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PubMed2026

Dual-contrastive learning for spatial domain identification in spatial transcriptomics with STAMGC.

Spatial transcriptomics (STs) have become a valuable approach for understanding the growth and development of organisms. Despite the recent emergence of numerous ST models, accurately identifying spatial domains remains challenging owing to the trade-off between preserving local details and reducing noise. Here, we introduce STAMGC, which is a dual-contrastive learning framework built upon graph convolutional networks. This model leverages regional and topological contrastive learning to jointly optimize the model, effectively reducing the noise in spatial domain identification and enhancing the extraction of detailed features. In this study, Gaussian smoothing, originally developed in the image processing field, is introduced to process ST data, providing a foundation for region-level contrastive learning by mitigating spatial discontinuities of gene expression signals. Experimental results indicate that STAMGC outperforms existing methods across multiple data sets according to comprehensive evaluations. Furthermore, STAMGC not only identifies finer structures in the mouse brain but also brings new discoveries for human breast cancer research.

Journal Article↗
PubMed1999

Local inhibition of hippocampal nitric oxide synthase does not impair place learning in the Morris water escape task in rats.

Recent studies have provided evidence that nitric oxide (NO) has a role in certain forms of memory formation. Spatial learning is one of the cognitive abilities that has been found to be impaired after systemic administration of an NO-synthase inhibitor. As the hippocampus has a pivotal role in spatial orientation, the present study examined the role of hippocampal NO in spatial learning and reversal learning in a Morris task in adult rats. It was found that N omega-nitro-L-arginine infusions into the dorsal hippocampus affected the manner in which the rats were searching the submerged platform during training, but did not affect the efficiency to find the spatial location of the escape platform. Hippocampal NO-synthase inhibition did not affect the learning of a new platform position in the same water tank (i.e. reversal learning). Moreover, no treatment effects were observed in the probe trials (i.e. after acquisition and after reversal learning), indicating that the rats treated with N omega-nitro-L-arginine had learned the spatial location of the platform. These findings were obtained under conditions where the NO synthesis in the dorsal hippocampus was completely inhibited. On the basis of the present data it was concluded that hippocampal NO is not critically involved in place learning in rats.

Animals↗
PubMed1999

The influences of sex, rearing environment, and neonatal choline dietary supplementation on spatial and nonspatial learning and memory in adult rats.

The potential facilitative effects of early environmental enrichment and perinatal choline chloride dietary supplementation on male and female adult rats' learning and memory were examined using a "stimulus-elicited investigative," and a social/observational learning-cued spatial memory paradigm. Male and female animals were either maintained in a standard lighted colony (SC) or were given supplementary exposure to a complex environment (EC) for 2 hr daily from 24-90 days of age. In each case, half of the animals were exposed to the choline supplementation both prenatally and postnatally for 24 days. In one paradigm, the 90-day-old EC rats were found to be significantly more responsive than SC rats to each change in the spatial relationships of objects contained in an open field. Neither sex nor early diet of the animals were much of a factor in the investigative behavior observed. In the second paradigm, the effects of the perinatal choline diet did interact with those of sex and postnatal environment to alter the impact of social/observational experience on the acquisition and memory of place in the water maze. The choline-treated EC males were the most influenced by their experience seeing a demonstrator swim to a platform location. The present study provides some further insight into the scope of the long-term functional enhancements produced by perinatal choline supplementation and EC in male and female animals and relates these effects to common modifications to targets of cholinergic basal forebrain systems.

Animals↗
PubMed1992

Changes in PKC gamma immunoreactivity in mouse hippocampus induced by spatial discrimination learning.

In the present study, we examined changes in immunoreactivity (ir) for the gamma-isoform of protein kinase C (PKC gamma) in mouse hippocampus in relation to spatial memory processes employing the monoclonal antibody 36G9 raised against purified PKC gamma. Learning and memory were assessed by performance in a free-choice spatial pattern paradigm in a hole board in which the animals learned the pattern of 4 baited holes out of 16 holes. Adult male house mice were used, divided in four groups. Three control groups were formed: group N, naive (blank controls); group H, habituated (animals were for 5 consecutive days introduced to the hole board with all holes baited); and group PT, pseudotrained (animals were for 13 consecutive days introduced to the hole board with all holes baited). The T (trained) group was for 5 consecutive days introduced to the hole board with all holes baited (similar to the H and PT groups) followed by 8 successive days with only four holes baited in a fixed pattern. Behaviorally, following the first 5 d, the PT group crossed the hole board randomly, whereas the T group gradually learned to orientate in the hole board. The mice were killed 24 hr after the last performance. A shift in 36G9-ir appeared from the cell somata to the dendrites of hippocampal principal neurons when comparing the H and PT group, respectively. In contrast, the T group showed strong PKC gamma-ir in both cell somata and dendrites, which clearly exceeded that of the H and PT mice. In this way, 36G9-ir reveals the physiologically activated neurons involved in hole board learning.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Prenatal zinc treatment at the time of acute ethanol exposure limits spatial memory impairments in mouse offspring.

Zinc (Zn) treatment given together with acute ethanol in early pregnancy has previously been demonstrated to protect against physical birth abnormalities in mice. The current study examined whether this Zn treatment (s.c. injection) can also prevent the more subtle cognitive impairments caused by ethanol exposure in early pregnancy. Pregnant C57BL/6J dams were injected with saline (0.85% wt/vol NaCl) or 25% ethanol (0.015 mL/g body weight) intraperitoneally at 0 and 4 h on gestational d (GD) 8. ZnSO4 (2.5 microg Zn/g at 0 h) treatment was administered by s.c. injection immediately following ethanol treatment. Offspring were randomly selected from litters for each of the three treatment groups and were tested at 55 and 70 d of age using a cross-maze water escape task for spatial learning and memory impairments consecutively. No differences were observed between treatments for the spatial learning task. However, young adult mice exposed to ethanol in utero demonstrated impaired spatial memory, with a decrease in correct trials and increased escape latency and incorrect entry measurements, compared with saline-treated controls. In comparison, offspring given s.c. Zn treatment at the time of ethanol exposure were not cognitively impaired, performing at the same level as control mice in the cross-maze escape task. These findings indicate that critically timed Zn administration can limit spatial memory impairments caused by ethanol exposure in early pregnancy.

Animals↗
PubMed2000

Hippocampal expression of the orphan nuclear receptor gene hzf-3/nurr1 during spatial discrimination learning.

The immediate-early gene hzf-3, also known as nurr1, is a member of the inducible orphan nuclear receptor family and is one candidate in the search for genes associated with learning and memory processes. Here we report that acquisition of a spatial food search task is accompanied by elevated levels of hzf-3 mRNA in the hippocampus. Adult male Long-Evans rats were handled, food-restricted, and allowed to habituate to the maze prior to training. During acquisition, rats were given one training session per day for 5 days. Each training session consisted of five trials in which animals searched the maze for food located in 4 of 16 holes in the floor of the maze. Training resulted in spatial acquisition of the task. Northern blot analysis showed significant increases in hippocampal hzf-3 mRNA 3 h after training in the maze. Next, brains were obtained from Naive, Habituated, Day 1, Day 3, and Day 5 animals and processed for in situ hybridization. The results showed significant increases of hzf-3 mRNA in CA1 and CA3 subregions of the dorsal hippocampus during acquisition of the task. We conclude that expression of the hzf-3 gene in the brain is associated with long-term spatial memory processes. The present results are the first to implicate an orphan nuclear receptor in long-term information storage in the hippocampus.

Animals↗
PubMedDate not supplied

Evaluation of neonatal exposure to cocaine on learning, activity, startle, scent marking, immobility, and plasma cocaine concentrations.

Prenatal cocaine treatment produces equivocal effects on spatial learning and memory; however, no data are available on neonatal treatment as a model of human third-trimester exposure. Sprague-Dawley rats were treated on postnatal days (P) 1-10 or 11-20 with cocaine (15 mg/kg x 4 per day at 2-h intervals) or saline (P1-P20) and evaluated as adults in the Morris water maze and on tests of activity, startle, scent marking, swimming immobility, and sequential learning. Neonatal cocaine had no effect on mortality; however, early treatment reduced body weight, whereas later treatment did not. Neonatal cocaine had no effects on exploratory activity, swimming ability, sequential learning, multiday activity rhythms, scent marking, or swimming immobility, but augmented acoustic startle amplitude in the early-treated group. Neonatal cocaine also produced an interaction on spatial learning in which the cocaine early-treated males performed slightly more efficiently than controls. Plasma cocaine concentrations were significantly higher in the early-treated group than the later-treated group despite receiving the same weight-adjusted doses. It was concluded that neonatal cocaine, when administered during a stage of brain development analogous to human third trimester, induces few behavioral effects based on the assessments used in this study.

Animals↗
PubMed1999

Specificity of memory deficits after right or left temporal lobectomy.

An impairment of verbal memory has consistently been associated with resection of the left dominant temporal lobe, whereas non-verbal memory deficits have been less reliably observed following resection of the right temporal lobe. Such a dissociation may be due to material-specific differences of processing between verbal and non-verbal information. Alternatively, the influence of the left and right limbic structures may vary according to the stage of memory processing. The aim of the study was to test these hypotheses by comparing verbal and spatial learning in patients with left or right temporal lobe resection for intractable epilepsy, using verbal and visuospatial memory tasks with the same design: control of encoding, multiple trial learning, free and cued recall, short and long delays. The results showed: (1) a similar pattern of learning and recall in the two groups; (2) a higher performance in spatial learning for patients with left temporal lobe resection and in verbal learning for patients with right temporal lobe resection; (3) material-specific effects characterized by a higher sensitivity to cues in the verbal domain and a better retention of information during delays in the spatial domain. These results suggest parallel processing of the two temporal lobes at the various memory stages, rather than an interaction between memory stage and side of the lesion similar to that already proposed for the frontal lobes. They also confirm a double dissociation between verbal/spatial information processing and side of temporal lobe resection.

Adult↗
PubMed1999

Effects of prenatal zidovudine treatment on learning and memory capacities of preweanling and young adult mice.

The present study analyzed the short and long-term effects of prenatal zidovudine (AZT) exposure on learning and memory capacities of CD-1 mice. Two tasks normally used in rodents were used, namely a passive avoidance step-through task and a Morris navigation task. AZT (0, 0.4, and 0.8 mg/ml) was administered via drinking water to pregnant CD-1 females from day 10 of gestation to delivery. Data on reproductive performance, such as gestation length, litter size, and pup mortality were collected. Avoidance learning in the offspring was tested on postnatal day (PND) 15, while spatial learning performances in the Morris water maze were obtained on PND 45. Retention of the passive avoidance response was mildly impaired in the offspring exposed to the 0.8 mg/ml AZT solution, whereas spatial learning on PND 45 was unaffected.

Animals↗
PubMedDate not supplied

Knockdown of Nurr1 in the rat hippocampus: implications to spatial discrimination learning and memory.

Nurr1 expression is up-regulated in the brain following associative learning experiences, but its relevance to cognitive processes remains unclear. In these studies, rats initially received bilateral hippocampal infusions of control or antisense oligodeoxynucleotides (ODNs) 1 h prior to training in a holeboard spatial discrimination task. Such pre-training infusions of nurr1 antisense ODNs caused a moderate effect in learning the task and also impaired LTM tested 7 d later. In a second experiment, ODN infusions were given immediately after the animals had received two sessions of training, during which all animals showed normal learning. Although antisense treated rats were significantly impaired during the post-infusion stages of acquisition of the task, no group differences were observed during the LTM test given 7 d later. These animals were subjected 3 d later to reversal training in the same maze in the absence of any additional treatments. Remarkably, rats previously treated with antisense ODNs displayed perseveration: The animals were fixated with the previously learned pattern of baited holes, causing them to be significantly impaired in the extinction of acquired spatial preferences and future learning. We postulate that Nurr1 function in the hippocampus is important for normal cognitive processes.

Analysis of Variance↗
PubMed2005

Sleep restriction suppresses neurogenesis induced by hippocampus-dependent learning.

Sleep deprivation impairs hippocampal-dependent learning, which, in turn, is associated with increased survival of newborn cells in the hippocampus. We tested whether the deleterious effects of sleep restriction on hippocampus-dependent memory were associated with reduced cell survival in the hippocampus. We show that sleep restriction impaired hippocampus-dependent learning and abolished learning-induced neurogenesis. Animals were trained in a water maze on either a spatial learning (hippocampus-dependent) task or a nonspatial (hippocampus-independent) task for 4 days. Sleep-restricted animals were kept awake for one-half of their rest phase on each of the training days. Consistent with previous reports, animals trained on the hippocampus-dependent task expressed increased survival of newborn cells in comparison with animals trained on the hippocampus-independent task. This increase was abolished by sleep restriction that caused overall reduced cell survival in all animals. Sleep restriction also selectively impaired spatial learning while performance in the nonspatial task was, surprisingly, improved. Further analysis showed that in both training groups fully rested animals applied a spatial strategy irrespective of task requirements; this strategy interfered with performance in the nonspatial task. Conversely, in sleep-restricted animals, this preferred spatial strategy was eliminated, favoring the use of nonspatial information, and hence improving performance in the nonspatial task. These findings suggest that sleep loss altered behavioral strategies to those that do not depend on the hippocampus, concomitantly reversing the neurogenic effects of hippocampus-dependent learning.

Animals↗
PubMed1997

A mouse model for the learning and memory deficits associated with neurofibromatosis type I.

Neurofibromatosis type I (NF1) is one of the most commonly inherited neurological disorders in humans, affecting approximately one in 4,000 individuals. NF1 results in a complex cluster of developmental and tumour syndromes that include benign neurofibromas, hyperpigmentation of melanocytes and hamartomas of the iris. Some NF1 patients may also show neurologic lesions, such as optic pathway gliomas, dural ectasia and aqueduct stenosis. Importantly, learning disabilities occur in 30% to 45% of patients with NF1, even in the absence of any apparent neural pathology. The learning disabilities may include a depression in mean IQ scores, visuoperceptual problems and impairments in spatial cognitive abilities. Spatial learning has been assessed with a variety of cognitive tasks and the most consistent spatial learning deficits have been observed with the Judgement of Line Orientation test. It is important to note that some of these deficits could be secondary to developmental abnormalities and other neurological problems, such as poor motor coordination and attentional deficits. Previous studies have suggested a role for neurofibromin in brain function. First, the expression of the Nf1 gene is largely restricted to neuronal tissues in the adult. Second, this GTPase activating protein may act as a negative regulator of neurotrophin-mediated signalling. Third, immunohistochemical studies suggest that activation of astrocytes may be common in the brain of NF1 patients. Here, we show that the Nf1+/- mutation also affects learning and memory in mice. As in humans, the learning and memory deficits of the Nf1+/- mice are restricted to specific types of learning, they are not fully penetrant, they can be compensated for with extended training, and they do not involve deficits in simple associative learning.

Acoustic Stimulation↗
PubMed2006

Long-term behavioral and developmental consequences of pre- and perinatal nicotine.

Research has shown that cigarette use during pregnancy can result in increased fetal mortality, sudden infant death syndrome, and behavioral and attentional disorders during childhood. Neurochemical and behavioral consequences of prenatal nicotine exposure have been well documented although few studies have examined long-term behavioral consequences that persist into adulthood. In this study, fifty-eight male and female Long-Evans rats were exposed to chronic nicotine prenatally and postnatally via subcutaneous infusions (0.96 mg/kg/day) in the dam. Nicotine exposure continued in the pups via maternal milk until the dams' osmotic mini-pumps became exhausted at approximately postnatal day (P) 11. At weaning, animals were group housed until behavioral testing at P60 to assess spatial learning and memory in the Morris water maze (MWM). Mild deficits in spatial learning were observed in nicotine-exposed females. These behavioral differences were accompanied by significant reduction in weight gain of nicotine-exposed females beginning at puberty, suggesting a hormonal interaction. Long-term effects of nicotine exposure were less striking in males. Nicotine-exposed males had significantly slower swim speeds than controls, but latency to reach the hidden platform was equal between groups by the conclusion of testing. Weight gain in males did not differ between groups as a result of prenatal nicotine exposure.

Animals↗
PubMed2005

REM sleep deprivation affects extinction of cued but not contextual fear conditioning.

Previous research has demonstrated that rapid eye movement (REM), or paradoxical, sleep deprivation can interfere with the retention of certain types of learning tasks, particularly spatial learning. The present study investigated the effects of 6 h of REM sleep deprivation on the retention and extinction of both cued and contextual conditioning tasks in rats. Sleep-deprived animals showed normal retention of both types of conditioning tasks but retarded extinction of the cued task and a trend toward attenuated spontaneous recovery of the contextual task. The results provide further evidence for the involvement of REM sleep in learning and memory processes.

Acoustic Stimulation↗
PubMed2000

Three months of chronic ethanol administration and the behavioral outcome of rats after lateral fluid percussion brain injury.

This study examined the effects of 3 months of chronic ethanol administration (CEAn) on the behavioral outcome in rats after lateral fluid percussion (FP) brain injury. Rats were given either an ethanol liquid diet (ethanol diet groups) or a pair-fed isocaloric sucrose control diet (control diet groups) for 3 months. Then, rats from both diet groups were subjected to either lateral FP brain injury of moderate severity (1.8 atm) or to sham operation. Postinjury behavioral measurements revealed that brain injury caused significant spatial learning disability in both diet groups. There were no significant differences in spatial learning ability in the sham or brain-injured animals between the control and ethanol diets. However, a trend towards cognitive impairment in the sham animals and a trend towards reduced deficits in the brain-injured animals were observed in the ethanol diet group. Histologic analysis of injured animals from both diet groups revealed similar extents of ipsilateral cortical and hippocampal CA3 damage. These results, in general, suggest that 3 months of CEAn does not significantly alter the behavioral and morphologic outcome of experimental brain injury.

Alcohol Drinking↗
PubMed2006

Altered hippocampus synaptic function in selenoprotein P deficient mice.

Selenium is an essential micronutrient that function through selenoproteins. Selenium deficiency results in lower concentrations of selenium and selenoproteins. The brain maintains it's selenium better than other tissues under low-selenium conditions. Recently, the selenium-containing protein selenoprotein P (Sepp) has been identified as a possible transporter of selenium. The targeted disruption of the selenoprotein P gene (Sepp1) results in decreased brain selenium concentration and neurological dysfunction, unless selenium intake is excessive However, the effect of selenoprotein P deficiency on the processes of memory formation and synaptic plasticity is unknown. In the present studies Sepp1(-/-) mice and wild type littermate controls (Sepp1(+/+)) fed a high-selenium diet (1 mg Se/kg) were used to characterize activity, motor coordination, and anxiety as well as hippocampus-dependent learning and memory. Normal associative learning, but disrupted spatial learning was observed in Sepp1(-/-) mice. In addition, severe alterations were observed in synaptic transmission, short-term plasticity and long-term potentiation in hippocampus area CA1 synapses of Sepp1(-/-) mice on a 1 mg Se/kg diet and Sepp1(+/+) mice fed a selenium-deficient (0 mg Se/kg) diet. Taken together, these data suggest that selenoprotein P is required for normal synaptic function, either through presence of the protein or delivery of required selenium to the CNS.

Journal Article↗