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Spatial learning of transgenic mice is often assessed in the Morris watermaze, where mice must use distant cues to locate a submerged platform. Such learning is confounded by species-specific noncognitive swimming strategies. Factor analysis permits cognitive and noncognitive strategies to be disentangled and their association with electrophysiological phenomena to be investigated.
Many observations in humans and experimental animals support the view that the hippocampus is critical immediately after learning in order for long-term memory formation to take place. However, exactly when the medial temporal cortices adjacent to the hippocampus are necessary for this process to occur normally is not yet well known. Using a spatial task, we studied whether the perirhinal cortex of rats is necessary to establish representations in long-term memory. Results showed that, in a spatial task sensitive to hippocampal lesions, control and perirhinal lesioned rats can both learn at the same rate (Experiment 1). Interestingly, a differential involvement of the perirhinal cortex in memory retention was observed as time passes after learning. Thus, 24 days following the end of learning, lesioned and control rats remembered the task perfectly as measured by a retraining test. In contrast, 74 days after the learning the perirhinal animals showed a profound impairment in the retention of the spatial information (Experiment 2). Taken together, these results suggest that the perirhinal region is critical for the formation of long-term spatial memory. However, its contribution to memory formation and retention is time-dependent, it being necessary only long after learning takes place and not during the phase immediately following acquisition.
This paper describes a neural network model that directs saccades back to targets after they disappear and other saccades intervene. This is a simple example of knowing where something is after it is no longer visible and the observer has moved. These tasks require a short-term memory that can store continuous values of spatial location. The model was generated by training a neural network with a recurrently connected hidden layer to specify memory-guided saccades. The trained network maintains stored locations accurately for a few seconds. It uses a leaky integrator mechanism in which there is a slow decay of the stored value to a small number of fixed point attractors. Similar mechanisms have been used to model oculomotor integration (Cannon, S., Robinson, D., & Shamma, S. (1983). A proposed neural network for the integrator of the oculomotor system. Biological Cybernetics, 49, 127-136; Seung, H. (1998). Continuous attractors and oculomotor control. Neural Networks, 11, 1253-1258). The mechanism is robust to parameters such as the input and output format and the constraints in training. However, the receptive field properties of the hidden units do depend on these parameters. It was possible to find biologically plausible parameters that produced hidden unit behavior similar to that of real neurons involved in saccade memory. In particular, training the model to simultaneously represent the target location in both eye- and head-based reference frames produces units similar to neurons in parietal saccade areas.
Previous research has shown that spatial, movement, and reward information is integrated within the ventral striatum (VS). The present study examined the possible contribution of the basolateral nuclei of the amygdala (BLA) to this interaction by examining behavioral correlates of BLA neurons while rats performed multiple memory trials on an 8-arm radial maze. Alternate arms consistently held 1 of 2 different amounts of reward. Recorded cells were correlated with motion, auditory input, space, and reward acquisition. Reward-related units were found that anticipated reward encounter, that responded during reward consumption, and that differentiated between high and low reward magnitude. This is consistent with the hypothesis that BLA neurons may provide the VS with reward-related information that could then be integrated with spatial information to ultimately affect goal-directed behavior.
In an attempt to evaluate whether previous training antagonizes age-related memory deficits, aged rats with previous training experience were compared with aged and young naive rats in the Morris water maze test. The findings of our study indicate that experience seems to facilitate the preservation of the spatial reference memory for 12 months in the aged rat, whereas senescent naive animals showed the usual age-related memory deficits. However, experience seems task-specific since the same aged rats fail to acquire a new different task.
Neurons with zinc in the presynaptic vesicles innervate much of the telencephalon, but the functional significance of the vesicular zinc has never been established. The present work shows that reversible binding of zinc by drug infusion into the hippocampus produces a time-locked and selective disruption of hippocampal-dependent spatial-working memory. A role for vesicular zinc in neurotransmission or neuromodulation is implied.
Within the brain, the inflammatory cytokine interleukin-1 (IL-1) mediates illness-associated neural, neuroendocrine, and behavioral responses; however, its role in normal neurobehavioral processes is not clear. To examine the role of IL-1 signaling in memory, we infused Long-Evans rats intracerebroventricularly with IL-1beta (10 ng/rat), IL-1 receptor antagonist (IL-1ra, 100 microg/rat), or saline immediately following a learning task and tested memory functioning 1-8 days later. In the Morris water maze (MWM), IL-1ra caused memory impairment in the hippocampus-dependent, spatial version, whereas IL-1beta had no effect. Neither IL-1beta nor IL-1ra influenced the hippocampus-independent, nonspatial version of the MWM. In the passive avoidance response, which also depends on hippocampal functioning, IL-1ra caused memory impairment, and IL-1beta caused memory improvement. These results suggest that IL-1 signaling within the hippocampus plays a critical role in learning and memory processes.
Effects of bilateral chemical lesion of the hippocampus was examined in 1- to 2-week-old domestic chicks. Chicks were trained and tested in an egocentric spatial task, in which subject chicks should memorize location of a rewarding object in reference to the subject's viewpoint. Two beads were simultaneously presented on a wall, and chicks pecked at one of them based on relative location (left-right or above-below) to gain a reward. Comparison of training curves revealed that the lesion significantly delayed, but did not impair, the acquisition. Recall of the spatial cue, as well as conditioning with color cues, was not impaired. Hippocampus could thus be involved in memory formation of spatial relationships between nearby objects.
Rodents in search of food use visual environmental signals and complex spatial strategies and do not return to previously-visited locations, known as the win-shift strategy. The solution to the Olton Octagonal Maze (OOM) involves Working Memory (WM). A modified OOM was used that allows for measuring WM and Long Term Memory (LTM). The delayed spatial win-shift task consisted of a Training and Test phase separated by a delay. Prior to the Training phase, four arms were chosen at random and blocked, and food pellets were placed in the food cups of the four remaining open arms. Each rat was allowed to retrieve the pellets from the four open arms and then return to its home cage for the delay period (either 5 or 20 min). In the Test phase all 8 lanes were open, and the bait was placed in those blocked in the previous phase. Two experimental groups of rats, Long Evans and Norvegicus, and their corresponding control groups were trained. The experimental subjects performed Training-Delay-Test. The controls were only trained in the Test phase. Revisiting an arm previously explored in the 1st Phase was considered a LTM error. Revisiting an arm in the same trial constituted a WM error. It was concluded that the experimental groups do in fact possess LTM, with differences in favor of Norvegicus. There was no difference with respect to WM errors. The Norvegicus control group changes its strategy from allocentric to egocentric, which did not occur in the Long Evans control group.
Review of available literature reveals the lack of reports on memory impairment in relation to visuo-spatial and tridimensional dominance. Considering the absence of specific methods for assaying evaluations, the intention of our study was to devise a systematic testing procedure in order to explore the patterns referrable to this aspect.
Human orientation and spatial cognition partly depends on our ability to remember sets of visual landmarks and imagine their relationship to us from a different viewpoint. We normally make large body rotations only about a single axis which is aligned with gravity. However, astronauts who try to recognize environments rotated in 3 dimensions report that their terrestrial ability to imagine the relative orientation of remembered landmarks does not easily generalize. The ability of human subjects to learn to mentally rotate a simple array of six objects around them was studied in 1-G laboratory experiments. Subjects were tested in a cubic chamber (n = 73) and a equivalent virtual environment (n = 24), analogous to the interior of a space station node module. A picture of an object was presented at the center of each wall. Subjects had to memorize the spatial relationships among the six objects and learn to predict the direction to a specific object if their body were in a specified 3D orientation. Percent correct learning curves and response times were measured. Most subjects achieved high accuracy from a given viewpoint within 20 trials, regardless of roll orientation, and learned a second view direction with equal or greater ease. Performance of the subject group that used a head mounted display/head tracker was qualitatively similar to that of the second group tested in a physical node simulator. Body position with respect to gravity had a significant but minor effect on performance of each group, suggesting that results may also apply to weightless situations. A correlation was found between task performance measures and conventional paper-and-pencil tests of field independence and 2&3 dimensional figure rotation ability.
The authors examined effects of structural and organizational spatial context on younger and older adults' memory for an arrangement of dollhouse furniture pieces. For half of the participants, landmark objects (Experiment 1) and a floor plan beneath the array (Experiment 2) served as structural context during study and replacement. Organizational context was varied by grouping items randomly or as 6 rooms in a prototypical house. Two study and replacement trials were given. In Experiment 1, landmark structural cues improved younger adults' performance, whereas both age groups benefited from the floor plan in Experiment 2. In both experiments, positive effects of organizational context and trial occurred. Higher order interactions further revealed that structural and organizational context effects varied in size across trials, suggesting that both age groups used spatial contextual cues more effectively with practice. Implications of these results for current views on cognitive compensation in adulthood are discussed.
Previous studies in the rat have shown that a serotonergic depletion greatly potentiates the learning and memory impairments produced by pharmacological or lesion-induced cholinergic blockade in the forebrain. The impairment produced by combined serotonergic-cholinergic lesions is reminiscent of that seen in memory-impaired aged rats. In the present experiment, we investigated whether grafts of cholinergic septal tissue and serotonergic mesencephalic raphe tissue, placed in the hippocampus, could reverse the severe memory impairment produced by combined cholinergic-serotonergic lesions. Adult rats were given an intraventricular injection of 5,7-dihydroxytryptamine followed by a radiofrequency lesion of the septum 1-2 weeks later. Three weeks after lesion surgery, the rats were given bilateral intrahippocampal cell suspension grafts of either fetal septal or mesencephalic raphe tissue, or both. The rats were tested for spatial learning and memory in the Morris water maze task at 4 and 10 months after grafting. At 4 months, lesioned and grafted groups were all impaired compared to the normal controls in their swim time and distance swum to find the platform, and they did not show any spatially focussed search strategy in the spatial probe trial when the platform was removed from the tank. At 10 months, the rats with mixed cholinergic and serotonergic grafts were no longer impaired compared to normals in their swim time and distance to find the platform, and they were significantly improved compared to the other grafted groups. Moreover, in the spatial probe trial, the rats with mixed cholinergic and serotonergic grafts displayed a spatially focussed search behaviour over the previous platform site, which was not seen in the lesioned control rats or in the other graft groups. Morphological analysis of the hippocampus revealed that the septal grafts produced an acetylcholinesterase-positive innervation but were totally devoid of serotonin innervation. The raphe grafts produced mainly a serotonin innervation, of both acetylcholinesterase- and serotonin-positive fibres. The results suggest that a mixture of septal and raphe tissue is required when grafted to the hippocampal formation in order to ameliorate the severe spatial learning and memory impairments produced by a combined cholinergic and serotonergic denervation, and that each of these graft types separately are not sufficient to ameliorate such deficits.
In this procedure, subjects learn the spatial position of one hole out of many, that allows them to escape from a large open-field into their home cage. The arena is circular and can be rotated between trials so that no proximal landmark is permanently associated with the target hole. This task is thus similar to the Morris water maze procedure, since subjects must remember the position of the escape hole relative to extra-arena cues only. In addition it allows studying the importance of olfactory cues such as scent marks in or around a hole. Since the motivation is to reach home and the motor requirement is low, this task provides a useful alternative to the Morris place navigation task for studying spatial orientation in weanling or senescent rats. Examples are given showing that various behavioural parameters provide a good estimation as how subjects learn this task.
Long-term vaccinations with human beta-amyloid peptide 1-42 (Abeta1-42) have recently been shown to prevent or markedly reduce Abeta deposition in the PDAPP transgenic model of Alzheimer's disease (AD). Using a similar protocol to vaccinate 7.5-month-old APP (Tg2576) and APP+PS1 transgenic mice over an 8-month period, we previously reported modest reductions in brain Abeta deposition at 16 months. In these same mice, Abeta vaccinations had no deleterious behavioral effects and, in fact, benefited the mice by providing partial protection from age-related deficits in spatial working memory in the radial arm water maze task (RAWM) at 15.5 months. By contrast, control-vaccinated transgenic mice exhibited impaired performance throughout the entire RAWM test period at 15.5 months. The present study expands on our initial report by presenting additional behavioral results following long-term Abeta vaccination, as well as correlational analyses between cognitive performance and Abeta deposition in vaccinated animals. We report that 8 months of Abeta vaccinations did not reverse an early-onset balance beam impairment in transgenic mice. Additionally, in Y-maze testing at 16 months, all mice showed comparable spontaneous alternation irrespective of genotype or vaccination status. Strong correlations were nonetheless present between RAWM performance and extent of "compact" Abeta deposition in both the hippocampus and the frontal cortex of vaccinated APP+PS1 mice. Our results suggest that the behavioral protection of long-term Abeta vaccinations is task specific, with preservation of hippocampal-associated working memory tasks most likely to occur. In view of the early short-term memory deficits exhibited by AD patients, Abeta vaccination of presymptomatic AD patients could be an effective therapeutic to protect against such cognitive impairments.
A neurochemical study of the transsynaptic interactions established between septal GABAergic interneurones and cholinergic septo-hippocampal neurones was conducted using mice. The effects of acute in vivo injections of either muscimol (20-500 ng/0.2 microliter), bicuculline (100 ng-1 micrograms/0.2 microliter) or saline vehicle (0.2 microliter) into the medial septum on septo-hippocampal cholinergic activity were evaluated using measures of hippocampal high affinity choline uptake at 30 min post-injection in two main groups of mice. The first (quiet control) remained in their home cages during the post-injection period whereas the second (active) were submitted, 10 min following injection to a 20-min period of spatial working memory testing in an 8-arm radial maze. Intraseptal injections of either muscimol or bicuculline produced significant (25-50%) inhibition of hippocampal cholinergic activity in quiet conditions (basal) as compared to intact or saline-injected mice. In the active groups, whereas memory testing induced significant cholinergic activation (+15-20%) in intact and saline injected mice at 30 s post-test no significant memory testing-induced activation was observed in either muscimol or bicuculline-injected mice at any dose. The role of septal GABAergic interneurones in the indirect transsynaptic control over the basal and activated states of septo-hippocampal cholinergic activity is discussed with respect to the concept that these complex neuronal interactions contribute to the physiological mechanisms involved in the modulation of working memory performance.
Stress exposure, depending on intensity and duration, elicits adaptive or maladaptive physiological changes. The same general pattern of advantageous versus deleterious stress effects appears to exist for some cognitive functions, particularly spatial learning and memory performance. This article reviews sex differences in response to stress on a variety of spatial tasks. In general, females are more resistant than males to stress-induced impairments on spatial tasks, including the radial arm maze and object placement. In young adulthood, chronic stress (restraint, 6 h per day for 21 days) impairs male performance on both tasks but leads to behavioural enhancements in females. Furthermore, these sex-dependent stress effects are influenced by both organisational and activational oestrogenic effects. Additionally, sex-specific stress responses vary depending on developmental age at the time of stress exposure. Male behavioural stress responses appear fixed across the lifespan (i.e. stress-induced cognitive impairments) whereas female stress responses appear more variable (i.e. stress-induced enhancements observed in young adulthood are different in response to prenatal stress and diminished following stress exposure at old age). These findings underscore the point that many effects obtained in males cannot be generalised to females and highlight the need to investigate the stress response at different ages and in both sexes.
Estrogen (E) treatment induces axospinous synapses in rat hippocampus in vivo and in cultured hippocampal neurons in vitro. To better explore the molecular mechanisms underlying this phenomenon, we have established a mouse model for E action in the hippocampus by using Golgi impregnation to examine hippocampal dendritic spine morphology, radioimmunocytochemistry (RICC) and silver-enhanced immunocytochemistry to examine expression levels of synaptic protein markers, and hippocampal-dependent object-placement memory as a behavioral readout for the actions of E. In ovariectomized mice of several strains and F(1) hybrids, the total dendritic spine density on neurons in the CA1 region was not enhanced by E treatment, a finding that differs from that in the female rat. E treatment of ovariectomized C57BL/6J mice, however, caused an increase in the number of spines with mushroom shapes. By RICC and silver-enhanced immunocytochemistry, we found that the immunoreactivity of postsynaptic markers (PSD95 and spinophilin) and a presynaptic marker (syntaxin) were enhanced by E treatment throughout all fields of the dorsal hippocampus. In the object-placement tests, E treatment enhanced performance of object placement, a spatial episodic memory task. Taken together, the morphology and RICC results suggest a previously uncharacterized role of E in synaptic structural plasticity that may be interpreted as a facilitation of the spine-maturation process and may be associated with enhancement of hippocampal-dependent memory.