rats displayed a performance impairment as a function of the complexity of their outward paths when the food was placed at varying locations. These results suggest that the parietal cortex plays a specific role in path integration and in the processing of idiothetic information, whereas the hippocampus is involved in the calibration of space used by the path integration system. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Angular velocity and head direction signals recorded from the dorsal tegmental nucleus of gudden in the rat: Implications for path integration in the head direction cell circuit.

When a rat navigates through space, head direction (HD) cells provide an ongoing signal of the rat's directional heading. It is thought that these cells rely, in part, on angular path integration of the rat's head movements. This integration requires that the HD cell system receive information about angular head movements and that this information be combined with the current directional signal, to generate the next "predicted" direction. Recent data suggest that the dorsal tegmental nucleus (DTN) may play a critical role in helping to generate the HD cell signal. To test this, recordings were made from cells in the DTN in freely moving rats. The following cell types were found: (a) "classic" HD cells, (b) angular velocity cells, and (c) cells that fired as a function of both head direction and angular velocity. Thus, DTN cells exhibit firing characteristics that are critical to the neural circuit hypothesized for generation of the HD cell signal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Increased 5-HT1A receptor immunoreactivity in the rat hippocampus following 5,7-dihydroxytryptamine lesions in the cingulum bundle and fimbria-fornix

Serotonin (5-HT) projections from the ascending raphe nuclei reach the dorsal hippocampus via the cingulum bundle (CB) and fimbria-fornix (FF). Microinjection of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into the CB and FF produces a significant decrease in the density of 5-HT immunoreactive fibers in the hippocampus as early as 3 days postlesion (Zhou, F.C. and Azmitia, E.C. (1983) Brain Res. Bull., 373, 337-348). In the present study we used an anti-peptide antibody against the second extracellular loop of the 5-HT1A receptor and employed immunocytochemistry to examine changes in the expression and distribution of the 5-HT1A receptor in the hippocampus 14 days following administration of 5,7-DHT into the CB and FF. The density of 5-HT immunoreactive fibers was greatly reduced 14 days following the lesions. 5-HT1A immunoreactivity (IR) was localized to the proximal axon near the axon hillock of cells in the pyramidal cell layer of the cornu Ammonus and in the granule cell layer of the dentate gyrus. The intensity of 5-HT1A-IR was increased in the CA1 and dentate gyrus following 5,7-DHT lesions. Intensity in the CA3 also increased but not to a significant level. These findings demonstrate that 5-HT denervation in the hippocampus is followed by increased expression of the 5-HT1A receptor protein. These changes in receptor expression 14 days postlesion may represent adaptive changes by postsynaptic cells following reduced 5-HT innervation and may be the molecular basis for 5-HT1A receptor supersensitivity.     

Deficits in landmark navigation and path integration after lesions of the interpeduncular nucleus.

Experiments were designed to determine the role of the interpeduncular nucleus (IPN) in 3 forms of navigation: beacon, landmark, and path integration. In beacon navigation, animals reach goals using cues directly associated with them, whereas in landmark navigation animals use external cues to determine a direction and distance to goals. Path integration refers to the use of self-movement cues to obtain a trajectory to a goal. IPN-lesioned rats were tested in a food-carrying task in which they searched for food in an open field, and returned to a refuge after finding the food. Landmark navigation was evaluated during trials performed under lighted conditions and path integration was tested under darkened conditions, thus eliminating external cues. We report that IPN lesions increased the number of errors and reduced heading accuracy under both lighted and darkened conditions. Tests using a Morris water maze procedure indicated that IPN lesions produced moderate impairments in the landmark version of the water task, but left beacon navigation intact. These findings suggest that the IPN plays a fundamental role in landmark navigation and path integration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence for the use of an internal sense of direction in homing.

Path integration, the ability to maintain a representation of location and direction on the basis of internal cues, is thought to be important for navigation and the learning of spatial relationships. Representations of location and direction in the brain, such as head direction cells, grid cells, and place cells in the limbic system, are thought to underlie navigation by path integration. While this idea is generally consistent with lesion studies, the relationship between such neural activity and behavior has not been studied on a task where animals demonstrably use a path integration strategy. Here we report the development of such a task in rats: by slowly rotating rats before their return to a trial-unique home base, we could show subjects relied on internal cues only to navigate. To illustrate how this task can be combined with recording, we show examples of simultaneously recorded head direction cells in which neural activity is closely related to rats’ homing direction. These results support the notion that rats can navigate by path integration, that this ability depends on head direction cells, and suggest a convenient behavioral paradigm for investigating the neural basis of navigation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preserved negative patterning and impaired spatial learning in pigeons (Columba livia) with lesions of the hippocampus.

Pigeons (Columba livia) with bilateral electrolytic lesions of the hippocampus and area parahippocampalis were compared with control pigeons on 2 tasks: negative patterning and delayed spatial alternation. Negative patterning demands configural stimulus representations for its successful solution. The only effect of hippocampal lesions on this task was an increased response rift to the rewarded stimuli. On the delayed spatial alternation task, hippocampal birds showed deficits relative to controls. Differences in the results of prior studies on negative patterning appear to be due to different response requirements to the nonreinforced stimuli. These results are consistent with prior work with rats and suggest that the avian hippocampus is essential for spatial memory and response inhibition but is not involved in configural learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Rats with damage to the hippocampal-formation are impaired on the transverse-patterning problem but not on elemental discriminations.

We assessed the effects of hippocampal-formation (HF) damage on the rat's ability to learn two sets of concurrent visual discriminations. Each set included three problems. One set, called the transverse-patterning problem, was constructed so that each choice stimulus was ambiguous; sometimes it was the correct (+) and sometimes it was the incorrect (–) choice as follows: A+ vs B–, B+ vs C–, and C+ vs A–. It could not be solved unless rats used configural associations. The stimuli were not ambiguous in the second, elemental problem set, A+ vs B–, C+ vs D–, and E+ vs F–. Rats could solve this set without the use of configural associations. Rats with HF damage solved the set of elemental problems, but their performance on the transverse-patterning problem was impaired. These results support Sutherland and Rudy's (see record 1989-38933-001) theory that the hippocampal formation is critical for the acquisition of configural associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral effects of GM1 ganglioside treatment and intrahippocampal septal grafts in rats with fimbria-fornix lesions

The monosialoganglioside GM1 is a compound with neurotrophic properties found to foster functional recovery in various paradigms of brain damage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix lesions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated. Fourteen days later, half the lesioned rats were subjected to intrahippocampal grafts of a fetal septal cell suspension. Starting a few hours after lesion surgery and over a 2-month period, half the rats of each surgical treatment group received a daily injection of GM1 (30 mg/kg i.p.), the other half being injected with saline as a control. All rats were subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning performances in both an uninterrupted and an interrupted radial maze testing procedure. In all rats with surviving grafts, the grafts had provided the hippocampus with a new and dense organotypic acetylcholinesterase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ significantly from those of their respective lesion-only counterparts. However, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated counterparts: they used more efficient visit patterns under the uninterrupted testing conditions and made fewer errors under the interrupted ones. The results suggest that GM1 treatment or intrahippocampal grafts used separately do not attenuate the lesion-induced behavioral deficits measured in this experiment. However, when GM1 treatment and grafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.     

Illness-induced context aversion learning in rats with lesions of the dorsal hippocampus

In 2 experiments, rats with electrolytic lesions of the dorsal hippocampus and sham-operated control subjects were given injections of lithium chloride after exposure to a distinctive context. This procedure establishes a context-illness association in intact subjects. In Experiment 1, the strength of the context aversion was assessed by measuring the subjects' willingness to consume a novel flavor in the context. It was found that lesioned subjects showed less suppression of consumption than controls. Experiment 2 tested the ability of the context to block subsequent flavor-aversion learning and revealed less effective blocking in lesioned rats. These results are consistent with the view that hippocampal lesions retard context conditioning; unlike previous work that has made use of conditioned freezing as the measure of context conditioning, the present results are not explicable in terms of lesion-induced changes in general activity.     

The avian hippocampus: Evidence for a role in the development of the homing pigeon navigational map.

Young homing pigeons were subjected to hippocampal lesion before being placed in their permanent loft to examine what effect such treatment may have on the development of their navigational map, which supports homing from distant unfamiliar locations. When later released from 3 distant unfamiliar locations, the hippocampal-lesioned pigeons were impaired in taking up a homeward bearing. The results identify a deficit in the acquisition of navigational ability after hippocampal ablation in homing pigeons. The results suggest a deficit in navigational map acquisition, but alternative interpretations cannot be excluded. The findings offer the first insight into the central neural structures involved in the acquisition of the pigeon navigational map. Further, the results identify the hippocampus as a structure critical for the regulation of navigational behavior that manifests itself in a natural setting. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Enhancement of latent inhibition in rats with electrolytic lesions of the hippocampus.

Two groups of rats—1 with electrolytic lesions of the hippocampus and 1 consisting of sham-operated controls—received flavor-aversion conditioning with 2 flavors. All subjects had received prior nonreinforced exposure to Flavor A. Latent inhibition was apparent in slower acquisition of the aversion to Flavor A than to Flavor B. Hippocampal lesions had no effect on acquisition to the nonpreexposed Flavor B but produced a marked enhancement of the latent inhibition effect. The contrast between this result and previous findings of an attenuation of latent inhibition in subjects with hippocampal lesions is discussed (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial prefrontal lesions in the rat and spatial navigation: Evidence for impaired planning.

Rats with medial prefrontal cortical lesions were tested in a modified water maze navigation task. In Stage 1, the rats were trained to locate a hidden platform from a single start location. They were then subjected to a series of trials during which a second start position was used (Stage 2). In Stage 3, the rats had to navigate to a new goal location from the 2 experienced start positions. Stage 4 required the rats to navigate to the same goal as in Stage 3, starting from 4 distinct positions. Finally, a single probe trial with no platform was conducted. Rats with prefrontal lesions were impaired only during Stage 4. This deficit was specific to the 2 start positions newly introduced during this stage, suggesting a dysfunction of planning processes. This impairment might result from a working memory deficit, precluding the animal from forming an adequate representation of the whole course of movements required to reach the platform. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Path integration and lesions within the head direction cell circuit: Comparison between the roles of the anterodorsal thalamus and dorsal tegmental nucleus.

Experiments were designed to determine whether 2 regions of the head direction cell circuit, the anterodorsal thalamic nucleus (ADN) and the dorsal tegmental nucleus (DTN), contribute to navigation. Rats were trained to perform a food-carrying task with and without blindfolds prior to receiving sham lesions or bilateral lesions of the ADN or DTN. ADN-lesioned rats were mildly impaired in both versions of the task. DTN-lesioned rats, however, were severely impaired and showed reduced heading accuracy in both task versions. These findings suggest that although both the DTN and ADN contribute to navigation based on path integration and landmarks, disruption of the head direction cell circuit at the level of the DTN has a significantly greater effect on spatial behavior than lesions of the ADN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Context- but not familiarity-dependent forms of object recognition are impaired following excitotoxic hippocampal lesions in rats.

Dual-process models of recognition memory in animals propose that recognition memory is supported by two independent processes that reflect the operation of distinct brain structures: a familiarity process that operates independently of the hippocampus and a context-dependent (episodic) memory process that is dependent on the hippocampus. A novel variant of an object recognition procedure was used to examine this proposal. Healthy rats showed a preference for exploring a novel object rather than a familiar object: a familiarity-dependent recognition effect. They also showed a preference for exploring a familiar object that was presented in a different spatiotemporal context rather than a familiar object that was presented either in a different spatial or temporal context: a context-dependent form of recognition that is sensitive to "what" object has been presented "where" and "when." Rats with excitotoxic hippocampal lesions showed the familiarity-dependent but not the context-dependent form of recognition. The results provide support for dual-process theories of recognition memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Memory for duration: role of hippocampus and medial prefrontal cortex

In this task rats had to learn that a three-dimensional object stimulus (a rectangle) that was visible for 2 s would result in a positive (go) reinforcement for one object (a ball) and no reinforcement (no go) for a different object (a bottle). However, if the rectangle stimulus was visible for 8 s then there would be no reinforcement for the ball (no go), but a reinforcement for the bottle (go). After rats learned this conditional discrimination by responding differentially in terms of latency to approach the object, they received large (dorsal and ventral) lesions of the hippocampus, lesions of the medial prefrontal cortex (anterior cingulate and precentral cortex), lesions of the cortex dorsal to the dorsal hippocampus, or served as sham-operated controls. Following recovery from surgery they were retested. The results indicate that there were major impairments following hippocampal lesions, in contrast to cortical control and medial prefrontal cortex lesions, as indicated by smaller latency differences between positive and negative trials on postsurgery tests. In order to ensure that the deficits observed with hippocampal lesions were not due to a discrimination problem, new rats were trained in an object (gray cylinder) duration discrimination task. In this go/no go procedure, the rats were reinforced for a 2-s exposure (duration) of the gray cylinder, but not a 10-s duration, or vice versa. The results indicate that after hippocampal lesions, there was an initial deficit followed by complete recovery. There were no significant changes for the medial prefrontal, cortical control, or sham-operated animals. It appears that the hippocampus, but not the medial prefrontal cortex, is actively involved in representing in short-term memory temporal attribute information based on the use of markers for the beginning and end of the presence (duration) of a stimulus (object).     

Retrograde amnesia for spatial information: a dissociation between intra and extramaze cues following hippocampus lesions in rats

Several recent studies have shown a flat retrograde amnesia for spatial information following lesions to the hippocampus in rats and mice. However, the results of the present investigation demonstrate that in rats that presurgically learned a spatial reference memory task based on extramaze cues, a temporally graded retrograde amnesia is evident following lesions to the hippocampus (1, 16, 32 or 64 days after learning) if two conditions are met. First, that a wide range of retention intervals is used, and second, that independent groups of rats are tested, not a single group that learns different spatial discrimination tasks at different times (expt 1). The results of expt 2 show that the hippocampus does not serve as a consolidating mechanism when the spatial task learned presurgically is based on intramaze cues. Taken together, these results indicate that the hippocampus is critical for the storage and/or retrieval of spatial reference information that was learned up to 1 month before hippocampus damage; however, in the absence of the hippocampus, efficient retention can still occur provided that the spatial knowledge was learned in a simple associative manner.     

Care in psychiatry--caring for and supervising is possible with a "parent role"

The effect of superoxide dismutase (SOD) and selenium on the blood level of ferritin and transferrin in patients with hemoblastosis was studied. Two-month treatment with SOD and selenium had no effect on the level of ferritin but reduced the concentration of malonic dialdehyde (MDA) in the native erythrocytes in patients with chronic lymphoid leukemia practically to that in healthy individuals. In erythrocytes which formed from cells of the leukemic clone (chronic myelocytic leukemia and erythremia) treatment with SOD and selenium reduced the pathologically high level of ferritin, but at the same time increased the concentration of MDA in the erythrocytes. In erythremia in the group with a low level of ferritin SOD and selenium caused no statistically significant increase in its level in blood.     

Alzheimer amyloid protein precursor in the rat hippocampus: transport and processing through the perforant path

Amyloid deposition is a neuropathological hallmark of Alzheimer's disease. The principal component of amyloid deposits is beta amyloid peptide (Abeta), a peptide derived by proteolytic processing of the amyloid precursor protein (APP). APP is axonally transported by the fast anterograde component. Several studies have indicated that Abeta deposits occur in proximity to neuritic and synaptic profiles. Taken together, these latter observations have suggested that APP, axonally transported to nerve terminals, may be processed to Abeta at those sites. To examine the fate of APP in the CNS, we injected [35S]methionine into the rat entorhinal cortex and examined the trafficking and processing of de novo synthesized APP in the perforant pathway and at presynaptic sites in the hippocampal formation. We report that both full-length and processed APP accumulate at presynaptic terminals of entorhinal neurons. Finally, we demonstrate that at these synaptic sites, C-terminal fragments of APP containing the entire Abeta domain accumulate, suggesting that these species may represent the penultimate precursors of synaptic Abeta.     

The role of the hippocampus in memory for the temporal order of a sequence of odors.

Memory for the temporal order of a sequence of odors was assessed in rats. A sequence of 5 odors mixed in sand was presented in digging cups, 1 at a time, to each rat in a sequence that varied on each trial. A reward was buried in each cup. After the 5th odor, 2 of the previous 5 odors were presented simultaneously; to receive a reward, the rat had to choose the odor that occurred earliest in the sequence. Temporal separations of 1, 2, or 3 represented the number of odors that occurred between the 2 odors in the sequence. Once a preoperative criterion was reached, each rat received a hippocampal (HIP) or cortical control lesion and was retested on the task. On postoperative trials, the HIP group was impaired relative to controls. However, the HEP group could discriminate between the odors. The data suggest that the hippocampus is involved in separating sensory events in time so that 1 event can be remembered separately from another event. (PsycINFO Database Record (c) 2010 APA, all rights reserved)