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Norepinephrine infused into the basolateral amygdala posttraining enhances retention in a spatial water maze task.

Recent evidence indicates that the amygdala plays a role in modulating memory processes in other brain regions. For example, posttraining intra-amygdala infusions of amphetamine enhanced memory in both spatial and cued training water maze tasks; these tasks are known to depend on the integrity of the hippocampus and caudate nucleus, respectively. To determine whether this modulation is dependent on noradrenergic activation within a subregion of the amygdala (the basolateral nucleus), the present study examined the effects of posttraining microinfusions (0.2 microl) of norepinephrine or propranolol into the basolateral amygdala immediately following training in a spatial version of the water maze task. Rats received a four-trial training session on each of 2 consecutive days. On the third day, rats were given a 60-s probe test in the absence of a platform. Retention latencies obtained on the second training day revealed that norepinephrine dose-dependently enhanced retention for the location of the hidden platform. In contrast, propranolol significantly impaired retention. Probe trial analysis revealed that rats treated with 0.25 microg norepinephrine demonstrated a selective spatial bias for the training platform location relative to all other groups. These findings are consistent with others and support the view that the basolateral amygdala has a role in modulating memory storage by interacting with other brain regions.

Amygdala↗

Effects of glucose on scopolamine-induced learning deficits in rats performing the Morris water maze task.

In order to assess the effects of glucose on drug-induced spatial learning deficits, three experiments were conducted using the Morris water maze. Scopolamine and glucose were injected ip at various stages of training. Rats of Wistar strain served as subjects. In Experiment 1, scopolamine (0.4 mg/kg) and 10, 100, or 500 mg/kg of glucose were administered every day from the start of training, and the effect on acquisition was evaluated. In Experiment 2, scopolamine and 100 or 500 mg/kg of glucose were administered after 6 days of training, and the effect on performance was assessed. In Experiment 3, scopolamine and 500 mg/kg of glucose were injected after 2 days of training, and the effect on the following trial was tested. In all experiments, scopolamine impaired acquisition/performance of the task. Glucose at 500 mg/kg showed a significant enhancing effect on acquisition regardless of scopolamine injection only when injected daily from the start of training (Experiment 1). Glucose injected after the performance has reached asymptote (Experiment 2) did not affect performance, and glucose in the middle of training showed a slight but insignificant enhancing effect (Experiment 3). These results may suggest that the effect of glucose changes as a function of the degree of learning of the spatial learning task. The possibility of task specificity of the glucose effect was also discussed in relation to the cholinergic systems and local cerebral glucose utilization.

Animals↗

Phthalic acid amygdalopetal lesion of the nucleus basalis magnocellularis induces reversible memory deficits in rats.

The basolateral amygdala (BLA) is extensively implicated in emotional learning and memory. The current study investigated the contribution of cholinergic afferents to the BLA from the nucleus basalis magnocellularis in influencing aversive learning and memory. Sprague-Dawley rats were given permanent unilateral phthalic acid (300 ng) lesions of the nucleus basalis magnocellularis and were chronically implanted with cannulas aimed at the ipsilateral BLA. Lesioned rats showed a pronounced inhibitory avoidance task retention deficit that was attenuated by acute posttraining infusions of the muscarinic cholinergic agonist oxotremorine (4 ng) or the indirect agonist physostigmine (1 microg) into the BLA. Continuous multiple-trial inhibitory avoidance training and testing revealed that lesioned rats have a mild acquisition deficit, requiring approximately 1 additional shock to reach the criterion, and a pronounced consolidation deficit as indicated by a shorter latency to enter the shock compartment on the retention test. Because lesioned rats did not differ from sham-operated controls in performance on a spatial water maze task or in shock sensitivity, it is not likely that the memory impairments produced by the phthalic acid lesions are due to any general sensory or motor deficits. These findings suggest that the dense cholinergic projection from the nucleus basalis magnocellularis to the BLA is involved in both the acquisition and the consolidation of the aversive inhibitory avoidance task.

Amygdala↗

Spatial learning and memory is preserved in rats after early development in a microgravity environment.

This study evaluated the cognitive mapping abilities of rats that spent part of their early development in a microgravity environment. Litters of male and female Sprague-Dawley rat pups were launched into space aboard the National Aeronautics and Space Administration space shuttle Columbia on postnatal day 8 or 14 and remained in space for 16 days. These animals were designated as FLT groups. Two age-matched control groups remained on Earth: those in standard vivarium housing (VIV) and those in housing identical to that aboard the shuttle (AGC). On return to Earth, animals were tested in three different tasks that measure spatial learning ability, the Morris water maze (MWM), and a modified version of the radial arm maze (RAM). Animals were also tested in an open field apparatus to measure general activity and exploratory activity. Performance and search strategies were evaluated in each of these tasks using an automated tracking system. Despite the dramatic differences in early experience, there were remarkably few differences between the FLT groups and their Earth-bound controls in these tasks. FLT animals learned the MWM and RAM as quickly as did controls. Evaluation of search patterns suggested subtle differences in patterns of exploration and in the strategies used to solve the tasks during the first few days of testing, but these differences normalized rapidly. Together, these data suggest that development in an environment without gravity has minimal long-term impact on spatial learning and memory abilities. Any differences due to development in microgravity are quickly reversed after return to earth normal gravity.

Animals↗

The effects of aging and dorsal hippocampal lesions: performance on spatial and nonspatial comparable versions of the water maze.

Aged intact and young hippocampal-lesioned rats show similar deficits on the spatial water maze. However, this does not necessitate that the source of these deficits in the aged animals is due to hippocampal damage. These water maze deficits may arise from other aging factors such as changes in thermoregulation, muscle fatigue, swim ability, and response to stress. Consequently, it is imperative to examine the performance of aged rats on a comparable nonhippocampal version of this task. Past attempts to develop a hippocampus-independent version of the water maze were confounded because these tasks were easier (i.e., the rats spent much less time swimming in the water) than the spatial versions of the task. The current study examined performance on a hippocampus-independent task comparable in difficulty to the spatial water one. Middle-aged (16-m) and old (25-m) male F344 rats were given sham or dorsal hippocampus lesions and tested on both a spatial and a nonspatial water maze. The middle-aged rats with hippocampal lesions were impaired on the spatial task but not on the nonspatial task. Conversely, aged animals showed a similar impairment on both types of water maze tasks. Additionally, hippocampal lesions exacerbated the age-related impairment on both tasks. These findings indicate that caution must be used when interpreting the results of water maze tasks for aged animals.

Aging↗

Place learning in scopolamine-treated rats: the roles of distal cues and catecholaminergic mediation.

Experiments 1 and 2 tested the hypothesis that cholinergic receptor antagonists impair place learning in a water maze by interfering with the processing of distal, visual cues. Extramaze cues were offered to rats in the form of geometrical patterns arranged on the inner circumference of a curtain surrounding the water maze. In Experiment 1 the animals were offered both the distal cues and proximal cues in the form of pingpong balls in fixed positions on the surface of the water while only distal cues were present in Experiment 2. Animals were injected with either scopolamine (0.5 mg/kg body wt) or saline 20 min prior to the daily place learning sessions. Upon reaching criterion level performance the animals were tested on "rotation" sessions on which the distal cues were displaced. The outcome of such "rotations" demonstrated that-regardless of the presence or absence of proximal cues-scopolamine-treated rats relied at least as much as normal animals on the distal cues. The acquisition phase of both Experiments 1 and 2 demonstrated an almost complete lack of scopolamine-associated impairment in acquisition and performance of the place learning task. In Experiment 3 (when scopolamine was no longer administered) the subjects of Experiment 2 were exposed to a series of pharmacological "challenges" of their place learning performance and eventually to surgical ablation of the anteromedial prefrontal cortex. The outcome of the pharmacological challenges and the postoperative test of task performance demonstrated that the place learning performance of animals which had acquired the task under scopolamine was mediated by a neural substrate dissimilar to the substrate of task performance in normal animals. Rats acquiring the task while deprived of the cholinergic system demonstrated above-normal contributions to task mediation from catecholaminergic-probably dopaminergic-mechanisms and tentative results pointed to a "shift" toward prefrontal task mediation.

Animals↗

Proximal versus distal cue utilization in spatial navigation: the role of visual acuity?

Proximal versus distal cue use in the Morris water maze is a widely accepted strategy for the dissociation of various problems affecting spatial navigation in rats such as aging, head trauma, lesions, and pharmacological or hormonal agents. Of the limited number of ontogenetic rat studies conducted, the majority have approached the problem of preweanling spatial navigation through a similar proximal-distal dissociation. An implicit assumption among all of these studies has been that the animal's visual system is sufficient to permit robust spatial navigation. We challenged this assumption and have addressed the role of visual acuity in spatial navigation in the preweanling Fischer 344-N rat by training animals to locate a visible (proximal) or hidden (distal) platform using double or null extramaze cues within the testing environment. All pups demonstrated improved performance across training, but animals presented with a visible platform, regardless of extramaze cues, simultaneously reached asymptotic performance levels; animals presented with a hidden platform, dependent upon location of extramaze cues, differentially reached asymptotic performance levels. Probe trial performance, defined by quadrant time and platform crossings, revealed that distal-double-cue pups demonstrated spatial navigational ability superior to that of the remaining groups. These results suggest that a pup's ability to spatially navigate a hidden platform is dependent on not only its response repertoire and task parameters, but also its visual acuity, as determined by the extramaze cue location within the testing environment. The standard hidden versus visible platform dissociation may not be a satisfactory strategy for the control of potential sensory deficits.

Aging↗

Hippocampal formation lesions impair performance in an odor-odor association task independently of spatial context.

The rodent hippocampal system is known to play an important role in memory. Evidence that this role is not limited to spatial memory has come from studies using a variety of non-spatial memory tasks. One example is the social transmission of food preference paradigm, a task in which rats learn an odor-odor association with no explicit spatial memory component. However, because training and testing in this task typically take place in the same environment, it is possible that memory for the spatial context in which odors are experienced during training is critical to subsequent retention performance. If this is the case, it might be expected that lesions of the hippocampal system would impair memory performance by disrupting the establishment of a representation of the training environment. We addressed this issue by training rats in one spatial context and then testing them either in the same or a different spatial context. Normal control rats performed equally well when tested in an environment that was the same or different from that used during training, and the retention impairment exhibited by rats with hippocampus plus subiculum lesions was equivalent in the two test environments. These results support the view that the hippocampal system is necessary for the flexible expression of nonspatial memories even when the spatial context in which the memory is acquired is not critical to retrieval.

Animals↗

Effects of in utero methylmercury exposure on a spatial delayed alternation task in monkeys.

Adult female monkeys (Macaca fascicularis) were exposed to 0, 50, 70, or 90 micrograms/kg/day of methylmercury prior to and throughout pregnancy and produced 11, 9, 2, and 2 infants, respectively. At birth, blood mercury levels of treated infants ranged from 1.04 to 2.46 ppm. At approximately 7 to 9 years of age, the monkeys were trained by successive approximation to respond on a lit button for a small amount of apple juice. The monkeys were then trained on a 0.1-sec spatial delayed alternation task to a specified criterion of performance. This was followed by 10 sessions each of fixed delay times of 0.5, 1, 3, 5, and 10 sec, followed by 20 sessions containing variable delay times of 0.1 to 15 sec. Data from all treated monkeys were combined. There were no differences between treated and control monkeys in initial button training or number of sessions to reach criterion on 0.1-sec delay procedure. On the fixed delay sessions, the treated monkeys had significantly more correct trials, and fewer incorrect responses, perseverative responses, and delay responses than controls. There were no differences between the treated and control monkeys on performance on the variable delay schedule. Results from this study indicate that in utero methylmercury exposure did not adversely affect the spatial memory of adult monkeys when tested on a delayed alternation task and may have facilitated performance on this task.

Animals↗

The pattern ERG in response to colored stimuli.

The pattern-evoked electroretinogram (PERG) was studied in response to square-wave stripe patterns contrasting either between dark and colored stripes ("red-black" or "green-black" luminance contrast pattern) or between the two colors (red-green chromatic contrast pattern). All lights were matched in photopic luminance. A two-channel Maxwellian view system was used to present the stimuli in the onset-offset mode. When no pattern was present a mixture of both colors was seen. Different spatial frequencies were studied and the amplitudes of the onset response were evaluated. When the two luminance contrast patterns were presented, the responses showed a spatial selectivity. However the combination of the two colors (red-green contrast) resulted in a monotonic decrease of the response with spatial frequency. The spatially selective behavior of the response to luminance contrast patterns could be associated with the on-off center-surround organization of retinal receptive fields. The behavior of the response to chromatic-contrast patterns, on the other hand, could be explained by the action of color-opponent center-surround receptive fields as described in the primate.

Color Perception↗

Morphine conditioned place preference and locomotion: the effect of confinement during training.

The effect of confinement during conditioning on subsequent test levels of locomotor activity and conditioned place preference (CPP) was investigated by giving rats discrimination training with morphine and saline in the presence of different tactile floor cues in an open field. Groups of rats were trained under one of three levels of confinement (not confined, confined to 1/4, or confined to 1/16 of the open field) and tested for locomotor activity and CPP in the entire open field after receiving a saline injection. Confined rats subsequently spent less time on the morphine-paired floor cues (CS+) and were more active throughout the open field during the test than rats not confined during conditioning. Rats confined to the smallest area spent the least time on the CS+ and were the most active. It is suggested that confinement may preserve the novelty of the testing environment, which in turn may interfere with rats' usual responses to incentive drug-paired stimuli. These findings may have important implications for versions of the CPP technique in which training and testing environments differ considerably.

Animals↗

Spontaneous alternation, motor activity, and spatial learning in hot-foot mutant mice.

Hot-foot mutant mice, characterized by defective innervation of Purkinje cells and an ataxic gait, were less active than normal mice in a T-maze. In spontaneous alternation testing with either single or multiple trials, hot-foot mutants, contrary to normal mice, did not alternate above chance. Moreover, the mutants had a higher number of errors and higher escape latencies in a water-filled Z-maze. These results indicate that in addition to motor coordination deficits, these cerebellar mutants have deficits in spatial learning and perseverate choices of maze arms.

Animals↗

Influence of the mechanical properties of a manipulandum on human operator dynamics. II. Viscosity.

The influence of the viscosity of a manipulandum used by a human operator in a position-control pursuit-tracking task was examined. An active servo-system was used to set the viscosity of a manipulandum (motor) connected to the forearm to one of seven levels ranging in a geometric series from 12 to 800 N.s/m. During each condition the viscosity of the motor was held constant by a computer while subjects tracked, by moving their forearm in the sagittal plane, a visually presented target whose position changed randomly every 1.5 s for 255 s. Nonparametric and parametric impulse response functions were calculated between the input (target) and output (position) in each tracking condition. Nonparametric analyses revealed that subjects became sluggish at higher viscosities (above 200 N.s/m) and took longer to reach the target. A second-order low-pass transfer function was found to provide a very good description of tracking performance at each viscous level. The gain and damping parameter of this transfer function were not affected by the manipulandum's viscosity, whereas both the pure delay and natural frequency of the human operator system decreased systematically with increasing manipulandum viscosity. These findings suggest that over the range of viscosities studied, there is no speed-accuracy trade-off in terms of determining an optimal level of manipulandum viscosity for a human operator, and that a less viscous interface will result in faster performance.

Adult↗

Blockade of spatial learning by the M1 muscarinic antagonist pirenzepine.

Two experiments were conducted to determine the effects of the M1 muscarinic receptor antagonist pirenzepine on place navigation in a water maze. In the first experiment rats were required to learn the location of a hidden platform following intracerebroventricular injections of equimolar doses of pirenzepine or scopolamine methylbromide. Both drugs dose-dependently impaired spatial learning according to both escape latency data and transfer test analysis. Pirenzepine was approximately 3 times less potent than scopolamine, a potency ratio which suggests M1 receptor mediation of the impairment. In the second experiment pirenzepine (1 approximately 92.3 micrograms/rat ICV) was injected prior to training on a simultaneous place discrimination task in the water maze. Impairments of choice accuracy were found with a dose of 20 micrograms/rat in the absence of any marked increases in either errors of omission or choice latency. These data suggest that M1 receptor blockade impairs processes which are involved in spatial learning.

Animals↗

Reorientation of visually evoked postural responses by different eye-in-orbit and head-on-trunk angular positions.

We examined the question of whether the position of the eyes in the head and of the head on the trunk influence the direction of visually elicited postural reactions. Normal subjects stood on a force platform viewing a large disc, rotating in the roll plane, always maintained orthogonal to the line of sight. The disc was presented at 0 degree, 30 degrees and 90 degrees to the right or left with respect to the mid-frontal plane of the subject's body and was viewed with various combinations of horizontal eye-in-orbit and head-on-trunk deviations. It was found that the main direction of body sway was always reoriented to be parallel to the disc (e.g. viewing the disc at 30 degrees oriented sway responses at a mean angle of 33 degrees). The largest sway responses were obtained when the disc was parallel to the sagittal plane of the body and was viewed with an ipsilateral eye-neck deviation totalling 90 degrees (head-on-trunk 60 degrees+eye-in-orbit 30 degrees). When eye and head deviations cancelled each other (i.e. eye-in-orbit +30 degrees combined with head-on-trunk -30 degrees), directional effects on sway also cancelled each other out. This result demonstrates that signals of eye-in-orbit and head-on-trunk position have the capability to redirect visuo-motor commands to the appropriate postural muscles. This allows vision to regulate postural balance whatever the position of the eyes in space. We speculate that this function is mediated by eye and neck proprioceptive signals (or alternatively by efference copy) with access to gain control mechanisms in the visuo-postural system.

Adult↗

Differential influence of the visual framework on end point accuracy and trajectory specification of arm movements.

In this study the influence of visual scene on both arm end point accuracy and spatial path kinematics was evaluated. Eight subjects, immersed in a virtual environment, were required to point to one of ten targets located at two distances and in five directions. Targets were presented in frameworks of different complexity. The simplest framework was constituted by a uniform background, the most complex framework was constituted by a perspective-arranged grid. In the other two conditions it consisted of lines having a direction parallel to either the subject's sagittal or frontal body axis. Movements were executed without vision of both target and framework. The results showed that pointing movements were hypometric in all conditions. No difference in end point localization was observed between movements executed after presentation of the simplest and the most complex scenes. However, hypometria significantly increased when the scene was formed by lines parallel to the subject's sagittal axis. Visual information on the scene was also used to specify hand path parameters. Trajectory curvature increased with decreasing complexity of the framework. Correspondingly, the pointing kinematics varied. Taken together, these results suggest that visual analysis of cues surrounding the target can influence both target localisation and hand path planning. However, scene complexity is directly related only to determining trajectory curvature. We conclude that planning an arm movement consists of at least two processes: target localisation and hand path specification. Environmental visual cues forming the scene are taken into account differently during the two processes.

Adult↗

On the short-term adaptation of eye saccades and its transfer to head movements.

During a sequence of eye saccades toward a target that is systematically displaced during initiation of the saccade, the oculomotor system adjusts saccadic amplitude and direction in less than 100 trials to directly reach the second target position. The goal of the present work was to test whether and under which conditions these short-term, adaptive modifications in eye movements are transferred from horizontal eye saccades to horizontal head-pointing movements. In the first series of experiments subjects had to execute head yaw rotations to an extent defined by verbal command (assessed movements). These head movements were not part of visually elicited gaze shifts. They were recorded before and after a period of saccadic adaptation. Saccades were adapted to reduced amplitudes by using target displacements from 30 to 20 degrees and from 40 to 30 degrees. After 40-50 trials per target displacement, the amount of eye saccade adaptation was 79% (30-20 degrees) and 97% (40-30 degrees) of the displacement amplitude. In the second series of experiments, visually triggered head movements to briefly illuminated targets (100 ms) were measured before and after adaptation. The data obtained from both series did not reveal a functionally significant transfer of saccadic adaptation to head movements. The amount of possible transfer given as a percentage of the amount of achieved adaptation was: assessed head movements, 40 degrees, 1.9%, 20 degrees, -8.6%; visually triggered movements, 40 degrees, 5.1%, 20 degrees, 10.0%. No values significantly deviated from zero.

Adaptation, Physiological↗