Biomedical subjects

D M Bannerman

Publications and source records attributed to D M Bannerman.

At least 19 recordsLinked to original sources

PubMed2003

Ventral hippocampal lesions affect anxiety but not spatial learning.

Rats with cytotoxic ventral hippocampal lesions which removed approximately 50% of the hippocampus (including dentate gyrus) starting from the temporal pole, displayed a reduction in freezing behaviour following the delivery of an unsignalled footshock in an operant chamber. This was more plausibly a result of reduced susceptibility to fear than a result of a lesion-induced increase in general motor activity. There was no consistent difference between sham and lesioned animals in spontaneous locomotor activity, or locomotion following acute or chronic treatment with amphetamine. In contrast, ventral hippocampal lesioned animals were quicker to pass from the black to the white box during a modified version of the light/dark exploration test, and were quicker to begin eating during tests of hyponeophagia. Furthermore, rats with ventral hippocampal lesions defecated less than their sham counterparts both during open field testing and in extinction sessions following contextual conditioning. In contrast to these clear lesion effects, there were no signs of any spatial learning impairment either in the watermaze or on the elevated T-maze. Taken together these results suggest that the ventral hippocampus may play a role in a brain system (or systems) associated with fear and/or anxiety, and provide further evidence for a distinct specialisation of function along the septotemporal axis of the hippocampus.

Amphetamine↗

PubMed2003

Learning associations between places and visual cues without learning to navigate: neither fornix nor entorhinal cortex is required.

Rats with fornix transection, or with cytotoxic retrohippocampal lesions that removed entorhinal cortex plus ventral subiculum, performed a task that permits incidental learning about either allocentric (Allo) or egocentric (Ego) spatial cues without the need to navigate by them. Rats learned eight visual discriminations among computer-displayed scenes in a Y-maze, using the constant-negative paradigm. Every discrimination problem included two familiar scenes (constants) and many less familiar scenes (variables). On each trial, the rats chose between a constant and a variable scene, with the choice of the variable rewarded. In six problems, the two constant scenes had correlated spatial properties, either Allo (each constant appeared always in the same maze arm) or Ego (each constant always appeared in a fixed direction from the start arm) or both (Allo + Ego). In two No-Cue (NC) problems, the two constants appeared in randomly determined arms and directions. Intact rats learn problems with an added Allo or Ego cue faster than NC problems; this facilitation provides indirect evidence that they learn the associations between scenes and spatial cues, even though that is not required for problem solution. Fornix and retrohippocampal-lesioned groups learned NC problems at a similar rate to sham-operated controls and showed as much facilitation of learning by added spatial cues as did the controls; therefore, both lesion groups must have encoded the spatial cues and have incidentally learned their associations with particular constant scenes. Similar facilitation was seen in subgroups that had short or long prior experience with the apparatus and task. Therefore, neither major hippocampal input-output system is crucial for learning about allocentric or egocentric cues in this paradigm, which does not require rats to control their choices or navigation directly by spatial cues.

Animals↗

PubMed2003

Entorhinal cortex lesions disrupt the transition between the use of intra- and extramaze cues for navigation in the water maze.

This study with rats examined the effects of excitotoxic lesions to the entorhinal cortex (EC) and hippocampus (HPC) on using extramaze and intramaze cues to navigate to a hidden platform in a water maze. HPC lesions resulted in a disruption to the use of extramaze cues, but not intramaze cues, whereas EC lesions had no effect on the use of these cues when they were encountered for the first time. However, prior navigation training in which 1 type of cue was relevant disrupted navigation with the other type in rats with EC lesions. Results show that the EC contributes to the processing of spatial information, but that this contribution is most apparent when there is a conflict between 2 sources of navigational cues in the water maze.

Animals↗

PubMed2003

GluR-A-Deficient mice display normal acquisition of a hippocampus-dependent spatial reference memory task but are impaired during spatial reversal.

Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-A(-/-) mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampalgroup remained at chance levels. In contrast to their performance during acquisition, the GluR-A(-/-) mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term, flexible spatial working memory impairment in GluR-A(-/-) mice, which might also underlie their mild deficit during spatial reversal.

Animals↗

PubMed2002

Double dissociation of function within the hippocampus: spatial memory and hyponeophagia.

Complete and dorsal hippocampal lesions impaired spatial performance on 2 working memory tasks: rewarded alternation on the T maze and matching to position in the water maze. In contrast, ventral hippocampal lesions had no effect on these tasks, even when task difficulty was increased by the introduction of delays. Ventral lesions did resemble complete lesions in reducing anxiety in 3 commonly used tests of anxiety (social interaction, plus-maze, and hyponeophagia). Dorsal lesions also appeared to be anxiolytic in the social interaction and plus-maze tests, but they did not affect hyponeophagia. Complete- and dorsal-lesioned rats displayed hyperactivity, whereas ventral-lesioned rats did not. These results show a double dissociation between dorsal and ventral hippocampal lesions (hyponeophagia vs. spatial memory), suggesting differentiation of function along the septotemporal axis of this structure.

Amphetamine↗

PubMed2002

Spatial memory dissociations in mice lacking GluR1.

Gene-targeted mice lacking the AMPA receptor subunit GluR1 (GluR-A) have deficits in hippocampal CA3-CA1 long-term potentiation. We now report that they showed normal spatial reference learning and memory, both on the hidden platform watermaze task and on an appetitively motivated Y-maze task. In contrast, they showed a specific spatial working memory impairment during tests of non-matching to place on both the Y-maze and an elevated T-maze. In addition, successful watermaze and Y-maze reference memory performance depended on hippocampal function in both wild-type and mutant mice; bilateral hippocampal lesions profoundly impaired performance on both tasks, to a similar extent in both groups. These results suggest that different forms of hippocampus-dependent spatial memory involve different aspects of neural processing within the hippocampus.

Animals↗

PubMed2001

Selective cytotoxic lesions of the retrohippocampal region produce a mild deficit in social recognition memory.

Although a number of studies have implicated the hippocampal formation in social recognition memory in the rat, a recent study in this laboratory has demonstrated that selective cytotoxic lesions, confined to the hippocampus proper (encompassing the four CA subfields and the dentate gyrus), are without effect on this behaviour. This finding suggests that the hippocampus proper does not subserve social recognition memory in the rat, but does not preclude the possibility that other areas of the hippocampal formation, such as the entorhinal cortex or subiculum, could support this form of learning. The present study addressed this issue by examining the effects of selective cytotoxic retrohippocampal (RHR) lesions (including both the entorhinal cortex and subiculum) on social recognition memory in the rat. RHR lesions produced a mild social recognition memory impairment, although lesioned animals still displayed a reduction in investigation time between the first and second exposure to the juvenile. This result is consistent with other studies which have implicated the retrohippocampal or parahippocampal area in olfactory recognition memory processes. It also suggests, however, that other areas, out with the retrohippocampal region, are also likely to play an important role in social recognition memory.

Age Factors↗

PubMed2001

Faster is not surer--a comparison of C57BL/6J and 129S2/Sv mouse strains in the watermaze.

In recent years the use of genetic manipulations to investigate the molecular mechanisms underlying learning and memory has become a common approach. In a great many cases, the spatial learning ability of mutant mice has been assessed using the Morris watermaze task. The performance of these mice may, however, be strongly influenced by their genetic background and, therefore, the interpretation of their phenotype requires a preliminary characterization of the parental strains. The present study compared 129S2/Sv and C57/BL/6J inbred mouse strains, which have been widely used in deriving lines of genetically modified mice, on the hidden platform version of the watermaze task. During acquisition, the C57 mice displayed shorter escape latencies to find the platform than the 129S2s. Further analysis revealed, however, that the C57 mice also swam faster than the 129S2s. The analysis of path lengths was thus a more reliable measure of spatial learning, and revealed an equal level of performance in the two strains. This conclusion was confirmed during the two probe trials with both strains showing a similar spatial preference for the training site. These results suggest that the 129S2 substrain is no less proficient than the C57 substrain in terms of spatial learning in the watermaze, and also demonstrates the importance of not relying solely on escape latency as a measure of watermaze performance.

Animals↗

PubMed2001

Cytotoxic lesions of the hippocampus increase social investigation but do not impair social-recognition memory.

A number of studies have implicated the hippocampal formation in social-recognition memory in the rat. The present study addressed this issue directly by assessing the effects of cytotoxic lesions confined to the hippocampus proper, encompassing the four CA subfields and the dentate gyrus, on this behavioural task. Ibotenate-induced hippocampal lesions led to locomotor hyperactivity and a marked spatial working-memory impairment on the elevated T-maze. In addition, they also led to increased social investigation. However, despite these clear effects, there was no effect of the lesions on social-recognition memory. These results suggest that the hippocampus proper does not subserve social-recognition memory; but does not, however, preclude the possibility that other areas of the hippocampal formation (e.g. entorhinal cortex or subiculum) may support this memory process.

Animals↗

PubMed2001

The time course of the hyperactivity that follows lesions or temporary inactivation of the fimbria-fornix.

Lesions of the hippocampus or the fimbria-fornix produce a pronounced hyperactivity in rats. This effect is thought to be due to the loss of glutamatergic hippocampal inputs to the nucleus accumbens, although the mechanisms involved remain unclear. It has been suggested that the hyperactivity is due to changes in accumbens dopamine receptors, possibly involving the gradual development of denervation supersensitivity. Consistent with this possibility, the present study found that fimbria-fornix transection produced hyperactivity which, although undetectable immediately after surgery, gradually became apparent and then continued to increase over the course of several days. This does not, however, preclude the possibility that there is an immediate increase in activity which is masked by the after effects of surgery. To address this issue, local anaesthetic was infused into the fimbria-fornix via chronic indwelling cannulae, in order to silence the hippocampal inputs to the nucleus accumbens. This procedure impaired spatial working memory on the elevated T-maze and resulted in immediate hyperactivity, suggesting that there may be at least two components to fornix lesion-induced hyperactivity, and that the immediate effects of mechanical fornix lesions on activity levels may be masked by the after effects of surgery per se.

Anesthetics, Local↗

PubMed2001

The role of the entorhinal cortex in two forms of spatial learning and memory.

It is generally acknowledged that the rodent hippocampus plays an important role in spatial learning and memory. The importance of the entorhinal cortex (ERC), an area that is closely interconnected anatomically with the hippocampus, in these forms of learning is less clear cut. Recent studies using selective, fibre-sparing cytotoxic lesions have generated conflicting results, with some studies showing that spatial learning can proceed normally without the ERC, suggesting that this area is not required for normal hippocampal function. The present study compared cytotoxic and aspiration ERC lesions with both fimbria fornix (FFX) lesions and sham-operated controls on two spatial learning tasks which have repeatedly been shown to depend on the hippocampus. Both groups of ERC lesions were impaired during non-matching-to-place testing (rewarded alternation) on the elevated T-maze. However, neither of these lesions subsequently had any effect on the acquisition of a standard spatial reference memory task in the water maze. FFX lesions produced a robust and reliable impairment on both of these tasks. A second experiment confirmed that cytotoxic ERC lesions spared water maze learning but disrupted rewarded alternation on the T-maze, when the order of behavioural testing was reversed. These results confirm previous reports that ERC-lesioned animals are capable of spatial navigation in the water maze, suggesting that the ERC is not a prerequisite for normal hippocampal function in this task. The present demonstration that ERC lesions disrupt non-matching-to-place performance may, however, be consistent with the possibility that ERC lesions affect attentional mechanisms, for example, by increasing the sensitivity to recent reward history.

Animals↗

PubMed2001

Contextual fear conditioning is disrupted by lesions of the subcortical, but not entorhinal, connections to the hippocampus.

Recent studies have questioned the importance of the entorhinal cortex (ERC) for normal hippocampal function. For example, fibre-sparing ERC lesions have been found to have no effect on spatial learning in the watermaze. There is also doubt as to the importance of the ERC for contextual fear conditioning, with previous studies having yielded conflicting results. In an attempt to resolve this issue, the present study compared aspiration and cytotoxic ERC lesioned rats, along with fimbria-fornix (FFX) lesioned animals and sham operated controls, on an unsignalled contextual fear conditioning paradigm. The results of the present study show that whereas lesions of the FFX disrupted contextual freezing, neither aspiration nor cytotoxic ERC lesions had any effect on this behaviour. Aspiration ERC lesioned rats, however, like FFX lesioned animals, did display hyperactivity prior to the delivery of footshock. These results suggest that whereas projections between the hippocampus and subcortical structures are important for normal levels of contextual freezing, projections from the entorhinal cortex are not essential.

Animals↗

PubMed2001

Rats' processing of visual scenes: effects of lesions to fornix, anterior thalamus, mamillary nuclei or the retrohippocampal region.

We analysed the effects of lesions of hippocampal-diencephalic projections -- fornix (FX) mamillary bodies (MB) and anterior thalamic nuclei (AT) -- and retrohippocampal (RH) lesions including entorhinal cortex and ventral subiculum, upon scene processing. All lesions except FX were neurotoxic. Rats learned to discriminate among computer-generated visual displays ("scenes") each comprising three different shapes ("objects"). The paradigm was constant-negative; one constant scene (unrewarded) appeared on every trial together with a trial-unique variable scene (rewarded). Four types of variable scene were intermingled: (1) unfamiliar objects in different positions from those of the constant (type O+P), (2) unfamiliar objects in same positions as in the constant (type O), (3) same objects as the constant in different positions (type P), (4) same objects and positions as the constant but recombined (type X). Group RH performed like controls while groups FX, AT and MB showed (surprisingly) enhanced performance on types X and O. One explanation is that normal rats attempt to process all objects in a scene concurrently, while hippocampal-projection lesions disrupt this tendency, producing a narrower attention, which paradoxically aids performance with some variable types. The results confirm that the entorhinal cortex has a different function from other components of the hippocampal system.

Animals↗

PubMed2001

The effect of cytotoxic lesions of the hippocampus on recognition memory in the rat: effects of stimulus size.

Rats with excitotoxic hippocampal lesions were trained on delayed nonmatching-to-sample (DNMS) with small goal boxes, containing complex objects, presented on a pseudo trial-unique schedule. A series of experiments then tested performance on repeated presentation of either the small object or large empty goal boxes. All rats acquired the nonmatching rule, but hippocampal-lesioned rats performed less well than controls on choice accuracy for the final 2 blocks of acquisition. In the study's main phase, the lesions impaired choice accuracy when the large empty boxes were used as stimuli. This deficit was ameliorated when the rats were tested with the small object boxes, although the performance of the hippocampal-lesioned rats was still below that of controls. These results extend previous reports of box size-dependent effects of hippocampal aspiration lesions on DNMS and suggest that selective damage to the hippocampus, not neuronal loss in adjacent structures or fiber tracts, is critical for the effect.

Animals↗

PubMed2001

Conditional discriminations based on external and internal cues in rats with cytotoxic hippocampal lesions.

Septal-hippocampal system lesions, mostly using aspiration techniques, have been reported to impair performance of conditional tasks. Rats with axon-sparing cytotoxic hippocampal lesions were therefore tested in a range of instrumental conditional paradigms. They did not differ from controls in their ability to choose the appropriate object in a conditional object discrimination cued by internal state (hunger or thirst) or on performance of conditional visuospatial object discriminations. Acquisition of a conditional visuospatial discrimination with black and white boxes as stimuli was also unimpaired. In contrast, lesioned rats were profoundly impaired on an open T-maze task when cued by either their internal state (reference memory task) or their previous response (working memory task). The results indicate that perception or use of spatial cues, rather than conditional responding per se, is impaired by cytotoxic hippocampal lesions.

Abortion, Habitual↗

PubMed2000

Rats with hippocampal lesions learn about allocentric place cues in a non-navigational task.

Hippocampal-lesioned rats (HPC) and sham controls (SH) learned constant-negative visual discriminations among scenes in a Y-maze. Any arm could be start arm for a trial. Two choice scenes ("constant" and "variable") were shown in the other arms. In Experiment 1, each problem had 2 constants. One or the other constant appeared on every trial, and the variable changed every trial; choosing the variable was rewarded. There were 4 problem types. Each constant might be always in a given direction from the start arm (added egocentric [Ego] cue), always in a given maze arm (added allocentric [Allo] cue), both, or neither. SH rats' visual learning was enhanced by Ego and by Allo cues. HPC rats' visual learning was enhanced by Ego cues, and by Allo cues, but only if there was no Ego cue. Experiment 2 confirmed that Allo cues helped HPC rats as much as SH, in the absence of Ego cues. Rats with HPC lesions can learn about allocentric place cues when navigation and idiothetic cue control are not required.

Animals↗

PubMed1999

Double dissociation of function within the hippocampus: a comparison of dorsal, ventral, and complete hippocampal cytotoxic lesions.

Rats with complete cytotoxic hippocampal lesions exhibited spatial memory impairments in both the water maze and elevated T maze. They were hyperactive in photocell cages; swam faster in the water maze; and were less efficient on a nonspatial, differential reinforcement of low rates (DRL) task. Performance on both spatial tasks was also impaired by selective dorsal but not ventral lesions; swim speed was increased by ventral but not dorsal lesions. Both partial lesions caused a comparable reduction in DRL efficiency, although these effects were smaller than those of complete lesions. Neither partial lesion induced hyperactivity when rats were tested in photocell cages, although both complete and ventral lesion groups showed increased activity after footshock in other studies (Richmond et al., 1999). These results demonstrate possible functional dissociations along the septotemporal axis of the hippocampus.

Analysis of Variance↗

PubMed1999

Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning.

Rats with complete excitotoxic hippocampal lesions or selective damage to the dorsal or ventral hippocampus were compared with controls on measures of contextually conditioned freezing in a signaled shock procedure and on a spatial water-maze task. Complete and ventral lesions produced equivalent, significant anterograde deficits in conditioned freezing relative to both dorsal lesions and controls. Complete hippocampal lesions impaired water-maze performance; in contrast, ventral lesions improved performance relative to the dorsal group, which was itself unexpectedly unimpaired relative to controls. Thus, the partial lesion effects seen in the 2 tasks never resembled each other. Anterograde impairments in contextual freezing and spatial learning do not share a common underlying neural basis; complete and ventral lesions may induce anterograde contextual freezing impairments by enhancing locomotor activity under conditions of mild stress.

Analysis of Variance↗