Cholinergic input to the hippocampus is not required for a model of episodic memory in the rat, even with multiple consecutive events.

Previous work has shown that depletion of the cholinergic input to the hippocampus produces no impairment in an episodic (what-where-which) memory task in rats. However, in contrast a where-which task was significantly impaired. Models of acetylcholine function related to pattern separation were used to explain this result. Recent development of spontaneous recognition tasks to assess multiple trials consecutively in the same testing session allow an opportunity to assess whether an increase in interference produces an impairment in the episodic memory task using the same cholinergic lesion. By increasing the number of trials happening consecutively the proactive interference between events being remembered increases, with the prediction that a reduction in pattern separation as a result of reduced acetylcholine in the hippocampus would now produce an impairment in this task. We show that a continual trials approach to the episodic memory task has no impact on the effects of cholinergic depletion of the hippocampus, with effects mirroring those from using just one trial a day approaches to these tasks. We suggest that pattern separation models of acetylcholine function can still explain our findings, but with an apparent emphasis on context-specific locations rather than all types of memory.

Moving beyond standard procedures to assess spontaneous recognition memory.

This review will consider how spontaneous tasks have been applied alongside neuroscientific techniques to test complex forms of recognition memory for objects and their environmental features, e.g. the spatial location of an object or the context in which it is presented. We discuss studies that investigate the roles of the perirhinal cortex and the hippocampus in recognition memory using standard testing paradigms, and consider how these findings contribute to the ongoing debate about whether recognition memory is a single unitary process or multiple processes that can be dissociated anatomically and functionally. Due to the wide use of spontaneous tasks, the need for improved procedures that reduce animal use is acknowledged, with multiple trial paradigms discussed as a novel way of reducing variability and animal numbers in these tasks. The importance of improving translation of animal models to humans is highlighted, with emphasis on a shift away from relying on the phenomenological experience of human subjects.

Putting memory in context: dissociating memories by distinguishing the nature of context.

In recent years, spontaneous recognition tasks have become commonplace methods of assessing memory in animals. Adaptations of these tasks allow us to look at the role of objects, contexts and spatial locations in memory. Recent findings have highlighted that not all types of contexts in these tasks rely on the same neural systems. Similarly, asking different questions about the same types of context can allow the dissociation of neural systems underlying these memories. Here we review the current position in how context is used in such tasks, and we consider the fundamental importance of clearly defining both the nature of the context being used, and the questions asked of it in order to fully appreciate the neural and cognitive mechanisms being studied in such tasks.

A new behavioural apparatus to reduce animal numbers in multiple types of spontaneous object recognition paradigms in rats.

Standard object recognition procedures assess animals' memory through their spontaneous exploration of novel objects or novel configurations of objects with other aspects of their environment. Such tasks are widely used in memory research, but also in pharmaceutical companies screening new drug treatments. However, behaviour in these tasks may be driven by influences other than novelty such as stress from handling which can subsequently influence performance. This extra-experimental variance means that large numbers of animals are required to maintain power. In addition, accumulation of data is time consuming as animals typically perform only one trial per day. The present study aimed to explore how effectively recognition memory could be tested with a new continual trials apparatus which allows for multiple trials within a session and reduced handling stress through combining features of delayed nonmatching-to-sample and spontaneous object recognition tasks. In this apparatus Lister hooded rats displayed performance significantly above chance levels in object recognition tasks (Experiments 1 and 2) and in tasks of object-location (Experiment 3) and object-in-context memory (Experiment 4) with data from only five animals or fewer per experimental group. The findings indicated that the results were comparable to those of previous reports in the literature and maintained statistical power whilst using less than a third of the number of animals typically used in spontaneous recognition paradigms. Overall, the results highlight the potential benefit of the continual trials apparatus to reduce the number of animals used in recognition memory tasks.

The roles of perirhinal cortex, postrhinal cortex, and the fornix in memory for objects, contexts, and events in the rat.

Investigation of the anatomical substructure of the medial temporal lobe has revealed a number of highly interconnected areas, which has led some to propose that the region operates as a unitary memory system. However, here we outline the results of a number of studies from our laboratories, which investigate the contributions of the rat's perirhinal cortex and postrhinal cortex to memory, concentrating particularly on their respective roles in memory for objects. By contrasting patterns of impairment and spared abilities on a number of related tasks, we suggest that perirhinal cortex and postrhinal cortex make distinctive contributions to learning and memory: for example, that postrhinal cortex is important in learning about within-scene position and context. We also provide evidence that despite the strong connectivity between these cortical regions and the hippocampus, the hippocampus, as evidenced by lesions of the fornix, has a distinct function of its own--combining information about objects, positions, and contexts.

Dissociable effects of lesions to the perirhinal cortex and the postrhinal cortex on memory for context and objects in rats.

Memory for the context in which an object appeared was investigated with a version of the spontaneous object recognition paradigm. Sham-operated rats explore familiar objects appearing in incongruent but familiar contexts more than those appearing in congruent contexts, revealing memory for the context in which an object previously appeared. At short delays, perirhinal cortex-lesioned rats were unimpaired on memory for object in context, whereas fornix-lesioned rats showed only a mild impairment. In contrast, postrhinal lesions resulted in severe deficits. However, in a comparable noncontextual object task, postrhinal and fornix lesions had no effect, whereas perirhinal-lesioned rats were severely impaired. Comparison of these tasks and other published data may shed light on the nature of the contextual processing involved.

Objects and positions in visual scenes: effects of perirhinal and postrhinal cortex lesions in the rat.

The authors assessed rats' encoding of the appearance or egocentric position of objects within visual scenes containing 3 objects (Experiment 1) or 1 object (Experiment 2A). Experiment 2B assessed encoding of the shape and fill pattern of single objects, and encoding of configurations (object + position, shape + fill). All were assessed by testing rats' ability to discriminate changes from familiar scenes (constant-negative paradigm). Perirhinal cortex lesions impaired encoding of objects and their shape; postrhinal cortex lesions impaired encoding of egocentric position, but the effect may have been partly due to entorhinal involvement. Neither lesioned group was impaired in detecting configural change. In Experiment 1, both lesion groups were impaired in detecting small changes in relative position of the 3 objects, suggesting that more sensitive tests might reveal configural encoding deficits.

Impaired object recognition with increasing levels of feature ambiguity in rats with perirhinal cortex lesions.

It has been proposed that the perirhinal cortex is involved in the representation of the characteristics of objects. In particular it has been proposed that it is critical for discriminating between stimuli which have some features in common and thus it has been described as being involved in resolving feature ambiguity. The present experiments demonstrate that lesions of perirhinal cortex in the rat cause impairments in object recognition which increase with the level of feature ambiguity present in the discrimination. Although increasing feature ambiguity increases the overall difficulty of discriminations, lesions of the perirhinal cortex resulted in a disproportionate impairment when feature ambiguity was increased and not when the difficulty of the discrimination was increased through enlargement of the stimulus set. The present experiments therefore support the view that perirhinal cortex in the rat is critical to resolution of feature ambiguity in stimulus specification.

The role of perirhinal cortex in visual discrimination learning for visual secondary reinforcement in rats.

Perirhinal cortex in monkeys has been thought to be involved in visual associative learning. The authors examined rats' ability to make associations between visual stimuli in a visual secondary reinforcement task. Rats learned 2-choice visual discriminations for secondary visual reinforcement. They showed significant learning of discriminations before any primary reinforcement. Following bilateral perirhinal cortex lesions, rats continued to learn visual discriminations for visual secondary reinforcement at the same rate as before surgery. Thus, this study does not support a critical role of perirhinal cortex in learning for visual secondary reinforcement. Contrasting this result with other positive results, the authors suggest that the role of perirhinal cortex is in "within-object" associations and that it plays a much lesser role in stimulus-stimulus associations between objects.

Nimodipine prevents scopolamine-induced impairments in object recognition.

The effects of acute administration of the dihydropyridine calcium channel antagonist, nimodipine, were studied on the actions of scopolamine in the object recognition test. Scopolamine at 0.125 mg/kg decreased the difference in the time spent exploring novel and familiar objects when given either 15 min before, or immediately after, exposure to objects. Administration of nimodipine at 10 mg/kg, or 1 mg/kg, at the same time as the scopolamine completely prevented the deleterious effects on memory in this task. This effect was seen when nimodipine and/or scopolamine were given prior to the object exposure and also when the drugs were given after the experience of seeing the objects. Nimodipine had no effects on performance when given in the absence of scopolamine. This lack of change in total time spent exploring the objects indicated that the effects of scopolamine and nimodipine were not due to changes in motor coordination or alertness. The results are discussed in the light of the role of cholinergic transmission in memory and the known actions of dihydropyridines on brain function.

Elemental and configural visual discrimination learning following lesions to perirhinal cortex in the rat.

Rats were tested in a series of two-choice visual discrimination tasks in a computer-controlled testing apparatus. The discriminations used a range of discriminanda, which varied in complexity. The discriminations included relatively simple form discriminations, more complex form discriminations and discriminations between compound stimuli that shared many features. It was found that rats with perirhinal cortex lesions were unimpaired in all discriminations except those that involved the compound stimuli with overlapping features. Using these stimuli, rats with perirhinal cortex lesions were unimpaired when the stage of learning did not necessitate discriminating stimuli on the basis of more than one feature. However, when efficient performance of the task needed the configuration of more than one feature to be taken into account, perirhinal lesioned rats were impaired. These results are interpreted as revealing the role of the perirhinal cortex in providing multifeature information about the properties of visual objects.

Perirhinal cortex ablation in rats selectively impairs object identification in a simultaneous visual comparison task.

In Experiment 1, rats discriminated among computer-generated visual displays (scenes) comprising 3 different shapes (objects). One constant scene (unrewarded) appeared on every trial together with a trial-unique variable scene (rewarded). Four types of variable scene were intermingled: (a) unfamiliar objects in different positions from the constant; (b) unfamiliar objects in same positions as the constant; (c) same objects as the constant in different positions; (d) same objects and positions, recombined. Aspiration lesions of perirhinal cortex impaired performance with type (b) only. Experiment 2 tested spatial delayed nonmatching-to-sample. The perirhinal group were impaired nonsignificantly, and less than fornix-transected rats in an earlier study. Rats' perirhinal cortex, like monkeys', subserves object identification in the absence of memory requirement but does not contribute substantially to hippocampal system spatial memory function.

Childhood amnesia: on answering questions about very early life events.

Twenty five young adults were asked about the events surrounding the birth of a younger sibling which took place when they were under the age of 2 years. Approximately 40% of the participants claimed to have significant memories of the events. The mothers of our participants verified that a majority of their answers were accurate. Comparing the pattern of data with those previously collected (Eacott & Crawley, 1998) suggests that the memories of those who were aged below 2:0 are qualitatively similar to the memories of those who were older at the time of events and dissimilar in type to those who are basing their reports on reconstructions from family knowledge. This finding may be evidence that memories of events that occurred before the age of 2 years are genuine but rare. This conclusion may be useful in assessing theories of childhood amnesia.

The offset of childhood amnesia: memory for events that occurred before age 3.

Adult memory for the events surrounding the birth of a sibling was examined in 69 adults. The authors identified a steep offset for childhood amnesia for this event before the child reaches age 2 1/2 years. The authors also examined the accuracy of information recalled. Although the majority of the answers were accurate, false memories were a consistent feature of the data. Alternative explanations of the authors' data were considered by examining the amount of information an additional 57 adults had about a family birth for which they could have no memory. The pattern of results did not support the view that participants might be unable to differentiate between memories and knowledge about the event.

Ventral prefrontal cortex is not essential for working memory.

It is widely held that the prefrontal cortex is important for working memory. It has been suggested that the inferior convexity (IC) may play a special role in working memory for form and color (). We have therefore assessed the ability of monkeys with IC lesions to perform visual pattern association tasks and color-matching tasks, both with and without delay. In experiment 1, six monkeys were trained on a visual association task with delays of up to 2 sec. Conservative IC lesions that removed lateral area 47/12 in three animals had no effect on the task. Further experiments showed that these lesions had no effect on the postoperative new learning of a color-matching task with delays of up to 2 sec or versions of the visual association task involving delays of up to 8 sec. In experiment 2, larger lesions of both areas 47/12 and 45A were made in the three control animals. This lesion caused a profound deficit in the ability to relearn simultaneous color matching, but subsequent matching with delays of up to 8 sec was clearly unimpaired. We suggest that the IC may be more important for stimulus selection and attention as opposed to working memory.

Spatial memory impairment in rats with fornix transection is not accompanied by a simple encoding deficit for directions of objects in visual space.

In Experiment 1, rats learned 6 discriminations among pairs of complex wide-angle visual displays, presented concurrently, using a computer-controlled Y maze. Fornix-transected rats were unimpaired relative to controls regardless of whether the displays comprised a single large "objectlike" figure or "scenelike" arrays of spatially distributed figures. Experiment 2 compared 2 versions of a visual discrimination in which either object identity (independent of location within the visual field) or location within the visual field (independent of object identity) had to be used. The fornix-transected rats performed normally with either cue. In Experiment 3, however, the same group was clearly impaired on a standard spatial memory test, spatial delayed nonmatching to sample. Although the fornix-transected rats were more likely to choose rapidly and inaccurately, their deficit was not a by-product of impulsive responding. The spatial impairment was not merely a difficulty in encoding direction of a single item within visual space, but more complex configural deficits could not be ruled out.

The recognition memory deficit caused by mediodorsal thalamic lesion in non-human primates: a comparison with rhinal cortex lesion.

Two earlier studies found that rhinal cortex ablations in the monkey (Macaca fascicularis) impaired delayed matching-to-sample (DMS) when the stimuli in the experiment came from a large population of possible stimuli, but not when the stimulus population was small, while uncinate fascicle section had no effect on DMS whatever the stimulus population size. The mediodorsal thalamus receives a large projection from the rhinal cortex, and has been implicated in recognition memory performance. We trained monkeys preoperatively in delayed matching-to-sample with large and small stimulus populations, exactly as in the earlier studies, then examined the effect of bilaterally ablating the medial portion of the mediodorsal thalamic nucleus. Mediodorsal lesion impaired postoperative delayed matching-to-sample performance with a large stimulus set, but had no effect on performance of DMS with a small stimulus population. In comparison with the earlier data from rhinal cortex lesions with the same methods, wherever a deficit was seen in the rhinal-lesioned animals the mediodorsal thalamic nucleus-lesioned animals showed a smaller deficit. We conclude that other efferents from the rhinal cortex, possibly those to the adjacent inferior temporal cortex, enable better performance in the mediodorsal thalamic nucleus-lesioned animals than in the animals with rhinal cortex ablation.

Visual learning for an auditory secondary reinforcer by macaques is intact after uncinate fascicle section: indirect evidence for the involvement of the corpus striatum.

Three cynomolgus monkeys (Macaca fascicularis) were trained preoperatively in visual discrimination learning for an auditory secondary reinforcer. Each new discrimination problem was solved on the basis of the secondary reinforcer, and primary reinforcement (food reward) was given only after a new problem had been solved. The animals learned 50 new problems in each daily session and it was therefore possible to assess accurately their average rate of learning new discrimination problems in this procedure. After the learning rate had stabilized preoperatively the animals were operated upon to transect the uncinate fascicle, the cortico-cortical pathway from visual association cortex in the temporal lobe to prefrontal cortex. The animals' learning rate was unchanged after uncinate fascicle section. A previous experiment has shown that visual learning for an auditory secondary reinforcer is unaffected by disconnection of visual association cortex from the amygdala and the fornix. Taken together, this negative evidence points strongly to the conclusion that visual learning for an auditory secondary reinforcer depends upon interaction of temporal lobe visual association cortex with the corpus striatum, since other possibilities have been excluded.

A computer-controlled maze environment for testing visual memory in the rat.

A computer-controlled version of a Y-maze was developed to allow automated testing of rats' learning and memory with visual stimuli. Each of the 3 arms terminated with 2 adjacent monochromatic screens, 43 cm from the maze centre, providing a total stimulus area 47 cm wide by 18.5 cm high. The displays were abstract patterns extending across 2 screens, generated by algorithms which provided a large pool of discriminable patterns. The patterns used were of 2 general classes: Scenes (internally complex patterns with varying numbers of foreground shapes distributed across contrasted backgrounds) and Objects (internally homogeneous single figures, confined to the central part of the display). They could be stationary or have oscillatory movement. Subjects' location in the maze was monitored by infrared beam photodetectors; approach to correct patterns was rewarded with food. Pigmented rats of the Hooded Lister and Dark Agouti strains were tested. All could acquire 2-pair concurrent visual discriminations comprising 2 positive and 2 negative patterns, either Scenes or Objects; most could acquire 4-pair discriminations. Dark Agouti rats generally performed better than Hooded Listers. A novel training procedure using one positive and many negative patterns resulted in rapid learning of novel discriminations with either moving or non-moving patterns. The apparatus is an effective environment for visual learning by rats, suitable for a wide range of tasks in neuropsychology and psychopharmacology.

Perception and memory: action and interaction.

Receptive field properties of neurons in, and the effects of cortical ablation of, inferior regions of the macaque temporal lobe reveal their role in the visual representation of objects. However, changes in receptive field properties, as a result of visual experience with specific objects or patterns, suggest that cells encode both sensory and mnemonic features of a visual stimulus. Thus, in addition to selectivity for the visual qualities of a stimulus, response properties of cells indicate their involvement with mechanisms of visual associative and visual recognition memory. Recently, ablation studies have extended the putative role of these neurons in memory. These results suggest that the anterior inferotemporal cortex not only plays a role in recognition memory by signaling novelty or familiarity and in coding for visual associative memory but also modifies responses of neurons to the stimuli themselves, playing a part in the visual learning that underlies sensory classification of complex visual discriminanda.