Complete maternal deprivation affects social, but not spatial, learning in adult rats

The effects of maternal deprivation on learning of social and spatial tasks were investigated in female adult rats. Pups were reared artificially and received "lickinglike" tactile stimulation (AR animals) or were reared with their mothers (MR animals). In adulthood, subjects were tested on paradigms of spatial learning and on paradigms involving learning of social cues. Results showed that maternal deprivation did not affect performance on spatial learning, but it did impair performance on the three social learning tasks. The AR animals made no distinction between a new and a previously presented juvenile conspecific. AR animals also responded less rapidly than MR animals at test for maternal behavior 2 weeks after a postpartum experience with pups. Finally, AR animals did not develop a preference for a food previously eaten by a familiar conspecific whereas MR animals did. This study indicates that animals reared without mother and siblings show no deficits in spatial tasks while showing consistent deficits in learning involving social interactions.     

Nicotine enhances context learning but not context-shock associative learning

Nicotine has been found to enhance learning in a variety of tasks, including contextual fear conditioning. During contextual fear conditioning animals have to learn the context and associate the context with an unconditioned stimulus (footshock). As both of these types of learning co-occur during fear conditioning, it is not clear whether nicotine enhances one or both of these types of learning. To tease these two forms of learning apart, the authors made use of the context preexposure facilitation effect (CPFE). Acquisition of the CPFE requires that contextual and context-shock learning occurs on separate days, allowing for their individual manipulation. Nicotine (0.09 mg/kg) administered prior to contextual learning and retrieval enhanced the CPFE whereas administration prior to context-shock learning and retrieval had no effect. Thus, nicotine enhances contextual learning but not context-shock associative learning. Finally, the results are discussed in terms of a theory of how nicotine could alter hippocampal-cortical-amygdala interactions to facilitate contextual learning.     

Hippocampal granule cells are necessary for normal spatial learning but not for spatially-selective pyramidal cell discharge

Summary The effects of massive destruction of granule cells of the fascia dentata on the spatial and temporal firing characteristics of pyramidal cells in the CA1 and CA3 subfields of the hippocampus were examined in freely moving rats. Microinjections of the neurotoxin colchicine were made at a number of levels along the septo-temporal axis of the dentate gyri of both hemispheres, resulting in destruction of over 75% of the granule cells. By contrast there was relatively little damage to the pyramidal cell fields. As assessed by three different behavioral tests, the colchicine treatment resulted in severe spatial learning deficits. Single units were recorded from the CA1 and CA3 subfields using the stereotrode recording method while the animals performed a forced choice behavioral task on the radial 8-arm maze. Considering the extent of damage to the dentate gyrus, which has hitherto been considered to be the main source of afferent information to the CA fields, there was remarkably little effect on the spatial selectivity of place cell discharge on the maze, as compared to recordings from control animals. There was, however, a change in the temporal firing characteristics of these cells, which was manifested primarily as an increase in the likelihood of burst discharge. The main conclusion derived from these findings is that most of the spatial information exhibited by hippocampal pyramidal cells is likely to be transmitted from the cortex by routes other than the traditional trisynaptic circuit. These routes may include the direct projections from entorhinal layers II and III to CA3 and CA1, respectively.     

Sleep after learning aids the consolidation of factual knowledge,but not relearning

Study ObjectivesSleep strengthens and reorganizes declarative memories, but the extent to which these processes benefit subsequent relearning of the same material remains unknown. It is also unclear whether sleep-memory effects translate to educationally realistic learning tasks and improve long-term learning outcomes.MethodsYoung adults learned factual knowledge in two learning sessions that were 12 h apart and separated by either nocturnal sleep (n = 26) or daytime wakefulness (n = 26). Memory before and after the retention interval was compared to assess the effect of sleep on consolidation, while memory before and after the second learning session was compared to assess relearning. A final test 1 week later assessed whether there was any long-term advantage to sleeping between two study sessions.ResultsSleep significantly enhanced consolidation of factual knowledge (p = 0.01, d = 0.72), but groups did not differ in their capacity to relearn the materials (p = 0.72, d = 0.10). After 1 week, a numerical memory advantage remained for the sleep group but was no longer significant (p = 0.21, d = 0.35).ConclusionsReduced forgetting after sleep is a robust finding that extends to our ecologically valid learning task, but we found no evidence that sleep enhances relearning. Our findings can exclude a large effect of sleep on long-term memory after 1 week, but hint at a smaller effect, leaving open the possibility of practical benefits from organizing study sessions around nocturnal sleep. These findings highlight the importance of revisiting key sleep-memory effects to assess their relevance to long-term learning outcomes with naturalistic learning materials.     

The perirhinal cortex of the rat is necessary for spatial memory retention long after but not soon after learning

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.     

Age affects chunk-based, but not rule-based learning in artificial grammar acquisition

Explicit learning is well known to decline with age, but divergent results have been reported for implicit learning. Here, we assessed the effect of aging on implicit vs. explicit learning within the same task. Fifty-five young (mean 32 years) and 55 elderly (mean 64 years) individuals were exposed to letter strings generated by an artificial grammar. Subsequently, participants classified novel strings as grammatical or nongrammatical. Acquisition of superficial ("chunk-based") and structural ("rule-based") features of the grammar were analyzed separately. We found that overall classification accuracy was diminished in the elderly, driven by decreased performance on items that required chunk-based knowledge. Performance on items requiring rule-based knowledge was comparable between groups. Results indicate that rule-based and chunk-based learning are differentially affected by age: while rule-based learning, reflecting implicit learning, is preserved, chunk-based learning, which contains at least some explicit learning aspects, declines with age. Our findings may explain divergent results on implicit learning tasks in previous studies on aging. They may also help to better understand compensatory mechanisms during the aging process.     

Taste avoidance, but not aversion, learning in rats lacking gustatory cortex.

Control rats rapidly learned to avoid drinking either a sucrose solution (Experiment 1) or a NaCl solution (Experiment 2) when the taste was paired with illness. These rats also produced aversive reactivity to each of these solutions in a taste reactivity test. Rats that lacked gustatory cortex (GC) learned to avoid drinking sucrose and NaCl, albeit at a slower rate than control rats. GC rats failed to display aversive reactivity to these tastes. The GC rats did show normal aversive reactivity to a strong quinine HCl solution during additional tests. It is suggested that the avoidance developed by GC rats did not entail a palatability shift of the conditional stimulus as it did in control rats. This altered learning strategy may account for the consistent learning deficits found in GC rats trained to avoid tastes.     

Area postrema lesions impair flavor-toxin aversion learning but not flavor-nutrient preference learning

Rats with lesions of the area postrema (APX) or sham lesions were trained to associate flavored solutions with positive or negative postingestive consequences. The APX rats were similar to controls in learning preferences for flavors paired with concurrent intragastric infusions of maltodextrin or corn oil and for a flavor paired with delayed maltodextrin infusions. In contrast, the APX rats displayed impaired aversion learning for flavors paired with toxic drug treatments (lithium chloride infusion or methylscopolamine injection). The aversion learning deficit ranged from mild to total, depending on training procedures. These findings confirm the important role of the area postrema in flavor-toxin learning but provide no evidence for its involvement in flavor-nutrient conditioning.     

The synthetic cannabinoid WIN 55212-2 differentially modulates thigmotaxis but not spatial learning in adolescent and adult animals

Unlike Δ(9)-THC, the synthetic compound WIN 55212-2 (WIN) is a full agonist of endogenous cannabinoid receptors. Previous work has shown Δ(9)-THC to affect adolescent and adult animals differently on numerous behavioral measures of spatial memory, anxiety, and locomotor activity. However, far less is known about the developmental and neurobehavioral effects of WIN. To address this, we assessed the effect of WIN (1mg/kg) on spatial learning in adolescent and adult rats using the Morris water maze. While all animals demonstrated decreased swim distance across days, WIN affected adolescents and adults differently. It improved performance in adolescents and resulted in a nearly significant performance decrement in adults. However, these effects were significantly related to thigmotaxis, which declined across days in the water maze testing protocol. WIN reduced thigmotaxis on days 1 and 2 (but not days 3-5) only in adolescents. The effect of age, treatment, and the age×treatment interaction was eliminated after controlling for thigmotaxis. These results indicate that WIN affects thigmotaxis rather than spatial reference memory. More importantly, these findings indicate a dissociation between the developmental effects of THC and the synthetic CB1 receptor agonist, WIN 55212-2. We suggest that the role of thigmotaxis be carefully evaluated in future neurodevelopmental studies of spatial learning, especially those investigating the endocannabinoid system.     

Sleep modulates word-pair learning but not motor sequence learning in healthy older adults

Sleep benefits memory across a range of tasks for young adults. However, remarkably little is known of the role of sleep on memory for healthy older adults. We used 2 tasks, 1 assaying motor skill learning and the other assaying nonmotor/declarative learning, to examine off-line changes in performance in young (20-34 years), middle-aged (35-50 years), and older (51-70 years) adults without disordered sleep. During an initial session, conducted either in the morning or evening, participants learned a motor sequence and a list of word pairs. Memory tests were given twice, 12 and 24 hours after training, allowing us to analyze off-line consolidation after a break that included sleep or normal wake. Sleep-dependent performance changes were reduced in older adults on the motor sequence learning task. In contrast, sleep-dependent performance changes were similar for all 3 age groups on the word pair learning task. Age-related changes in sleep or networks activated during encoding or during sleep may contribute to age-related declines in motor sequence consolidation. Interestingly, these changes do not affect declarative memory.     

Amygdala kindling increased fear-response, but did not impair spatial memory in rats.

The behavioral effects of amygdala kindling, a model of experimental epilepsy in rats, are reported. The animals were stimulated twice a day until stage 5 (generalized clonic) seizures were obtained three times. Two weeks later the performance of the amygdala-kindled and sham-operated rats was tested in the open-field test, on the elevated plus maze, elevated bridges, and in the Morris water maze. The results show that amygdala kindling decreased exploratory and other motor activity in the open-field test, had anxiogenic effects on the elevated plus-maze, decreased boldness on the elevated bridges, but had a negligible affect in the spatial memory task. These results suggest that amygdala kindling affects the normal fear reaction of rats, a response that is known to be mediated through the amygdaloid pathways.     

Reduced palatability in lithium- and activity-based, but not in amphetamine-based, taste aversion learning

Conditioned taste aversions (CTA) based on lithium chloride (Experiment 1), amphetamine (Experiment 2), and wheel running (Experiment 3) were examined using the analysis of the microstructure of licking to measure the palatability of the taste serving as the conditioned stimulus (CS). Pairing saccharin with amphetamine reduced saccharin intake without reducing the size of licking clusters, initial lick rate, or the distribution of inter-lick intervals (ILIs) within a cluster. By contrast, pairing saccharin with lithium or wheel-running reduced saccharin intake as well as lick cluster size, initial lick rate, and the distribution of ILIs within a cluster. As lick cluster size, initial lick rate, and ILI distribution can be used as indices of stimulus palatability, the current results indicate that taste aversions based on either lithium or activity reduced the palatability of the CS. This suggests that aversions based on both lithium and wheel running involve conditioned nausea to the CS taste. The absence of similar changes in licking microstructure with amphetamine-based CTA is consistent with other evidence indicating this does not involve nausea.     

Impairment of movement initiation and execution but not preparation in idiopathic dystonia

Imaging studies have reported impaired activation of the striatum and their frontal projection sites in dsytonia, areas which are considered to play a role in motor preparation, movement initiation and execution. The aim of this study was to investigate the processes of motor preparation, response initiation and execution in patients with idiopathic torsion dystonia (ITD). We assessed 12 patients with ITD and 12 age-matched controls on a number of reaction time (RT) tasks that differed in degree of motor preparation possible. Subjects performed a visual simple RT (SRT) task, an uncued four-choice reaction time (CRT) task and a fully precued four-choice RT task. A stimulus 1-stimulus 2 (S1-S2) paradigm was used. The warning signal/precue (S1) preceded the imperative stimulus (S2) by either 0 ms (no warning signal or precue) 200 ms, 800 ms, 1,600 ms or 3,200 ms. The patients with ITD had significantly slower RTs and movement times than normals across all RT tasks. The unwarned SRT trials were significantly faster than the uncued CRT trials for both groups. For both groups, precued CRTs were significantly faster than the uncued CRTs. The results show that while response initiation and execution are significantly slower in patients with ITD than normals, movement preparation is not quantitatively or qualitatively different. The results are discussed in relation to previous imaging, behavioural and electrophysiological studies and models of fronto-striatal dysfunction in ITD.     

Neural correlates of perceptual learning in a sensory-motor, but not a sensory, cortical area

This study aimed to identify neural mechanisms that underlie perceptual learning in a visual-discrimination task. We trained two monkeys (Macaca mulatta) to determine the direction of visual motion while we recorded from their middle temporal area (MT), which in trained monkeys represents motion information that is used to solve the task, and lateral intraparietal area (LIP), which represents the transformation of motion information into a saccadic choice. During training, improved behavioral sensitivity to weak motion signals was accompanied by changes in motion-driven responses of neurons in LIP, but not in MT. The time course and magnitude of the changes in LIP correlated with the changes in behavioral sensitivity throughout training. Thus, for this task, perceptual learning does not appear to involve improvements in how sensory information is represented in the brain, but rather how the sensory representation is interpreted to form the decision that guides behavior.     

Hippocampal mossy fibers and radial-maze learning in the mouse: a correlation with spatial working memory but not with non-spatial reference memory

One hundred and eight male mice from nine different inbred strains were tested for two aspects of learning in an eight-arm radial maze. In the first experimental arrangement of the maze, measuring spatial working memory, clear strain differences were found on the fifth day of training. Furthermore, this type of learning showed a high positive correlation with the size of the intra- and infrapyramidal hippocampal mossy fiber terminal field as revealed with Timm's staining. In the second experiment, in which non-spatial reference memory was tested, significant strain differences were found for the learning variables, but there were no significant covariations with the sizes of the intra- and infrapyramidal mossy fiber terminal fields. These results, combined with previous data, suggest that heritable variations of the hippocampal intra- and infrapyramidal mossy fiber projection influence processes determining spatial learning capabilities in mice.     

Estradiol,but not raloxifene,improves aspects of spatial working memory in aged ovariectomized rhesus monkeys

Estrogen replacement therapy (ERT) alleviates many postmenopausal symptoms but whether it also benefits cognitive function remains controversial. Further, since estrogen increases the risk of breast and uterine cancers, a new class of compounds, called selective estrogen receptor modulators (SERMs) is being considered as possible alternative to ERT. The SERM raloxifene is particularly interesting because, like estrogen, it improves lipid metabolism and reduces bone loss, without adverse effects on the breast or uterus. Little is known, however, about its effect upon cognitive function.We used a rhesus monkey model of human menopause to examine the effects of ERT and raloxifene on cognitive function. We tested 5 aged females (21-24 years old) ovariectomized long-term (10-16 years) on a battery of age-sensitive tasks, including the Delayed Response (DR), the Delayed Non-Matching-to-Sample-10 min (DNMS-10 min) and the spatial-Delayed Recognition Span Test (DRST). Monkeys were tested 5 days a week on each task for 9 consecutive months, while undergoing treatments with placebo, ethinyl estradiol (EE(2)), and raloxifene in alternating 28-days blocks. EE(2) transiently enhanced the working memory component of the spatial-DRST, but did not affect performance on the other tasks of the battery. Raloxifene had no effect on cognitive performance. These findings indicate that estradiol is able to enhance some aspects of spatial working memory in aged monkeys despite many years of estrogenic deprivation. Further, they suggest that raloxifene does not affect cognitive function after long-term ovarian hormone deprivation.     

Inhibition of adult hippocampal neurogenesis disrupts contextual learning but spares spatial working memory,long-term conditional rule retention and spatial reversal

Neurogenesis in the adult dentate gyrus (DG) of the hippocampus has been implicated in neural plasticity and cognition but the specific functions contributed by adult-born neurons remain controversial. Here, we have explored the relationship between adult hippocampal neurogenesis and memory function using tasks which specifically require the participation of the DG. In two separate experiments several groups of rats were exposed to fractionated ionizing radiation (two sessions of 7 Gy each on consecutive days) applied either to the whole brain or focally, aiming at a region overlying the hippocampus. The immunocytochemical assays showed that the radiation significantly reduced the expression of doublecortin (DCX), a marker for immature neurons, in the dorsal DG. Ultrastructural examination of the DG region revealed disruption of progenitor cell niches several weeks after the radiation. In the first experiment, whole-brain and focal irradiation reduced DCX expression by 68% and 43%, respectively. Whole-brain and focally-irradiated rats were unimpaired compared with control rats in a matching-to-place (MTP) working memory task performed in the T-maze and in the long-term retention of the no-alternation rule. In the second experiment, focal irradiation reduced DCX expression by 36% but did not impair performance on (1) a standard non-matching-to-place (NMTP) task, (2) a more demanding NMTP task with increasingly longer within-trial delays, (3) a long-term retention test of the alternation rule and (4) a spatial reversal task. However, rats irradiated focally showed clear deficits in a “purely” contextual fear-conditioning task at short and long retention intervals. These data demonstrate that reduced adult hippocampal neurogenesis produces marked deficits in the rapid acquisition of emotionally relevant contextual information but spares spatial working memory function, the long-term retention of acquired spatial rules and the ability to flexibly modify learned spatial strategies.     

Inactivation of dorsolateral striatum impairs acquisition of response learning in cue-deficient, but not cue-available, conditions

Rats received bilateral injections of lidocaine or artificial cerebrospinal fluid (aCSF) into the doisolateral striatum 6 min prior to training in either a plus- or T-shaped maze under cue-poor or cue-available conditions. Lidocaine injections significantly impaired acquisition in the cue-poor environments, but not in the cue-available environments. In addition, aCSF control rats trained in a plus-maze in a cue-poor environment reached criterion much more rapidly than did rats trained in a cue-available environment. These findings suggest that cue availability can permit acquisition of response learning in a manner that is not dependent on activity of the striatum. However, in a cue-poor environment, alternate strategies may be less readily available, revealing more efficient striatal involvement in response learning.     

Amygdala central nucleus function is necessary for learning, but not expression, of conditioned auditory orienting

In Pavlovian appetitive conditioning, rats often acquire 2 classes of conditioned responses: those whose form is determined by the reinforcer, and those whose form is determined by characteristics of the conditioned stimulus (CS). Consistent with the results of previous lesion studies, reversible inactivation of amygdala central nucleus function during pairings of an auditory CS with food prevented the acquisition of conditioned orienting responses specific to auditory CSs, whereas food-related conditioned behaviors were acquired normally. Neither inactivation nor posttraining neurotoxic lesions of the central nucleus affected the expression of previously acquired conditioned orienting. Thus, although the central nucleus is critical to the acquisition of information required for conditioned orienting to auditory cues, it is not needed for maintaining this information for later use.