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PubMed1984

Spatial learning and motor deficits in aged rats.

Young (3 months) and aged (24 months) rats were compared on a range of behavioural tests. The aged animals were impaired in their acquisition of a spatial learning task in the Morris water maze, as well as showing deficits in motor coordination, swimming efficiency, and spontaneous locomotion and exploration in an open field. Qualitative observation and correlation analyses indicated that the aged group was heterogeneous in the degree of impairments manifested by the individual animals, and suggested that the development of impairments may progress with aging at different rates in the various tasks and possibly in different underlying neuroanatomical systems.

Aging↗
PubMed2001

Longitudinal analysis of motor activity and coordination, anxiety, and spatial learning in mice with altered blood pressure.

Mice with either high or low blood pressure (BP) were compared to normotensive controls at 2 and 12 months of age for motor activity, equilibrium, anxiety, and spatial learning. Irrespective of age, high BP mice were more active in an open field than normotensive controls, whereas low BP mice were hypoactive at 2 months of age. High BP mice had a higher number of entries and a longer duration of visits in the open arms, a higher open arm/total arm ratio, a longer duration for the first visit into an open arm, and lower latencies before entering the first open arm than controls in the elevated +-maze, indicative of reduced anxiety. Reduced levels of anxiety were also displayed by low BP mice for the duration of the first open arm visit (both age groups) and for the time spent in the open arms (older group). In the motor coordination test (coat-hanger), high BP mice had higher two-paw movement time and reached the top of the apparatus on fewer occasions than controls. Both groups with abnormal BP values were deficient during visuomotor guidance in the water maze. These results indicate strain-, age-, and test-specific abnormalities in mice with uncontrolled hypertension or hypotension.

Aging↗
PubMed1999

Dissociating context and space within the hippocampus: effects of complete, dorsal, and ventral excitotoxic hippocampal lesions on conditioned freezing and spatial learning.

Rats with complete excitotoxic hippocampal lesions or selective damage to the dorsal or ventral hippocampus were compared with controls on measures of contextually conditioned freezing in a signaled shock procedure and on a spatial water-maze task. Complete and ventral lesions produced equivalent, significant anterograde deficits in conditioned freezing relative to both dorsal lesions and controls. Complete hippocampal lesions impaired water-maze performance; in contrast, ventral lesions improved performance relative to the dorsal group, which was itself unexpectedly unimpaired relative to controls. Thus, the partial lesion effects seen in the 2 tasks never resembled each other. Anterograde impairments in contextual freezing and spatial learning do not share a common underlying neural basis; complete and ventral lesions may induce anterograde contextual freezing impairments by enhancing locomotor activity under conditions of mild stress.

Analysis of Variance↗
PubMed1989

Recovery of spatial learning deficits after decay of electrically induced synaptic enhancement in the hippocampus.

A widespread interest in a long-lasting form of synaptic enhancement in hippocampal circuits has arisen largely because it might reflect the activation of physiological mechanisms that underlie rapid associative learning. As its induction normally requires the 'Hebbian' association of activity on a number of input fibres, we refer to the process as long-term enhancement (LTE) rather than long-term potentiation (LTP), to emphasize its distinction from the ubiquitous, non-associative 'potentiation' phenomena that occur at most synapses, including those exhibiting LTE. Among other evidence that LTE might actually have a role in associative memory is the demonstration that repeated high-frequency stimulation, which saturated the inducible LTE, caused a severe deficit in spatial learning, although it had no effect on well established spatial memory. These results were consistent with a widespread view that information need only temporarily be stored in the hippocampal formation in order for long-term memories to be established in neocortical circuits. In this context, it is important to understand whether the possible underlying synaptic changes are of a permanent character, or are relatively transient. A second question is whether the actual cause of the observed learning deficit is the distruption of the synaptic weight distribution, and/or the limitation of further synaptic change, which presumably results from experimental saturation of the LTE mechanism. Alternatively, the deficit could be a consequence of some unobserved secondary effect of the high-frequency electrical stimulation. Here we demonstrate that learning capacity recovers in about the same time that it takes LTE to decay, which strongly favours the first possibility and supports the idea that LTE-like processes actually underlie associative memory.

Animals↗
PubMed2003

Comparison of the effects of early handling and early deprivation on conditioned stimulus, context, and spatial learning and memory in adult rats.

Effects of manipulations of the rat pup-dam relationship on affective learning and memory in adulthood have received scant systematic investigation. The authors previously described how early handling (EH; 15 min isolation/day) and early deprivation (ED; 4 hr isolation/day) exert similar effects on spontaneous adult affect (open-field behavior, acoustic startle, endocrine stress response) relative to nonhandling (NH; C. R. Pryce, D. Bettschen, N. I. Bahr, & J. Feldon, 2001). The present study demonstrates that both EH and ED adults exhibit enhanced active avoidance relative to NH adults. Fear-conditioned context and conditioned stimulus (CS) freezing were unaffected in both EH and ED, but stress hormone responses to the CS were reduced in EH males and ED females relative to NH. In the water maze, ED adults exhibited enhanced spatial learning and memory relative to NH.

Adrenocorticotropic Hormone↗
PubMed1994

Sun compass-based spatial learning impaired in homing pigeons with hippocampal lesions.

The hippocampal formation is known to be critical for spatial cognition, for example, regulating the learning of environmental maps. But how is a spatial map learned, and what is the role of the hippocampal formation in the learning process? The sun compass is perhaps the most ubiquitous, naturally occurring spatial orientation mechanism found in the animal kingdom. The sun compass may also serve as a directional reference that supports spatial learning. We report that homing pigeons with hippocampal lesions were unable to use the sun compass to learn the directional location of food in an outdoor, experimental arena. Homing pigeons with lesions of the caudal neostriatum readily learned the same task, and showed appropriately shifted directional responses following a clock-shift manipulation demonstrating that they were indeed using the sun compass to learn the task. Finally, both hippocampal and control lesioned birds quickly learned a procedurally similar task where a color cue identified the location of food in the same experimental arena. The results indicate that hippocampal lesions impair sun compass use in the context of learning. As such, the results support the hypothesis that the importance of the hippocampal formation in spatial cognition may be related to its participation in a neural process in which information from a directional reference, in this case the sun compass, is used to learn the directional relationship among stimuli in space.

Animals↗
PubMed2004

Prolonged in utero meconium exposure impairs spatial learning in the adult rat. Central Prize Award.

OBJECTIVE: The purpose of this study was to examine the effects of prolonged in utero meconium exposure on adult learning and memory, as measured by the Morris water maze. STUDY DESIGN: Timed pregnant Long-Evans rats were studied. On gestational day 20 (term, 21 days of gestation), laparotomy was performed, and each maternal animal received an injection of clear amniotic fluid or meconium-stained amniotic fluid into each gestational sac. The laparotomy incision was closed, and the animals received postoperative monitoring through delivery. On postnatal days 145 to 148, the offspring underwent Morris water maze testing. The mean (+/-SEM) for the latency time was reported for each day's trial and compared between groups. RESULTS: There were significant differences between meconium-stained amniotic fluid group and clear amniotic fluid group in the mean time to platform on day 1 (82.7 +/- 1.8 seconds vs 75.9 +/- 3.0 seconds; P=.04), day 2 (60.5 +/- 3.5 seconds vs 47. 8 +/- 4.6 seconds; P=.03), and day 3 (56.5 +/- 4.5 seconds vs 34.7 +/- 4.4 seconds; P=.001). However, there were no differences on days 4 and 5. There were also no differences between recall and response learning trials that were done after a 12-day retention period. CONCLUSION: In the absence of hypoxia or infection, prolonged in utero meconium exposure is associated with a delay of spatial learning in the adult rat.

Analysis of Variance↗
PubMed2002

Effect of prenatal administration of haloperidol, risperidone, quetiapine and olanzapine on spatial learning and retention in adult rats.

The typical antipsychotic haloperidol and atypical antipsychotics olanzapine, quetiapine and risperidone were administered to pregnant Sprague-Dawley dams in the drinking water from Days 8 to 18 of gestation. When the offspring reached adulthood (2 months), spatial learning and short-term retention were examined using the radial arm maze. Results showed that prenatal administration of haloperidol, risperidone and quetiapine impaired learning but only haloperidol and risperidone disrupted short-term retention.

Animals↗
PubMed2006

Anastrozole improved testosterone-induced impairment acquisition of spatial learning and memory in the hippocampal CA1 region in adult male rats.

Neurohormones like testosterone and estrogen have an important role in learning and memory. Many biological effects of androgens in the brain require the local conversion of these steroids to an estrogen. The current research has conducted to assess the effect of testosterone, estrogen and aromatase inhibitor (anastrozole) on spatial discrimination of rats, using Morris water maze and also the pathway of the effect of testosterone by using anastrozole. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and divided into 15 groups. Different groups received DMSO 0.5 microl and DMSO 0.5 microl + DMSO 0.5 microl as control groups and different doses of testosterone enanthate (TE) (20, 40 and 80 microg/0.5 microl), estradiol valerat (EV) (1, 2.5, 5, 10, and 15 microg/0.5 microl), anastrozole (An) (0.25, 0.5, 1 microg/0.5 microl), TE 80 microg/0.5 microl + anastrozole 0.5 microg/0.5 microl and EV 15 microg/0.5 microl + anastrozole 0.5 microg/0.5 microl all days before training. TE and EV were injected 30-35 min before training and anastrozole was injected 25-30 min before training. Our results have shown both TE 80 microg/0.5 microl and EV 15 microg/0.5 microl groups increase in escape latency and traveled distance to find invisible platform. Also we have shown that anastrozole dose dependently decreases escape latency and traveled distance. We resulted that both TE and EN impaired acquisition of spatial learning and memory but anastrozole improved it. Anastrozole also could be buffered TE-induced impairment effect but not EV.

Analysis of Variance↗
PubMed1993

Subchronic MK-801 treatment to juvenile rats attenuates environmental effects on adult spatial learning.

Treatment with the non-competitive NMDA receptor blocker MK-801 (0.16 mg/kg), given to juvenile rats before and after the exposure to an enriched environment on alternate days for 4 weeks, attenuated the improvements in spatial learning and open field adaptation which resulted from such environmental stimulation. Drug treatment affected the consolidation of experiences as an injection given after exposure to the enriched environment was needed to demonstrate this effect. In addition, MK-801 administration diminished the adverse effect of stimulus deprivation-the slow learning rate normally seen in rats housed in impoverished environment. Radioligand binding studies showed that drug treatment decreased [3H]MK-801 binding sites in cortex. The learning, activity and receptor binding effects were measured 4 months from cessation of the drug treatment and environmental manipulation. The results support the role of NMDA receptors in mediating cognitive changes associated with environmental stimulation.

Animals↗
PubMed2002

Comparisons between C57BL/6J and A/J mice in motor activity and coordination, hole-poking, and spatial learning.

The C57BL/6J (B6) inbred mouse strain was compared to the A/J inbred strain for motor activity in an open-field, exploration of a hole-board, motor coordination in the coat-hanger test, and spatial learning in the Morris water maze. B6 mice displayed a higher number of segment crossings in the open-field and of hole-poking responses than A/J mice. The performance of B6 mice was superior to that of A/J mice not only in the submerged but also in the visible platform version of the Morris water maze. By contrast to their hypoactivity, the A/J strain had shorter movement times in the coat-hanger test, indicating faster motor speed, although the groups did not differ in latencies before falling. These results indicate that recombinant inbred or congenic strains derived from B6 and A/J mice offer considerable potential for discerning the genetic basis of several behavioral phenotypes.

Animals↗
PubMed2005

Rehabilitative training tasks improve spatial learning impairment in the water maze following hypoxic-ischemic insult in neonatal rats.

We recently reported that hypoxic-ischemic (HI) insult to the brain of 7-d-old rats resulted in a slowly progressive learning and memory disability, which started at around 5 wk after HI, a time frame that is representative of human adolescence. The purpose of the present study was to examine whether physical or mental exercises can prevent this late-onset, slowly progressing disability. Wistar rats were subjected to left carotid ligation followed by 2 h of hypoxic stress (8% O2 and 92% N(2) at 33 degrees C). Sham-control rats were subjected to the same procedure without ligation and hypoxic stress. Six weeks after the HI, the animals were divided into four groups: pretraining control, no training control, pretraining HI, and no training HI groups. We used the plus maze, eight-arm radial maze, and choice reaction time task as the rehabilitative training. Sixteen weeks after the HI, the water maze task was performed over 5 d to evaluate spatial learning ability; thereafter, cerebral morphology of the animals was examined. There were no differences in swimming length and latency between the pretraining control and no training control groups. Swimming length and latency in the pretraining HI group were significantly shorter and swifter than those in the no training HI group. The infarct areas on the left cerebral hemisphere were equivalent between pretraining HI and no training HI groups at each sectional slice. Rehabilitative training tasks prevented the neonatal HI-induced late-onset slowly progressive learning and memory disability.

Animals↗
PubMed1996

Acute exposure to power-frequency magnetic fields has no effect on the acquisition of a spatial learning task by adult male mice.

A series of four experiments was performed to determine whether acute exposure to a range of 50 Hz magnetic fields had any effect on a learning task in adult male CD1 mice. A radial-arm maze placed within the bore of an electromagnet was used to assess spatial discrimination learning for food reward. Subjects were reduced to 85% of their free-feeding weight and were placed in the maze for up to 15 minutes each day for 10 days. Performance of the task was measured by using maximum likelihood techniques to calculate the probability that an animal would not reenter any given arm of the maze. Experimental subjects were exposed to a vertical, 50 Hz sinusoidal magnetic field at 5 microT, 50 microT, 0.5 mT, or 5.0 mT (rms). Control subjects were exposed only to a background time-varying field of less than 50 nT and the ambient static field of about 40 microT. The variation in the applied magnetic field was less than 5% except at the ends of the arms, where it approached 10%. It was found that all eight groups of subjects (n = 10 in all cases) showed similar increases in performance with testing, and the acquisition curve for each group of experimental subjects was not significantly different from that of their control group (P > 0.05 in all cases). It was concluded that exposure had no effect on learning at any flux density. This result is contrary to the findings of a number of preliminary studies, although other studies have reported that magnetic fields do not affect spatial learning in adult male rodents. It is possible that differences between experimental conditions might explain some of this apparent discrepancy.

Animals↗
PubMed1990

Muscimol injections in the medial septum impair spatial learning.

These experiments examined the role of GABAergic systems in modulating septohippocampal cholinergic influences on learning. Microinjections of the GABA(A) agonist muscimol (0.5, 1.0 or 5.0 nmol) or physiological saline were administered (0.5 microliters) into the medial septum of rats via chronically implanted cannulae just prior to daily training in the Morris water maze spatial learning task. The animals received 3 training trials on each of 4 days. The escape latencies of rats trained with a submerged escape platform at a fixed location were significantly shorter than those trained with a randomly located platform. Rate of learning of the fixed location was significantly impaired in rats given pretraining muscimol injections in the medial septum at doses (1.0 and 5.0 nmol) that significantly reduced hippocampal high-affinity choline uptake (HACU). Analyses of responses on a probe trial with no pretraining injections and no platform revealed that, in comparison with controls, animals that had received muscimol prior to each training session were likely to swim in the region where the platform had been located. The finding that muscimol-injected rats were subsequently able to learn the task when trained without muscimol injections indicates that the acquisition impairment was not due to a lasting effect of the drug injections. Our results are consistent with the view that the septal GABAergic modulation of the septohippocampal cholinergic pathway is involved in regulating the acquisition of spatial information.

Animals↗
PubMed1991

Decreased glutamate release correlates with elevated dynorphin content in the hippocampus of aged rats with spatial learning deficits.

The effects of aging on extracellular glutamate and tissue dynorphin content in the hippocampus were examined in Fischer-344 rats. Young adult (4-month-old) and aged (24-month-old) rats were trained to find a hidden platform in the Morris water task. Aged rats were unable to acquire the spatial learning task as rapidly as young controls. Following behavioral testing, an in vivo microdialysis perfusion method was used to determine extracellular glutamate levels in the hippocampus. There was a 25-35% reduction in extracellular glutamate concentration in both dorsal and ventral hippocampus of aged rats compared to young rats, in the absence of any change in tissue glutamate levels. Radioimmunoassay showed an increase in dynorphin A(1-8)-like immunoreactivity [DYN-A(1-8)LI] in both dorsal and ventral hippocampus, but not striatum, of aged rats. Immunocytochemistry indicated that this increase was localized to the dentate granule cells and mossy fibers. Furthermore, among the aged rats the increase in DYN-A(1-8)LI was inversely correlated with the decrease in extracellular glutamate. These results suggest that the disregulation of dynorphin observed in cognitively impaired aged rats is related to reduced excitatory transmission within the hippocampal formation.

Aging↗