Spatial learning in the T-maze; the influence of direction, turn, and food location.
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Cholesterol treatment facilitates spatial learning performance in DBA/2Ibg mice.
DBA/2Ibg mice were treated with cholesterol pellets for 11 days. On the seventh day after treatment, animals began 5 consecutive days of training on the spatial form of Morris water task, followed on the third and fourth days by a probe trial, and random platform training on the fifth day. DBA mice with cholesterol pellets exhibited enhanced performance compared to DBA mice that underwent a sham surgery. Our results suggest that subchronic treatment with the steroid hormone precursor, cholesterol, enhances spatial learning performance in DBA mice.
Animals↗
Endomorphin-2 but not Leu-enkephalin modulates spatial learning when microinjected in the CA3 region of the rat hippocampus.
The recently discovered endogenous mu-selective opioid peptide, endomorphin-2, and the endogenous delta-selective opioid peptide, Leu-enkephalin, were tested for their ability to affect spatial learning in the Morris water task. It was found that microinjection of 10 nmol endomorphin-2 into the CA3 region of the rat hippocampus significantly impaired spatial learning. However, the two lower doses tested, 3.3 and 1 nmol, had no effect in this test. Leu-enkephalin did not have any effect on spatial learning at the two doses tested (10 and 3.3 nmol). Neither peptide had any effect on motor performance as measured by swim speed. The results indicate that mu-receptors in the CA3 region of the rat hippocampus are more relevant than delta-receptors for spatial learning.
Animals↗
Learning-induced reversal of the effect of noradrenalin on the postburst AHP.
Pyramidal neurons in the piriform cortex from olfactory-discrimination-trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, I(AHP) and sI(AHP), that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks I(A)(HP), reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance I(AHP) while suppressing (S)I(AHP), reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the I(AHP) current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, sI(AHP). Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.
Animals↗
Effects of the serotonin receptor agonists 8-OH-DPAT and TFMPP on learning as assessed using a novel water maze.
We evaluated the effects of two drugs active at serotonin receptors, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, a 5-HT1A agonist) and N-3-trifluoromethylphenyl)piperazine hydrochloride (TFMPP, a 5-HT2C agonist) on learning using a novel water maze previously characterized in our laboratory. The water maze utilized is a traditional type of maze with alleyways and doors through which the rats learn to swim to reach a platform, unlike the open pool Morris water maze task. Performance is assessed by swim time required to reach the platform and errors committed. Following initial training on maze configuration A, rats were assigned to saline, TFMPP and 8-OH-DPAT treatment groups and tested for performance once per dose, 30 min after administration of drug (0.25, 0.5, and 1.0 mg/kg IP). Swim times were significantly increased as compared to saline for all doses for both drugs. The error rate was increased for 8-OH-DPAT at all doses, while TFMPP had no effect on error rate at any dose. Next, rats were challenged to learn new mazes following daily administration of 0.25 or 0.5 mg/kg of each drug 30 min prior to each daily swim trial. Rats given 0.25 mg/kg of 8-OH-DPAT learned new maze C more slowly than saline-treated rats, while TFMPP had no effect at this dose. At the higher dose of 0.5 mg/kg, tested on new maze B, TFMPP administration significantly increased swim times but not errors, while this dose of 8-OH-DPAT markedly increased both swim time and errors. Finally, rats from all groups were tested on maze E after drug administration was discontinued, and there were no performance differences among groups. These data suggest that serotonin1A receptors may inhibit learning.
8-Hydroxy-2-(di-n-propylamino)tetralin↗
Loss of cholinergic phenotype in basal forebrain coincides with cognitive decline in a mouse model of Down's syndrome.
Mice with segmental trisomy of chromosome 16 (Ts65Dn) have been used as a model for Down's syndrome. These mice are born with a normal density of basal forebrain cholinergic neurons but, like patients with Down's syndrome, undergo a significant deterioration of these neurons later in life. The time course for this degeneration of cholinergic neurons has not been studied, nor is it known if it correlates with the progressive memory and learning deficits described. Ts65Dn mice that were 4, 6, 8, and 10 months old were sacrificed for evaluation of basal forebrain morphology. Separate groups of mice were tested on visual or spatial discrimination learning and reversal. We found no alterations in cholinergic markers in 4-month-old Ts65Dn mice, but thereafter a progressive decline in density of cholinergic neurons, as well as significant shrinkage of cell body size, was seen. A parallel loss of staining for the high-affinity nerve growth factor receptor, trkA, was observed at all time points, suggesting a biological mechanism for the cell loss involving this growth factor. Other than transient difficulty in learning the task requirements, there was no impairment of trisomic mice on visual discrimination learning and reversal, whereas spatial learning and reversal showed significant deficits, particularly in the mice over 6 months of age. Thus, the loss of ChAT-immunoreactive neurons in the basal forebrain was coupled with simultaneous deficits in behavioral flexibility on a spatial task occurring for the first time around 6 months of age. These findings suggest that the loss of cholinergic function and the simultaneous decrease in trkA immunoreactivity in basal forebrain may directly correlate with cognitive impairment in the Ts65Dn mouse
Animals↗
Behavioral effects of neonatal cocaine exposure using a rodent model.
This study examined the effects of neonatal cocaine exposure on behavior using a rodent model. Rat pups were implanted with intragastric cannulas on postnatal day (PND) 4 and artificially reared (AR) from PND 4-10. The AR groups included two cocaine doses (20 mg/kg per day and 60 mg/kg per day) and an AR control. A sham surgery control group was also included that was reared naturally by its dam. Offspring from these neonatal treatment groups were examined for suckling performance (PND 13), passive avoidance learning (PND 23-24), activity (PND 18-21), or spontaneous alternation (PND 21). Neonatal cocaine exposure had no effect on suckling measures or passive avoidance learning. Activity was increased in the 60 mg/kg per day cocaine group relative to controls. In addition, spontaneous alternation was delayed in the 20 mg/kg per day cocaine-exposed females relative to all other groups. These data suggest that neonatal cocaine exposure may alter performance on some relatively simple tasks. More work is clearly warranted to look at the effects of neonatal cocaine exposure on more complex behaviors.
Animals↗
Intraseptal tacrine-induced disruptions of spatial memory performance.
The medial septal nucleus regulates the physiology and emergent functions (e.g., memory formation) of the hippocampal formation. This nucleus is particularly rich in cholinergic receptors and is a putative target for the development of cholinomimetic cognitive enhancing drugs. Several studies have examined the direct effects of intraseptal cholinomimetic treatments and the results have been somewhat conflicting with both promnestic and amnestic effects. Several variables (e.g., age, task difficulty, timing of drug administration) may influence treatment outcome. The present study examined the effects of intraseptal infusion of the acetylcholinesterase inhibitor tacrine (0-25 microg/0.5 microl) on spatial memory performance. Tacrine was infused into the medial septum just prior to testing. Tacrine infusions did not significantly affect the number of correct choices in the first eight entries, or the number of correct choices until an error. This treatment did not alter the angle of arm entries, or impair the animals' ability to complete the task (enter all baited arms). However, tacrine produced a linear dose-dependent increase in errors, doubling (12.5 microg) and tripling (25.0 microg) the number of errors made before rats completed the task. The deficit demonstrates that activation of intraseptal cholinergic receptors can disrupt spatial memory performance. These findings are discussed with regards to septohippocampal-dependent memory processes and the development of therapeutic strategies in the treatment of age-related memory disorders.
Analysis of Variance↗
Effects of permethrin given before mating on the behavior of F1-generation in mice.
Permethrin, a type I synthetic pyrethroid insecticide, was evaluated through assessment of the behavioral development of F1 progeny of mice. Groups each of 30 male and 30 female ICR (CD-1) mice, as F0-generation, were given 0, 4.9, 9.8, and 19.6 mg/kg/d permethrin by gavage for 4 weeks before mating. Behavioral endpoints of motor reflexes, motor coordination, and activity were evaluated in F1 progeny. Clinical signs of toxicity including salivation, hyperactivity, and liquid feces which attributed to permethrin were observed in the F0-mice treated with 9.8 and 19.6 mg/kg/d. Reduction of body weight became evident only during gestation and lactation periods for the middle and high dose groups. Significant differences in the development of reflexes, swimming ability, and open field activity were evident in the offspring for the 9.8 and 19.6 mg/kg/d dose groups compared to the control group. These results show that permethrin at dose levels of 9.8 and 19.6 mg/kg/d can induce a significant risk to the offspring following treatment of F0-mice before mating. The NOEL obtained in this study for the effects of permethrin on the development of the F1-progeny is 4.9 mg/kg/d.
Analysis of Variance↗
Acquisition of an appetitive behavior reverses the effects of long-term treatment with lithium in rats.
Rats exposed to a long-term treatment with lithium chloride develop a deficit of avoidance accompanied by a reduction in the basal levels of extraneuronal dopamine and in dopamine accumulation in the nucleus accumbens shell after acute uptake inhibition. Such a condition is similar to that of an experimental model of depression induced by exposing rats to a chronic stress procedure. Rats exposed to chronic stress are also unable to acquire an appetitive behavior sustained by a highly palatable food. Thus, it was studied whether rats fed a diet containing lithium would develop an appetitive behavior induced by a pure hedonic stimulus. Rats on the lithium diet developed a clear-cut escape deficit condition accompanied by a decreased dopamine output in the nucleus accumbens shell; nevertheless, they learned the appetitive behavior within a similar period to controls. The development of the appetitive behavior coincided with the recovery of the capacity to avoid a noxious stimulus and with the return of the dopaminergic transmission in the nucleus accumbens shell to values similar to those of control rats. It may be concluded that the mechanism of action underlying the behavioral and neurochemical sequelae of a chronic stress is distinct from that of the analogous effects produced by lithium.
Animals↗
The opposite effects of cysteamine on the acquisition of two different tasks in mice are associated with bidirectional testing-induced changes in hippocampal adenylyl cyclase activity.
The hypothesis of a role for hippocampal somatostatin (SS-14) in learning and memory processes was further examined by means of 2 selective learning tasks that were previously shown to be either impaired (spatial discrimination task) or facilitated (barpressing task) by hippocampal lesions. Results showed that subcutaneous injections of cysteamine (160 mg/kg) (a) impaired acquisition of the spatial task while producing an opposite (i.e., facilitative) effect on acquisition of the barpressing task and (b) produced an up regulation of hippocampal adenylyl cyclase (AC) activity, which was antagonized by spatial discrimination training but enhanced by training in the barpressing task. Moreover, opposite task-dependent training-induced changes in hippocampal AC activity was observed in saline-treated mice. These results suggest that bidirectional regulatory mechanisms of hippocampal function involving both SS-14 and ACs may occur as a function of the type of learning.
Adenylyl Cyclases↗
Hippocampal function and spatial memory: evidence from functional neuroimaging in healthy participants and performance of patients with medial temporal lobe resections.
Several strategies can be used to find a destination in the environment. Using a virtual environment, the authors identified 2 strategies dependent on 2 different memory systems. A spatial strategy involved the use of multiple landmarks available in the environment, and a response strategy involved right and left turns from a given start position. Although a probe trial provided an objective measure of the strategy used, classification that was based on verbal reports was used in small groups to avoid risks of misclassification. The authors first demonstrated that the spatial strategy led to a significant activity of the hippocampus, whereas the response strategy led to a sustained activity in the caudate nucleus. Then, the authors administered the task to 15 patients with lesions to the medial temporal lobe, showing an impaired ability using the spatial strategy. Imaging and neuropsychological results are discussed to shed light on the human navigation system.
Adult↗
Brevican-deficient mice display impaired hippocampal CA1 long-term potentiation but show no obvious deficits in learning and memory.
Brevican is a brain-specific proteoglycan which is found in specialized extracellular matrix structures called perineuronal nets. Brevican increases the invasiveness of glioma cells in vivo and has been suggested to play a role in central nervous system fiber tract development. To study the role of brevican in the development and function of the brain, we generated mice lacking a functional brevican gene. These mice are viable and fertile and have a normal life span. Brain anatomy was normal, although alterations in the expression of neurocan were detected. Perineuronal nets formed but appeared to be less prominent in mutant than in wild-type mice. Brevican-deficient mice showed significant deficits in the maintenance of hippocampal long-term potentiation (LTP). However, no obvious impairment of excitatory and inhibitory synaptic transmission was found, suggesting a complex cause for the LTP defect. Detailed behavioral analysis revealed no statistically significant deficits in learning and memory. These data indicate that brevican is not crucial for brain development but has restricted structural and functional roles.
Animals↗
Effects of entorhinal cortex lesions on memory in different tasks.
Lesions of the entorhinal cortex produce retrograde memory impairment in both animals and humans. Here we report the effects of bilateral entorhinal cortex lesions caused by the stereotaxic infusion of N-methyl-D-aspartate (NMDA) in rats at two different moments, before or after the training session, on memory of different tasks: two-way shuttle avoidance, inhibitory avoidance and habituation to an open field. Pre- or post-training entorhinal cortex lesions caused an impairment of performance in the shuttle avoidance task, which agrees with the previously described role of this area in the processing of memories acquired in successive sessions. In the inhibitory avoidance task, only the post-training lesions had an effect (amnesia). No effect was observed on the open field task. The findings suggest that the role of the entorhinal cortex in memory processing is task-dependent, perhaps related to the complexity of each task.
Alzheimer Disease↗
[Effect of immunization to cholecystokinin fragment (30-33) on the behavior of albino rats].
Active immunisation of albino rats by the BSA-conjugated CCK-4 induced formation of antibodies to the CCK-4 and some long-term changes of the rat behaviour. These changes were contrary to anxiogenic effect of the CCK-4 and demonstrated an anxiolytic effect of the immunisation. The data obtained suggest a possibility of an immunocorrection of pathological anxiety and fear by an inverse immunoregulation.
Alcohol Drinking↗
Long term administration of Hypericum perforatum improves spatial learning and memory in the water maze.
The aim of the present study is to investigate the effects of long-term Hypericum perforatum treatment on spatial learning and memory in rats. Hypericum preparation (HP) standardized to 0.3% hypericin content was administered orally for 9 weeks in doses of 4.3 and 13 microg/kg corresponding to therapeutic dosages in humans of 0.3 and 0.9 mg of total hypericins daily. A Morris water maze paradigm was used. The mean escape latency over 4 d for the Control group (21.9 s) and HP 4.3 group (21.7 s) was significantly greater than the latency of the HP 13 group (15.8s). In the probe trial on day 5, the HP 13 group crossed the correct annulus in the SE quadrant more often (4.5) than the other groups: Con (2.4) and HP 4.3 (3.1). After completion of the behavioral experiment, the regional brain concentrations of monoamines and metabolites were estimated in selected brain regions, i.e. prefrontal cortex, hippocampus and hypothalamus. Analysis of variance (ANOVA) demonstrated significant differences in the content of monoamines and metabolites between the treatment groups compared to the Control. The increased 5-hydroxytryptamine (5-HT) levels in the prefrontal cortex correlated positively with the retention of spatial memory. These findings show that the long-term administration of Hypericum perforatum can improve learning and spatial memory with significant changes in the content of monoamines in several brain regions.
Animals↗
Facilitation of learning after lesions of the tuberomammillary nucleus region in adult and aged rats.
The tuberomammillary nucleus (TM) located in the posterior part of the hypothalamus is the main source of neuronal histamine in the central nervous system. Recent work from our laboratories has indicated an involvement of the TM region in neuronal plasticity and reinforcement processes. In the present study, we investigated the effects of TM lesions on the performance of adult and aged Wistar rats in a set of learning tasks, which differed in terms of complexity and reward contingencies (habituation learning, inhibitory avoidance, discrimination learning, Morris water maze). An improvement was found in every test applied, indicating that TM lesions seem to generally enhance learning and memory capacities independent of the special demands of a given task. Age-related learning deficits were strongly diminished. Immunohistochemistry revealed that the excitotoxic lesions used to destroy the TM region led to a marked decrease in the number of histamine-positive neurons in the vicinity of the injection site, indicating an involvement of the brain histaminergic system in the observed behavioral changes.
Aging↗
Multiple points of entry into a circular enclosure prevent place learning despite normal vestibular orientation and cue arrays: evidence for map resetting.
This study identified sources of map orientation critical for successful spatial problem solving by rats of a plus maze embedded in water. Disorientation slowed, but it did not prevent acquisition of goal location. Use of a circular enclosure with multiple points of entry prevented reliable goal location. A single entry point enabled the rats to locate a fixed goal. A cue array within the enclosure was ineffective in providing orientation. These data suggest that stable map orientation can be derived from entry location when enclosure geometry is uniformative, but is not readily taken from cue arrays. They further suggest that map orientation is reset when rats enter an enclosure.
Animals↗