Age effects in the acquisition and retention of active and passive avoidance learning by rats

Three groups of 8 male albino rats within each of the age ranges 24, 50, and 100 days were trained on an active avoidance task to a criterion of 10 successive avoidances. The number of trials to criterion was found to be a monotonic function of age. One group at each age was tested immediately thereafter for passive avoidance of the conditioning chamber, another group was tested for passive avoidance after 25 days, and the third was tested for retention of active avoidance after 25 days. Groups at 50, 75, and 125 days were used as controls for the active avoidance retention groups. All animals took significantly fewer trials to relearn the active avoidance after 25 days than did controls on the acquisition of the original learning task. On passive avoidance 24-day olds performed less efficiently than the older groups and failed to show any retention after 25 days.     

Developmental aspects of passive and active avoidance learning in rats

In Experiment 1, groups of rats 16, 19, 25, 32, and 90 to 120 days of age, were tested for retention of a passive avoidance response 2 min or 24 hr following a single training trial. Passive avoidance learning improved markedly with age, and retention over a 24-hr interval was complete for all age groups. In Experiment 2, rats 19, 25, 32, and 90 to 120 days of age were trained in a simple, active avoidance task. A trials-to-criterion measure indicated that learning was relatively independent of age, although 19-day rats were somewhat inferior to older rats. The occurrence of differences in passive avoidance learning through developmental ranges in age where simple active avoidance is little affected suggests that inhibition of responding may be selectively influenced by maturational variables.     

Ontogeny of passive avoidance: Role of task demands and development of species-typical behaviors

Preweanling rats 10 to 15 days of age were given passive avoidance training in a circular chamber in which the floor comprised one shock electrode and the wall the other. All ages showed acquisition of the response, but both rate of learning and asymptotic performance increased with age. Yoked-shock controls, adaption controls, and naive controls did not demonstrate passive avoidance on subsequent test trials, ruling out alternative interpretations based on sensitization to shock, fatigue, familiarity with the apparatus, and handling. From 10 to 15 days of age, improved performance was due in part to the transition from stereotyped shock-elicited behavior in the younger pups to discrete withdrawal from shock in the older pups. A paradoxical deterioration of performance was observed from 20 to 25 days of age, attributable to the development of species-typical defense reactions which were incompatible with the avoidance response. Retention of the avoidance response was found to increase from about 6 hr in the 10-day-old to at least 5 days in the 15-day-old. The data suggest that maturation of storage and/or retrieval mechanisms, rather than perceptual or experiential changes induced by development, is responsible for improved retention during ontogeny.     

Assessment of cognitive function following magnesium therapy in the traumatically injured brain.

Many studies have examined the preclinical efficacy of Mg2+ therapy in models of traumatic brain injury. However, more of these studies have examined sensorimotor and motor performance than cognitive performance following injury. The present paper reviews the use of Mg2+ therapy to facilitate cognitive recovery in several models of cortical injury in the rodent. The first study examined the ability of daily injections of MgCl2 (1 or 2 mmol) to impair acquisition of a reference memory task in the Morris Water Maze. Additional studies examined the ability of MgCl2 to improve cognitive function following bilateral anterior medial cortex ablations, bilateral frontal cortex contusions, and unilateral frontal contusions. The results from these studies indicate that MgCl2 therapy is biologically active and readily crosses the blood-brain barrier because daily injections of MgCl2 impaired learning of a reference memory task in intact rats. Mg2+ therapy for brain injury revealed that administration of post-injury MgCl2 effectively improved recovery of cognitive deficits following injury. These results suggest that Mg2+ therapy is effective in facilitating cognitive recovery of function following brain injury; however, there are task and dose-dependent aspects to this recovery.     

Age increases vulnerability to bacterial endotoxin-induced behavioral decrements

Peripheral lipopolysaccharide (LPS) or proinflammatory cytokines produce alterations in learning, memory, and other behaviors. Additionally, research has demonstrated that factors such as dose, route of administration, species, strain, gender, and age are important modulatory factors in the effects of endotoxin exposure. Previous research from our laboratory and others indicate that LPS-induced behavioral deficits are greater in older subjects. The current study examined avoidance learning in a negatively reinforced operant procedure (i.e., two-way active avoidance conditioning) following single or repeated intraperitoneal LPS injections in 2- and 12-month-old male C57BL/6J mice. LPS-treated subjects show impaired acquisition of the task regardless of the age of the subject, as these animals performed significantly fewer avoidance responses than controls. However, the effects of LPS administration were more pronounced in the 12-month-old animals, particularly for the subjects given repeated LPS injections. These results support the hypothesis that endotoxin exposure is capable of altering performance in this task in a way that may reflect deficits in learning, and provide evidence that increased age may exacerbate these deleterious behavioral effects.     

Behavioral deficits after intrahippocampal fetal septal grafts in rats with selective fimbria-fornix lesions

Summary Fetal septal transplants have been shown to promote behavioral recovery in young adult rats with aspiration fimbria-fornix lesions, rats with septal lesions and in intact aged rats. The present study examined the behavioral impact of intrahippocampal septal cell suspension transplants (T) in young female rats that had received, 10 days earlier, either medial fimbria lesions (Group FI.T), dorsal (subcallosal) fornix lesions (Group FO.T) or these two lesions together (Group FIFO.T). Relative to rats with lesions only (groups FI, FO and FIFO), grafted rats, irrespective of lesion locus, displayed unexpected impairments in (i) a serial alternation learning task, 5 weeks and 6 months after transplantation, and (ii) in a radial maze, 7 months after transplantation. In the first alternation test, Group FIFO showed impaired performance relative to Groups FI, FO and the sham-operated controls (Group S). In the second alternation test, Groups FO.T and FO showed impaired performance relative to Groups FI.T and FI, and only the performance of Group FI did not differ from that of Group S. In the radial maze, Groups FI, FO and FIFO all showed impaired performance relative to Group S. By contrast, there were no deleterious effects of lesions or of grafts in the acquisition and retention of a step-through passive avoidance task, 10 weeks after transplantation. Our findings on the effects of selective fimbria-fornix lesions did not confirm the report that rats with FI lesions but not those with FO lesions are unable to learn a serial alternation task, nor the report that FO lesions impair passive avoidance retention. Acetylcholinesterase (AChE) histochemistry revealed that grafts were present but graft-derived innervation of the host hippocampus varied from extensive to almost non-existent in all transplant groups. AChE-positivity in the dorsal hippocampus (DH) was not related to behavioral performance. However, the grafts often grew to a considerable size within the host brain and in many rats, especially those in Group FI.T, produced moderate to extreme damage of the host DH. There was a significant positive correlation between errors in the radial maze and graft-induced DH damage but no relationship between errors and graft size. The results indicate that, after partial lesions of the fimbria-fornix, intrahippocampal septal grafts survive well but are likely to damage recipient structures and result in behavioral impairments.     

Intertrial interval manipulations and passive avoidance retention in young Long-Evans hooded rats

Results of several studies indicate that young rats generally require more training than do adults to reach comparable criterion levels of passive avoidance behavior. In addition, younger rats generally show poorer retention performance than adults. In the present study, preweanling and weanling Long-Evans rats were given passive avoidance training at intertrial intervals (ITI) of 2 min, 1 hr, or 24 hr until a 600-s criterion was obtained. A 2-week retention test also was given to each subject. Results indicate that ITI had little effect on rate of acquisition or retention. Acquisition and retention performance did improve with age, as is typically reported with other strains of rats. The present results support previous acquisition and retention studies indicating that the ability to acquire and retain a passive avoidance task for weanling and preweanling rats increases with age.     

Loss of cholinergic neurons in the nucleus basalis induces neocortical electroencephalographic and passive avoidance deficits.

The present experiments were designed to examine the hypothesis that the degeneration of cholinergic nucleus basalis is related to the cognitive and neurophysiological deficits found in old age. Aged (26 months) rats were impaired both in the acquisition of spatial (water-maze) task and retention of passive avoidance task. During aging, neocortical electroencephalographic fast activity was decreased and high-voltage spindles increased. Loss of choline acetyltransferase-positive neurons correlated with the high-voltage spindle incidence and passive avoidance retention deficit. Unilateral ibotenate nucleus basalis lesioning decreased choline acetyltransferase activity in the cortex and produced a large nonspecific subcortical cell loss in young rats. Ibotenate-lesioned rats were impaired in spatial learning and passive avoidance retention in young rats. Quisqualic acid produced a greater decrease in cortical choline acetyltransferase activity and smaller nonspecific subcortical cell loss than ibotenate lesioning. Spatial learning was not impaired, but passive avoidance performance was disrupted. Slow waves and high-voltage spindles were increased and beta activity decreased on the side of either quisqualate or ibotenate nucleus basalis lesioning. These results demonstrate that age-related neurophysiological and cognitive deficits result partially from the loss of cholinergic neurons in the nucleus basalis and that quisqualic acid nucleus basalis-lesioning in young rats may be used as a pharmacological model of the age-related cholinergic neuron loss.     

Mediation of passive avoidance learning by nicotinic hippocampo-entorhinal components in young rats

Young rats, 11, 16, and 20 days of age, received bilateral injections of three antinicotinic agents into the posteroventral hippocampo-subiculo-entorhinal area, and were trained to learn a cool-draft-stimulus, passive-avoidance task shortly after (17 min). Gallamine triethiodide had no action at low doses and provoked convulsions at higher concentrations. Pempidine tartrate produced age- and dose-dependent impairments of the passive avoidance, and was much more effective in younger groups (11 and 16 days) than at 20 days. alpha-bungarotoxin also induced dose-dependent deficits. These results, together with the mecamylamine-induced deficits already reported, suggest that nicotinic cholinergic synapses located in the posteroventral part of the hippocampal complex play a role in passive-avoidance learning in the young rat as soon as this type of conditioning is possible, but become relatively less important at older ages, when muscarinic mechanisms also become involved.     

Estrogen-induced changes in place and response learning in young adult female rats

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-microg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems.     

Compensation aids skilled reaching in aging and in recovery from forelimb motor cortex stroke in the rat

Compensatory movements mediate success in skilled reaching for food after stroke to the forelimb region of motor cortex (MtCx) in the rat. The present study asks whether the neural plasticity that enables compensation after motor stroke is preserved in aging. In order to avoid potential confounding effects of age-related negative-learning, rats were trained in a single pellet reaching task during young-adulthood. Subgroups were retested before and after contralateral forelimb MtCx stroke via pial stripping given at 3, 18, or 23 months of age. Over a two-month post-stroke rehabilitation period, end point measures were made of learned nonuse, recovery, retention, and performance ratings were made of reaching movement elements. Prior to stroke, young and aged rats maintained equivalent end point performance but older rats displayed compensatory changes in limb use as measured with ratings of the elements of forelimb movement. Following stroke, the aged groups of rats were more impaired on end point, movement, and anatomical measures. Nevertheless, the aged rats displayed substantial recovery via the use of compensatory movements. Thus, this study demonstrates that the neural plasticity that mediates compensatory movements after stroke in young adults is preserved prior to and following stroke in aging.     

The effects of eccentric exercise on motor performance in young and older women

Summary The purpose of the present study was to determine if old individuals show a greater exercise-induced decrement in motor performance and slower recovery compared to young individuals. Ten college-age women (23.6 years) and ten older women (67.4 years) performed an exercise consisting of 24 eccentric actions of the forearm flexors. In young subjects, eccentric exercise is known to produce repairable muscle damage. Before the exercise and for 5 days after, isometric strength, soreness, reaction time, and movement time were measured. For both groups, strength was reduced and soreness developed in the days following the exercise, generally indicating that muscle damage had occurred. The older subjects showed a slower strength recovery such that by 5 days after exercise they had not returned to their initial level of strength. There was no significant difference in soreness development between groups. Reaction time and movement time were not adversely affected by the exercise. Thus, the older subjects demonstrated a slower strength recovery after damage-inducing exercise, and, with regard to response speed, the older subjects could compensate for the impaired muscle function as well as the younger subjects.     

Effects of infant and adult amygdaloid lesions upon acquisition of two-way active avoidance by the adult rat: Influence of rearing conditions

When performed in the adult rat, bilateral and complete amygdalectomy resulted in a clear deficit in the acquisition of a 2-way active avoidance in a shuttle-box. When performed in the 7 day old rat pup, the same complete lesion resulted in no disruption of acquisition of the 2-way AA task by the rats when adult, irrespective of the environmental conditions in which they were reared from weaning. However, isolation-reared rats showed shorter response latencies than did group-reared rats. When the amygdaloid lesion was restricted to the centromedial area of the amygdala, operations carried out at 7 days resulted in a reliable impairment of the 2-way active avoidance in the initial phase of the acquisition, but only when the rats had been group-reared from weaning. The same lesion resulted in a reliable improvement in acquisition when the rats had been reared in isolation. In short, the degree of recovery of function with respect to 2-way AA acquisition following a bilateral amygdaloid lesion depends on the age at which the lesion is carried out (at infant or adult age), on the extent of the lesion (complete or restricted to the CM area) and on the rearing conditions (in groups or in isolation).     

Impaired acquisition of novel locomotor tasks in aged and norepinephrine-depleted F344 rats.

Performance of rats on a motor learning paradigm that has been demonstrated to be dependent upon cerebellar norepinephrine (NE) was studied in 20-month-old F344 rats. The behavioral task is identical to that described by Watson and McElligott: Rats are trained on a runway consisting of aluminum pegs arranged in a regular pattern. Rats receive a water reward at either end of the runway. Subsequent to training, rats are tested for running times on a runway with irregularly spaced rods. The ability of rats to improve their performance (decrease their running times) on this novel motor task is diminished in young rats that have received 6-hydroxydopamine lesions. Rats at 20 months of age are known to have deficits in cerebellar noradrenergic transmission; thus, the hypothesis to be tested was to determine if aged rats demonstrated performance deficits similar to young rats depleted of central stores of NE. The rate of acquisition of the task was determined by the decrease in running times with successive days of training. The ability of 20-month-old F344 rats to acquire proficiency on the novel motor task was impaired and the rate of acquisition of the novel motor task was not different from the young 6-hydroxydopamine-lesioned rats. In an attempt to distinguish between alterations in motor coordination and motor learning, additional tests of psychomotor performance were assessed for all groups of rats. These tests included a walking on 2.5- and 5-cm rods, speed of running on the motor task, and number and types of mistakes made on the motor learning task.(ABSTRACT TRUNCATED AT 250 WORDS)     

大鼠纹状体边缘区与海马逃避性学习记忆功能的比较

为了比较纹状体边缘区 (Mr D)与海马在逃避性学习记忆方面的差别 ,藉以探讨 Mr D与海马两个不同脑区在大脑学习记忆功能上的区别和作用地位。应用 Y迷宫训练大鼠后 2 4h,化学损毁大鼠双侧 Mr D或切断双侧穹窿海马伞 (fornix/fimbria,FF ) ,手术 5 d后再观察大鼠在 Y迷宫中学习记忆的行为表现。结果表明 ,化学损毁 Mr D组大鼠在 Y迷宫中的记忆能力和对照组相比 ,明显降低 ,差别显著 (P<0 .0 1) ;而切断双侧穹窿海马伞组大鼠与对照组相比 ,无显著性差异 (P>0 .0 5 )。说明大鼠在 Y迷宫中的逃避性学习记忆行为主要和 Mr D有关 ,和海马无明显关系。提示 Mr D和海马两个脑区在参与大脑的学习记忆功能方面 ,并非处于相同的位置     

Early learning failure impairs adult learning in rats

Early life experiences may affect adult learning ability. In two experiments we tested the effect of early learning failure on adult performance in Wistar rats. In the first experiment 17-day-old rats (PN17), but not 25-day-old rats (PN25), trained in a hidden platform water maze task showed deficits in tone-shock avoidance learning when they were 3-months-old. The second experiment, which included random-platform and non-platform control groups, confirmed the effect of early (PN18) spatial learning failure on adult avoidance learning. However, post-weaning training (PN25) without platform also tended to induce adult learning deficits as long as the adult task difficulty was increased. The older non-platform group did not differ from the impaired group which received early training in a fixed hidden platform task. The results are discussed in terms of the relevance of early learning outcome and developmental stage on adult general learning deficits which may be related to the learned helplessness phenomenon and developmental neural plasticity.     

Comparison of developmental trajectories for place and cued navigation in the Morris water task

Previous studies investigating the development of place and cued learning using the Morris water task are in disagreement regarding the day in development that each type of learning emerges. Here, place and cued navigation in the water task were examined in differently aged groups of young male and female rats (P17, P18, P19, P20, and P24) during a single day of training. When only distal cues were present, P20 and P24 but not younger rats learned the location of the hidden platform. In contrast, when a proximal cue marked the platform location, rats as young as P17 showed evidence of cue-controlled navigation, although only P18 and older rats exhibited cued learning. In line with most previous studies, these results indicate that cued learning emerges earlier in development than place learning and support a dissociation of developmental trajectories for the neural systems underlying the two types of navigation.     

Age and serial ablations of somatosensory cortex in the rat

The present study investigated the effects of one-stage and two-stage ablations of somatosensory cortex at 30 days, 270 days and 570 days of age on the acquisition of tactile discriminations in rats. Deficits in the ability to acquire tactile discriminations following such cortical lesions appeared to be similar regardless of the age at which the damage was sustained. Serial placement of the lesions did not attenuate the deficits in 30-day or 570-day-old rats. Some mitigation of the impairment was present in animals sustaining serial surgery at 270 days of age. In contrast, rats sustaining one-stage lesions at 570 days of age performed somewhat better than their age-mates sustaining two-stage lesions. Factors possibly relevant to the serial lesion effect and to recovery of function in general are suggested.     

Odor cue mediation of alcohol aversion learning in rats lacking gustatory neocortex.

Normal rats presented with a 5% alcohol solution followed by lithium chloride-induced illness quickly learned to avoid drinking alcohol. After training, the rats also avoided drinking water in the presence of the alcohol odor alone, whether tested immediately or 1 month later. In Experiment 1, rats with gustatory neocortex (GN) ablations also developed strong alcohol aversions when the alcohol solution was paired with illness. They also showed normal avoidance of drinking in the presence of the alcohol odor alone when tested soon after training. In Experiment 2, when normal rats were trained to avoid alcohol, given GN ablations, and then tested for retention 1 month later, avoidance of drinking water in the presence of the odor alone was significant but attenuated somewhat in relation to trained control rats. These data support the hypothesis that rats lacking GN partially acquire alcohol aversions by using odor cues and confirm that associative learning is intact in these rats despite the fact that GN rats display significant deficits in aversion learning when only tastes are paired with illness.     

Latent learning of spatial information is impaired in middle‐aged rats

The present study determined if the middle age related impairment that occurs with nonspatial latent learning also occurs in spatial latent learning. Thirty young (3‐months‐old) and 30 middle‐aged (12‐months‐old) male Sprague–Dawley rats were given either pre‐exposure to spatial cues surrounding a Barnes maze (SpatialPX), or pre‐exposure to just the maze (MazePX). They were then given 10 training trials in which they had to find a hidden escape box while experiencing an aversive environment produced by bright lights and wind. Results showed that young rats given the SpatialPX condition demonstrated faster escape latencies and fewer errors than young rats given the MazePX condition. However, middle‐aged rats given the SpatialPX condition did not show this improved performance. These findings indicate that the middle age learning deficit is not task specific, but rather is a general impairment in latent learning, possibly due to the early degeneration of the entorhinal cortex. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 309–315, 2013