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Water maze learning and hippocampal synaptic plasticity in streptozotocin-diabetic rats: effects of insulin treatment.

Streptozotocin-diabetic rats express deficits in water maze learning and hippocampal synaptic plasticity. The present study examined whether these deficits could be prevented and/or reversed with insulin treatment. In addition, the water maze learning deficit in diabetic rats was further characterized. Insulin treatment was commenced at the onset of diabetes in a prevention experiment, and 10 weeks after diabetes induction in a reversal experiment. After 10 weeks of treatment, insulin-treated diabetic rats, untreated diabetic rats and non-diabetic controls were tested in a spatial version of the Morris water maze. Next, hippocampal long-term potentiation (LTP) was measured in vitro. To further characterize the effects of diabetes on water maze learning, a separate group of rats was pre-trained in a non-spatial version of the maze, prior to exposure to the spatial version. Both water maze learning and hippocampal LTP were impaired in diabetic rats. Insulin treatment commenced at the onset of diabetes prevented these impairments. In the reversal experiment, insulin treatment failed to reverse established deficits in maze learning and restored LTP only partially. Non-spatial pre-training abolished the performance deficit of diabetic rats in the spatial version of the maze. It is concluded that insulin treatment may prevent but not reverse deficits in water maze learning and LTP in streptozotocin-diabetic rats. The pre-training experiment suggests that the performance deficit of diabetic rats in the spatial version of the water maze is related to difficulties in learning the procedures of the maze rather than to impairments of spatial learning.

Animals↗

Distinct patterns of brain oscillations underlie two basic parameters of human maze learning.

We examine how oscillations in the intracranial electroencephalogram (iEEG) relate to human maze learning. Theta- band activity (4-12 Hz in rodents; 4-8 Hz in humans) plays a significant role in memory function in rodents and in humans. Recording intracranially in humans, we have reported task-related, theta-band rhythmic activity in the raw trace during virtual maze learning and during a nonspatial working memory task. Here we analyze oscillations during virtual maze learning across a much broader range of frequencies and analyze their relationship to two task variables relevant to learning. We describe a new algorithm for detecting oscillatory episodes that takes advantage of the high signal-to-noise ratio and high temporal resolution of the iEEG. Accounting for the background power spectrum of the iEEG, the algorithm allows us to directly compare levels of oscillatory activity across frequencies within the 2- to 45-Hz band. We report that while episodes of oscillatory activity are found at various frequencies, most of the rhythmic activity during virtual maze learning occurs within the theta band. Theta oscillations are more prevalent when the task is made more difficult (manipulation of maze length). However, these oscillations do not tend to covary significantly with decision time, a good index of encoding and retrieval operations. In contrast, lower- and higher-frequency oscillations do covary with this variable. These results suggest that while human cortically recorded theta might play a role in encoding, the overall levels of theta oscillations tell us little about the immediate demands on encoding or retrieval. Finally, different patterns of oscillations may reflect distinct underlying aspects of memory function.

Adolescent↗

Genetic and environmental correlations between brain weight and maze learning in inbred strains of mice and their F1 hybrids.

The relationships among body weight, cerebellum weight, cerebrum weight, maze-learning ability in a double T-maze, and discrimination learning in a Y-maze were studied in six inbred strains of mice and some of their F1 hybrids. The subjects were 131 male albino mice from 14 genotypic groups: five inbred groups and nine groups of crossbred offspring. Intra- and intergroup correlations were computed between all possible pairs of the anatomical and behavioral traits. A significant difference between the intragroup and intergroup correlations for any pair of variables was taken to indicate the presence of a genetic correlation between the two variables. On this basis, positive genetic correlations were indicated between T-maze learning ability and Y-maze learning ability, between body weight and T-maze learning ability, and possibility between body weight and both cerebellum and cerebrum weight and between cerebrum weight and T-maze learning ability. Negative genetic correlations were indicated between cerebellum weight and running time in both mazes and between total number of successes in the Y-maze and Y-maze running time.

Animals↗

Asymmetries in intermanual transfer of maze learning in right- and left-handed adults.

This study examined asymmetries in transfer learning on a finger maze as a function of handedness, hand at acquisition and maze orientation at transfer. In both handedness groups, right-hand acquisition enhanced opposite hand performance on an identical and a vertically reversed maze at transfer, relative to a mirror-reversed maze; left-hand acquisition, in turn, enhanced opposite hand transfer on the spatially reversed mazes relative to the identical maze. The findings suggest that different strategies (i.e. verbal versus spatial/motoric) come into play in maze learning depending on the hand used at acquisition (right versus left, respectively) rather than on overall hand dominance.

Adult↗

Hippocampal and prefrontal cortex contributions to learning and memory: analysis of lesion and aging effects on maze learning in rats.

Young adult rats with bilateral lesions to the hippocampus or prefrontal cortex, young operated controls, and normal old rats were tested on two complex mazes in the Hebb-Williams series. Approximately half the animals were previously trained on one of the mazes; the remainder received no previous training. The trained hippocampal rats showed sparing of memory for the general skill of maze learning but poor recall of the specific maze on which they had been previously trained. The opposite pattern was observed in trained prefrontal rats. In contrast, the aged rats' memory for maze-specific and maze-general information was impaired. The results confirmed the importance of the hippocampus for recalling highly specific information and pointed to a possible role for the frontal lobes in learning and remembering nonspecific skill-related information. The generalized deficit of the aged rats indicates that both types of memory were compromised and offers further evidence of frontal lobe and hippocampal dysfunction in normal aging.

Aging↗

Enhanced passive avoidance learning and appetitive T-maze learning with post-trial rewarding hypothalamic stimulation.

Experiments were carried out to investigate the effects of post-trial reinforcing stimulation of the lateral hypothalamus on learning in rats. The reinforcing stimulation was always presented for a duration of 20--30 sec (0.2 sec on/0.8 sec off), and was administered either immediately, 30 sec delayed or 300 sec delayed after exposure to the learning situation. In experiment 1 post-trial stimulation led to improved passive avoidance learning of an alcove-avoidance task when presented 30 sec compared to immediately after the footshock. In Experiment 2 reversal learning of a one-way shuttle-box avoidance task was facilitated by 30 sec delayed, but not 300 sec delayed post-trial reinforcing stimulation. In Experiment 3 appetitive left-right discrimination was investigated using a T-maze task. Thirty sec delayed post-trial reinforcing stimulation presented contingent on errors facilitated learning of this task. Together, the 3 studies provide further support for the hypothesis that reinforcers directly influence labile memory processes (such as short-term memory) and thereby improve learning.

Animals↗

Impairment of maze learning in rats following long-term glucocorticoid treatments.

The present study examined the influence of long-term glucocorticoid treatment on a maze learning task on a radial 8-arm maze in rats. Either 100 mg cholesterol (as a control), or corticosterone, bead was implanted in rats for a period of 3 months, beginning at 12 weeks of age. The effect of this treatment on the maze learning task was evaluated during or 4 weeks after the treatments. In both experiments, corticosterone-implanted rats showed an increase in number of trials to attain at least seven correct choices in the first eight choices in five consecutive trials (P < 0.05). We concluded that long-term glucocorticoid exposure resulted in an impairment of the hippocampal functions, i.e. learning and memory, similar to that found in aged hippocampus.

Animals↗

Intakes of dietary docosahexaenoic acid ethyl ester and egg phosphatidylcholine improve maze-learning ability in young and old mice.

The effect of dietary docosahexaenoic acid (DHA) [22:6 (n-3)] ethyl ester (EE) and egg-phosphatidylcholine (PC) on maze-learning ability in young and old mice was studied. Male Crj:CD-1 mice aged either 3 wk or 14 mo were fed a diet containing 2 g DHA-EE/100 g diet plus 3 g palm oil/100 g diet (DHA-EE Group), 5 g egg-PC/100 g diet (egg-PC Group), 1 g DHA-EE/100 g diet plus 2.5 g egg-PC/100 g diet plus 1.5 g palm oil/100 g diet (DHA-EE + egg-PC Group) or 5 g palm oil/100 g diet (Control Group) for 5 mo. Maze-learning ability was assessed 4 mo after the start of the experiment. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in three trials every 4 d. In trial 2 of young mice, performed on d 4 after the first trial, the DHA-EE group required less (P < 0.05) time to reach the maze exit and DHA-EE and egg-PC groups strayed (P < 0.05) into blind alleys fewer times than the control group. In trial 2 of old mice, the DHA-EE, egg-PC and DHA-EE + egg-PC groups needed less (P < 0.05) time to find the exit and spent a fewer (P < 0.05) number of times in blind alleys than did the control group. The DHA-EE, DHA-EE + egg-PC and egg-PC groups strayed into blind alleys fewer times than the control group in trial 3 of old mice (P < 0.05). Our results suggest that the intake of DHA-EE and the egg-PC diet effectively enhances maze-learning ability and brain functions in old mice.

Aging↗

Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice.

The present study was done to characterize the effects of intracerebroventricular injection of galanin (GAL) on memory processes by observing passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice. An intermediate dose (3 micrograms) of GAL (3 micrograms) significantly decreased step-down latency of passive avoidance response when given 15 min before training, whereas in particular the middle doses (0.3 and 1 microgram) of GAL significantly decreased it when given 15 min before retention tests. However, GAL (0.3-10 micrograms) was ineffective when given immediately after training. Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and 0.03 mg/kg), a cholinergic agonist, significantly inhibited the shortening of step-down latency induced by GAL (0.3 microgram) administered 15 min before retention tests, indicating the involvement of cholinergic dysfunction in the GAL (0.3 microgram)-induced shortening of step-down latency. In contrast, GAL (0.3-3 micrograms) failed to influence transfer latency in elevated plus-maze learning or percent alternation in spontaneous alternation performance. These results suggest that the activation of cholinergic neurons improves memory dysfunctions induced by GAL, which primarily impairs retrieval processes of memory. The lack of effects of GAL on the elevated plus-maze learning and spontaneous alternation performance may result from the selective effects of GAL in different learning paradigms.

Amino Acid Sequence↗

Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats.

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid-induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of neurosteroids and benzodiazepines on food consumption and learning and memory processes.

Analysis of Variance↗