Short-term Spatial Memory Research Articles

The effect of age on visuo-spatial short-term memory in family dogs

Decline in the visuo-spatial memory domain may be an early marker for cognitive decline and has a relevant impact on animal welfare. Current research on visuo-spatial memory in family dogs is often limited byfactors such as the need of extensive pre-training, limited attention to co-occurring medical conditions, a focus on laboratory dogs, or low sample size. Therefore, we aimed to develop a test that relies on visuospatialshort-term memory, may be performed in a short time, and does not require explicit training. We tested a large sample of young and old dogs, finding that young dogs were more likely to perform correctly, although performance decreased with consecutive trials in both age groups. However, groups did not vary in the severity of mistakes. This task represents the first measure of dogs’ age-related decline of short-term spatial memory that does not require explicit training. The test could potentially be used in veterinary behaviour contexts to monitor cognitive changes in ageing dogs, utilizing a simple binary measure ofsuccess.

Glucocorticoid receptor activation selectively influence performance of Wistar rats in Y-maze

Glucocorticoid receptors (GR) are ubiquitously expressed in metazoans. Different and contrasting phenotypes have been reported upon their activation. This study investigated the behavioral phenotypes characteristic of GR stimulation in male Wistar rats. Rats in each of the four groups of rats received one of the following treatments: distilled water (control) or one of three doses of dexamethasone (treatment) injected intraperitoneally for 7 days. The Rats were afterwards subjected to the Y maze, the elevated plus maze (EPM), the Morris water maze (MWM), and the novel object recognition (NOR) test. At the end of the study, the animals were anesthetized and neural activity from the prefrontal cortex recorded. Blood was collected via cardiac puncture to evaluate the levels of plasma insulin and glucose, and the prefrontal cortexes excised to determine the levels of insulin, markers of oxidative stress, and calcium in the homogenate.This study showed that treatment with dexamethasone significantly reduced the total and percentage alternation in the Y maze, but had no significant effect on object recognition in the NOR test, long-term and short-term spatial memory in the MWM, or anxiety-like behavior in the EPM. Plasma and brain insulin and calcium levels were elevated moderately following treatment with the lowest dose of dexamethasone. All doses of dexamethasone decreased brain superoxide dismutase and increased lactate dehydrogenase levels. No significant change in neural activity was observed.This study shows that activation of glucocorticoid receptors differentially affects different behavioral paradigms and provides evidence for a role for glucocorticoids in mediating insulin function in the brain.

Effects of cordycepin on spontaneous alternation behavior and adenosine receptors expression in hippocampus

Cordycepin, an adenosine analogue, has been reported to improve cognitive function. Important roles on learning and memory of adenosine and its receptors, such as adenosine A1 and A2A receptors (A1R and A2AR), also have been shown. Therefore, we assume that the improvement of learning and memory induced by cordycepin is likely related to hippocampal adenosine content and adenosine receptor density. Here we investigated the effects of cordycepin on the short-term spatial memory by using a spontaneous alternation behavior (SAB) test in Y-maze, and then examined hippocampal adenosine content and A1R and A2AR densities. We found that orally administrated cordycepin (at dosages of 5 and 10mg/kg twice daily for three weeks) significantly increased the percent of relative alternation of mice in SAB but not altered body weight, hippocampus weight and hippocampal adenosine content. Furthermore, cordycepin decreased A2AR density in hippocampal subareas; however, cordycepin only reduced the A1R density in DG but not CA1 or CA3 region. Our results suggest that cordycepin exerts a nootropic role possibly through modulating A2AR density of hippocampus, which further support the concept that it is mostly A2AR rather than A1R to control the adaptive processes of memory performance. These findings would be helpful to provide a new window into the pharmacological properties of cordycepin for cognitive promotion.

Nootropic and Neuroprotective Effects of Dichrocephala integrifolia on Scopolamine Mouse Model of Alzheimer's Disease.

Alzheimer’s disease the most common form of dementia in the elderly is a neurodegenerative disease that affects 44 millions of people worldwide. The first treatments against Alzheimer’s disease are acetylcholinesterase inhibitors; however, these medications are associated with many side effects. Dichrocephala integrifolia is a traditional herb widely used by indigenous population of Cameroon to treat and prevent Alzheimer’s disease and for memory improvement. In this study, we evaluated the effect of the decoction prepared from leaves of D. integrifolia, on scopolamine-induced memory impairment in mice. Seven groups of six animals were used. The first two groups received distilled water for the distilled water and scopolamine groups. The four test groups received one of the four doses of the decoction of the plant (35, 87.5, 175 or 350 mg/kg p.o.) and the positive control group received tacrine (10 mg/kg), a cholinesterase inhibitor used in the treatment of Alzheimer’s disease, during 10 consecutive days. Scopolamine (1 mg/kg), a cholinergic receptor blocker, administered 30 min after treatments, was used to induce memory impairment to all groups except the distilled water group on day 10 of drug treatment. The behavioral paradigms used to evaluate the effects of the treatment were the elevated plus maze for learning and memory, Y maze for spatial short-term memory, the novel object recognition for recognition memory and Morris water maze for the evaluation of spatial long-term memory. After behavioral tests, animals were sacrificed and brains of a subset were used for the assessment of some biomarkers of oxidative stress (malondialdehyde and reduced glutathione levels) and for the evaluation of the acetylcholinesterase activity. From the remaining subset brains, histopathological analysis was performed. The results of this study showed that, D. integrifolia at the doses of 87.5 and 350 mg/kg significantly (p < 0.01) improved spatial short-term and long-term memory, by increasing the percentage of spontaneous alternation in the Y maze and reducing the escape latency in the Morris water maze. Furthermore, the results of histopathological evaluation showed that D. integrifolia attenuated the neuronal death in the hippocampus induced by scopolamine. The main finding of this work is that D. integrifolia improves learning capacities and counteracts the memory impairment induced by scopolamine. Thus, D. integrifolia can be a promising plant resource for the management of Alzheimer’s disease and memory loss.

Lead exposure in late adolescence through adulthood impairs short-term spatial memory and the neuronal differentiation of adult-born cells in C57BL/6 male mice.

Lead is a neurotoxicant of immense public health importance. Epidemiology studies suggest that heavy metal exposure may be associated with an increased risk of cognitive decline, yet few studies to date have assessed the effect of adult lead exposure on cognitive behavior in animal models. Here, we exposed 6-week-old male C57BL/6 mice to 0.2% lead acetate via drinking water for 12 weeks starting at 6 weeks of age and then assessed for deficits in hippocampus-dependent spatial memory and impairment of adult hippocampal neurogenesis. Lead did not cause locomotor deficits or anxiety in the open field test. However, we found that adult, subchronic lead exposure was sufficient to cause deficits in spatial short-term memory and these deficits persisted through at least 2 months post-lead exposure. Furthermore, we observed that lead-treated mice had fewer adult-born, mature neurons in the dentate gyrus of the hippocampus compared to control animals, suggesting that lead exposure during adolescence and adulthood may impair the neuronal differentiation of adult-born cells. These data suggest that adult lead exposure is sufficient to cause persistent deficits in spatial short-term memory and impair key processes in adult hippocampal neurogenesis.

Neuropeptide S overcomes short term memory deficit induced by sleep restriction by increasing prefrontal cortex activity

Sleep restriction (SR) impairs short term memory (STM) that might be related to different processes. Neuropeptide S (NPS), an endogenous neuropeptide that improves short term memory, activates arousal and decreases anxiety is likely to counteract the SR-induced impairment of STM. The objective of the present study was to find common cerebral pathways in sleep restriction and NPS action in order to ultimately antagonize SR effect on memory.The STM was assessed using a spontaneous spatial alternation task in a T-maze. C57-Bl/6J male mice were distributed in 4 groups according to treatment (0.1nmol of NPS or vehicle intracerebroventricular injection) and to 20h-SR. Immediately after behavioural testing, regional c-fos immunohistochemistry was performed and used as a neural activation marker for spatial short term memory (prefrontal cortex, dorsal hippocampus) and emotional reactivity (basolateral amygdala and ventral hippocampus). Anxiety-like behaviour was assessed using elevated-plus maze task.Results showed that SR impaired short term memory performance and decreased neuronal activation in cingular cortex.NPS injection overcame SR-induced STM deficits and increased neuronal activation in infralimbic cortex. SR spared anxiety-like behavior in the elevated-plus maze. Neural activation in basolateral nucleus of amygdala and ventral hippocampus were not changed after SR.In conclusion, the present study shows that NPS overcomes SR-induced STM deficits by increasing prefrontal cortex activation independently of anxiety-like behaviour.

Comparison of Neuropsychological Functioning Between Adults With Early- and Late-Onset DSM-5 ADHD

Objective: We aimed to compare the visually dependent neuropsychological functioning among adults with Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD who recalled symptom onset by and after age 7 and non-ADHD controls. Method: We divided the participants, aged 17 to 40 years, into three groups—(a) ADHD, onset <7 years (early-onset, n = 142); (b) ADHD, onset between 7 and <12 years (late-onset, n = 41); (c) non-ADHD controls (n = 148)—and compared their neuropsychological functioning, measured by the Cambridge Neuropsychological Testing Automated Battery. Results: Both ADHD groups had deficits in attention and signal detectability, spatial working memory, and short-term spatial memory, but only the early-onset group showed deficits in alertness, set-shifting, and planning after controlling for age, sex, and psychiatric comorbidities. There was no statistical difference between the two ADHD groups in neuropsychological functioning. Conclusion: DSM-5 criteria for diagnosing adult ADHD are not too lax regarding neuropsychological functioning.

Inhibition of p75 neurotrophin receptor does not rescue cognitive impairment in adulthood after isoflurane exposure in neonatal mice

BackgroundIsoflurane is widely used for anaesthesia in humans. Isoflurane exposure of rodents prior to post-natal day 7 (PND7) leads to widespread neurodegeneration in laboratory animals. Previous data from our laboratory suggest an attenuation of apoptosis with the p75 neurotrophin receptor (p75NTR) inhibitor TAT-Pep5. We hypothesized that isoflurane toxicity leads to behavioural and cognitive abnormalities and can be rescued with pre-anaesthesia administration of TAT-Pep5. MethodsNeonatal mouse pups were pretreated with either TAT-Pep5 (25 μl, 10 μM i.p.) or a scrambled control peptide (TAT-ctrl; 25 μl, 10 μM i.p.) prior to isoflurane exposure (1.4%; 4 h) or control (n = 15–26/group). Three to 5 months after exposure, behavioural testing and endpoint assays [brain volume (stereology) and immunoblotting] were performed. ResultsNo significant difference was observed in open field, T-maze, balance beam or wire-hanging testing. The Barnes maze revealed a significant effect of isoflurane (P = 0.019) in errors to find the escape tunnel during the day 5 probe trial, a finding indicative of impaired short-term spatial memory. No difference was found for brain volumes or protein expression. TAT-Pep5 treatment did not reverse the effects of isoflurane on neurocognitive behaviour. ConclusionA single isoflurane exposure to early post-natal mice caused a hippocampal-dependent memory deficit that was not prevented by pre-administration of TAT-Pep5, although TAT-Pep5, an inhibitor of p75NTR, has been shown to reduce isoflurane-induced apoptosis. These findings suggest that neuronal apoptosis is not requisite for the development of cognitive deficits in the adults attendant with neonatal anaesthetic exposure.

Effects of curcumin on short-term spatial and recognition memory, adult neurogenesis and neuroinflammation in a streptozotocin-induced rat model of dementia of Alzheimer’s type

Curcumin is a natural polyphenol with evidence of antioxidant, anti-inflammatory and neuroprotective properties. Recent evidence also suggests that curcumin increases cognitive performance in animal models of dementia, and this effect would be related to its capacity to enhance adult neurogenesis. The aim of this study was to test the hypothesis that curcumin treatment would be able to preserve cognition by increasing neurogenesis and decreasing neuroinflammation in the model of dementia of Alzheimer’s type induced by an intracerebroventricular injection of streptozotocin (ICV-STZ) in Wistar rats. The animals were injected with ICV–STZ or vehicle and curcumin treatments (25, 50 and 100mg/kg, gavage) were performed for 30days. Four weeks after surgery, STZ-lesioned animals exhibited impairments in short-term spatial memory (Object Location Test (OLT) and Y maze) and short-term recognition memory (Object Recognition Test – ORT), decreased cell proliferation and immature neurons (Ki-67- and doublecortin-positive cells, respectively) in the subventricular zone (SVZ) and dentate gyrus (DG) of hippocampus, and increased immunoreactivity for the glial markers GFAP and Iba-1 (neuroinflammation). Curcumin treatment in the doses of 50 and 100mg/kg prevented the deficits in recognition memory in the ORT, but not in spatial memory in the OLT and Y maze. Curcumin treatment exerted only slight improvements in neuroinflammation, resulting in no improvements in hippocampal and subventricular neurogenesis. These results suggest a positive effect of curcumin in object recognition memory which was not related to hippocampal neurogenesis.

Decrease in endogenous brain allopregnanolone induces autism spectrum disorder (ASD)-like behavior in mice: A novel animal model of ASD

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with core symptoms of social impairments and restrictive repetitive behaviors. Recent evidence has implicated a dysfunction in the GABAergic system in the pathophysiology of ASD. We investigated the role of endogenous allopregnanolone (ALLO), a neurosteroidal positive allosteric modulator of GABAA receptors, in the regulation of ASD-like behavior in male mice using SKF105111 (SKF), an inhibitor of type I and type II 5α-reductase, a rate-limiting enzyme of ALLO biosynthesis. SKF impaired sociability-related performance, as analyzed by three different tests; i.e., the 3-chamber test and social interaction in the open field and resident-intruder tests, without affecting olfactory function elucidated by the buried food test. SKF also induced repetitive grooming behavior without affecting anxiety-like behavior. SKF had no effect on short-term spatial working memory or long-term fear memory, but enhanced latent learning ability in male mice. SKF-induced ASD-like behavior in male mice was abolished by the systemic administration of ALLO (1mg/kg, i.p.) and methylphenidate (MPH: 2.5mg/kg, i.p.), a dopamine transporter inhibitor. The effects of SKF on brain ALLO contents in male mice were reversed by ALLO, but not MPH. On the other hand, SKF failed to induce ASD-like behavior or a decline in brain ALLO contents in female mice. These results suggest that ALLO regulates episodes of ASD-like behavior by positively modulating the function of GABAA receptors linked to the dopaminergic system. Moreover, a sex-dependently induced decrease in brain ALLO contents may provide an animal model to study the main features of ASD.

Consequences of Adolescent Exposure to the Cannabinoid Receptor Agonist WIN55,212-2 on Working Memory in Female Rats.

Marijuana is a prevalent illicit substance used by adolescents, and several studies have indicated that adolescent use can lead to long-term cognitive deficits including problems with attention and memory. However, preclinical animal studies that observe cognitive deficits after cannabinoid exposure during adolescence utilize experimenter administration of doses of cannabinoids that may exceed what an organism would choose to take, suggesting that contingency and dose are critical factors that need to be addressed in translational models of consequences of cannabinoid exposure. Indeed, we recently developed an adolescent cannabinoid self-administration paradigm in male rats, and found that prior adolescent self-administration of the cannabinoid receptor agonist WIN55,212-2 (WIN) resulted in improved working memory performance in adulthood. In addition, the doses self-administered were not as high as those that are found to produce memory deficits. However, given known sex differences in both drug self-administration and learning and memory processes, it is possible that cannabinoid self-administration could have different cognitive consequences in females. Therefore, we aimed to explore the effects of self-administered vs. experimenter-administered WIN in adolescent female rats on adult cognitive function. Female rats were trained to self-administer WIN daily throughout adolescence (postnatal day 34–59). A control group self-administered vehicle solution. The acute effects of adolescent WIN self-administration on memory were determined using a short-term spatial memory test 24 h after final SA session; and the long-term effects on cognitive performance were assessed during protracted abstinence in adulthood using a delayed-match-to-sample working memory task. In a separate experiment, females were given daily intraperitoneal (IP) injections of a low or high dose of WIN, corresponding to self-administered and typical experimenter-administered doses, respectively, or its vehicle during adolescence and working memory was assessed under drug-free conditions in adulthood. While self-administration of WIN in adolescence had no significant effects on short-term spatial memory or adult working memory, experimenter administration of WIN resulted in improved adult working memory performance that was more pronounced in the low dose group. Thus, low-dose adolescent WIN exposure, whether self-administered or experimenter-administered, results in either improvements or no change in adult working memory performance in female rats, similar to previous results found in males.

Interaction of reelin and stress on immobility in the forced swim test but not dopamine-mediated locomotor hyperactivity or prepulse inhibition disruption: Relevance to psychotic and mood disorders

RationalePsychotic disorders, such as schizophrenia, as well as some mood disorders, such as bipolar disorder, have been suggested to share common biological risk factors. One such factor is reelin, a large extracellular matrix glycoprotein that regulates neuronal migration during development as well as numerous activity-dependent processes in the adult brain. The current study sought to evaluate whether a history of stress exposure interacts with endogenous reelin levels to modify behavioural endophenotypes of relevance to psychotic and mood disorders. MethodsHeterozygous Reeler Mice (HRM) and wildtype (WT) controls were treated with 50mg/L of corticosterone (CORT) in their drinking water from 6 to 9weeks of age, before undergoing behavioural testing in adulthood. We assessed methamphetamine-induced locomotor hyperactivity, prepulse inhibition (PPI) of acoustic startle, short-term spatial memory in the Y-maze, and depression-like behaviour in the Forced-Swim Test (FST). ResultsHRM genotype or CORT treatment did not affect methamphetamine-induced locomotor hyperactivity, a model of psychosis-like behaviour. At baseline, HRM showed decreased PPI at the commonly used 100msec interstimulus interval (ISI), but not at the 30msec ISI or following challenge with apomorphine. A history of CORT exposure potentiated immobility in the FST amongst HRM, but not WT mice. In the Y-maze, chronic CORT treatment decreased novel arm preference amongst HRM, reflecting reduced short-term spatial memory. ConclusionThese data confirm a significant role of endogenous reelin levels on stress-related behaviour, supporting a possible role in both bipolar disorder and schizophrenia. However, an interaction of reelin deficiency with dopaminergic regulation of psychosis-like behaviour remains unclear.

Decrease in Adult Neurogenesis and Neuroinflammation Are Involved in Spatial Memory Impairment in the Streptozotocin-Induced Model of Sporadic Alzheimer's Disease in Rats.

Early impairments in cerebral glucose metabolism and insulin signaling pathways may participate in the pathogenesis of the sporadic form of Alzheimer's disease (sAD). Intracerebroventricular (ICV) injections of low doses of streptozotocin (STZ) are used to mimic sAD and study these alterations in rodents. Streptozotocin causes impairments in insulin signaling and has been reported to trigger several alterations in the brain, such as oxidative stress, neuroinflammation, and dysfunctions in adult neurogenesis, which may be involved in cognitive decline and are features of human AD. The aim of the present study was to assess the influence of neuroinflammation on the process of adult neurogenesis and consequent cognitive deficits in the STZ-ICV model of sAD in Wistar rats. Streptozotocin caused an acute and persistent neuroinflammatory response, reflected by reactive microgliosis and astrogliosis in periventricular areas and the dorsal hippocampus, accompanied by a marked reduction of the proliferation of neural stem cells in the dentate gyrus of the hippocampus and subventricular zone. Streptozotocin also reduced the survival, differentiation, and maturation of newborn neurons, resulting in impairments in short-term and long-term spatial memory. These results support the hypothesis that neuroinflammation has a detrimental effect on neurogenesis, and both neuroinflammation and impairments in neurogenesis contribute to cognitive deficits in the STZ-ICV model of sAD.

Elevated paternal glucocorticoid exposure modifies memory retention in female offspring

Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans.

0044 DIFFERENTIAL EFFECTS OF PARADOXICAL SLEEP DEPRIVATION ON ADOLESCENT AND ADULT MICE

Sleep insufficiency has become a serious health issue. In the modern society, most of the people, including the adolescence, do not obtain enough sleep. Since adolescence is a critical period for brain development, the consequences of insufficient sleep during adolescence should be concerned. The current study emphasized the effects of 72-hour paradoxical sleep deprivation (SD) on behavioral and morphological aspects in adolescent mice and used adult mice for comparison. In this study, we examined the acute effects of 72-hour paradoxical SD. 5 weeks old and 10–12 weeks old male C57/BL6 mice were used. The two time points were chosen to represent the periods of adolescence and adulthood, respectively. SD for 72 hours were conducted using modified multiple platform method. For mice kept in the home cage and on big platforms, sleep time was not limited and used as controls. Mice of SD and control groups were examined in behavioral, neurochemical and histological aspects. Our results showed that the short-term spatial memory, examined by Y-maze spontaneous alternation test, was affected by 72-hour paradoxical SD in adolescent mice but not in adult mice. The complexity of granule cells in dentate gyrus (DG) was reduced after SD in adolescent but minimal changes were observed in adult animals. There was an increase of spine density in DG granule cell after 72-hour paradoxical SD in adolescent and not in adult SD animals. Hippocampal neurogenesis in the DG was reduced by SD in both adolescent and adult groups. Results from this study revealed that SD negatively impacted the cognitive function by impairing the spatial working memory in adolescent but not in adult mice. Moreover, the analyses of dendritic complexity and spine density of granule cells in the hippocampal DG also indicated age-related morphological alterations after 72-hour sleep deprivation. Our results indicated the adolescent mice are relatively more sensitive to SD than the adult mice. It is the first study, to our knowledge, that compared the differential effects of SD on adolescent and adult mice. None.

Attentional capture by deviant sounds: A noncontingent form of auditory distraction?

The occurrence of an unexpected, infrequent sound in an otherwise homogeneous auditory background tends to disrupt the ongoing cognitive task. This "deviation effect" is typically explained in terms of attentional capture whereby the deviant sound draws attention away from the focal activity, regardless of the nature of this activity. Yet, there is theoretical and empirical evidence suggesting that the attention-capture mechanism underlying this form of distraction could rather be triggered in a task-contingent fashion. The present study aimed at determining whether the auditory deviation effect reflects the action of either a stimulus-driven or a task-contingent orienting mechanism. To do so, we conducted a systematic investigation whereby the impact of verbal deviants-a letter embedded in the repetition of another letter-and spatial deviants-a sound presented contralaterally to the other sounds-on verbal and spatial short-term memory (STM) was assessed. This study established that both verbal and spatial deviants can hinder both verbal and spatial order-reconstruction (Experiment 1) and missing-item tasks (Experiment 2). Such results demonstrate that the deviation effect reflects a general form of auditory distraction as interference took place both within and across domains and regardless of the processes engaged in the focal task. (PsycINFO Database Record

SA97. Elevated GPR85 Expression in Rat Hippocampus Impairs Spatial Short-Term Memory by an Unknown Molecular Mechanism

SA97. Elevated GPR85 Expression in Rat Hippocampus Impairs Spatial Short-Term Memory by an Unknown Molecular Mechanism

Informative Cues Facilitate Saccadic Localization in Blindsight Monkeys.

Patients with damage to the primary visual cortex (V1) demonstrate residual visual performance during laboratory tasks despite denying having a conscious percept. The mechanisms behind such performance, often called blindsight, are not fully understood, but the use of surgically-induced unilateral V1 lesions in macaque monkeys provides a useful animal model for exploring such mechanisms. For example, V1-lesioned monkeys localize stimuli in a forced-choice condition while at the same time failing to report awareness of identical stimuli in a yes-no detection condition, similar to human patients. Moreover, residual cognitive processes, including saliency-guided eye movements, bottom-up attention with peripheral non-informative cues, and spatial short-term memory, have all been demonstrated in these animals. Here we examined whether post-lesion residual visuomotor processing can be modulated by top-down task knowledge. We tested two V1-lesioned monkeys with a visually guided saccade task in which we provided an informative foveal pre-cue about upcoming target location. Our monkeys fixated while we presented a leftward or rightward arrow (serving as a pre-cue) superimposed on the fixation point (FP). After various cue-target onset asynchronies (CTOAs), a saccadic target (of variable contrast across trials) was presented either in the affected (contra-lesional) or seeing (ipsi-lesional) hemifield. Critically, target location was in the same hemifield that the arrow pre-cue pointed towards in 80% of the trials (valid-cue trials), making the cue highly useful for task performance. In both monkeys, correct saccade reaction times were shorter during valid than invalid trials. Moreover, in one monkey, the ratio of correct saccades towards the affected hemifield was higher during valid than invalid trials. We replicated both reaction time and correct ratio effects in the same monkey using a symbolic color cue. These results suggest that V1-lesion monkeys can use informative cues to localize stimuli in the contra-lesional hemifield, consistent with reports of a human blindsight subject being able to direct attention in cueing paradigms. Because the superior colliculus (SC) may contribute to residual visual capabilities after V1 lesions, and because this structure is important for controlling attentional resources, we hypothesize that our results reflect, among others, SC involvement in integrating top-down task knowledge for guiding orienting behavior.

Fluoride and arsenic exposure affects spatial memory and activates the ERK/CREB signaling pathway in offspring rats

Fluoride and arsenic are inorganic contaminants that occur in the natural environment. Chronic fluoride and/or arsenic exposure can induce developmental neurotoxicity and negatively influence intelligence in children, although the underlying molecular mechanisms are poorly understood. This study explored the effects of fluoride and arsenic exposure in drinking water on spatial learning, memory and key protein expression in the ERK/CREB signaling pathway in hippocampal and cerebral cortex tissue in rat offspring. Pregnant rats were divided into four groups. Control rats drank tap water, while rats in the three exposure groups drank water with sodium fluoride (100mg/L), sodium arsenite (75mg/L), and a sodium fluoride (100mg/L) and sodium arsenite (75mg/L) combination during gestation and lactation. After weaning, rat pups drank the same solution as their mothers. Spatial learning and memory ability of pups at postnatal day 21 (PND21) and postnatal day 42 (PND42) were measured using a Morris water maze. ERK, phospho-ERK (p-ERK), CREB and phospho-CREB (p-CREB) protein expression in the hippocampus and cerebral cortex was detected using Western blot. Compared with the control pups, escape latencies increased in PND42 pups exposed to arsenic and co-exposed to fluoride and arsenic, and the short-term and long-term spatial memory ability declined in pups exposed to fluoride and arsenic, both alone and in combination. Compared with controls, ERK and p-ERK levels decreased in the hippocampus and cerebral cortex in pups exposed to combined fluoride and arsenic. CREB protein expression in the cerebral cortex decreased in pups exposed to fluoride, arsenic, and the fluoride and arsenic combination. p-CREB protein expression in both the hippocampus and cerebral cortex was decreased in pups exposed to fluoride and arsenic in combination compared to the control group. There were negative correlation between the proteins expression and escape latency periods in pups. These data indicate that exposure to fluoride and arsenic in early life stage changes ERK, p-ERK, CREB and p-CREB protein expression in the hippocampus and cerebral cortex of rat offspring at PND21 and PND 42, which may contribute to impaired neurodevelopment following exposure.

Loganin enhances long-term potentiation and recovers scopolamine-induced learning and memory impairments

Although the incidence rate of dementia is rapidly growing in the aged population, therapeutic and preventive reagents are still suboptimal. Various model systems are used for the development of such reagents in which scopolamine is one of the favorable pharmacological tools widely applied.Loganin is a major iridoid glycoside obtained from Corni fructus (Cornusofficinalis et Zucc) and demonstrated to have anti-inflammatory, anti-tumor and osteoporosis prevention effects. It has also been found to attenuate Aβ-induced inflammatory reactions and ameliorate memory deficits induced by scopolamine. However, there has been limited information available on how loganin affects learning and memory both electrophysiologically and behaviorally.To assess its effect on learning and memory, we investigated the influence of acute loganin administration on long-term potentiation (LTP) using organotypic cultured hippocampal tissues. In addition, we measured the effects of loganin on the behavior performance related to avoidance memory, short-term spatial navigation memory and long-term spatial learning and memory in the passive avoidance, Y-maze, and Morris water maze learning paradigms, respectively.Loganin dose-dependently increased the total activity of fEPSP after high frequency stimulation and attenuated scopolamine-induced blockade of fEPSP in the hippocampal CA1 area. In accordance with these findings, loganin behaviorally attenuated scopolamine-induced shortening of step-through latency in the passive avoidance test, reduced the percent alternation in the Y-maze, and increased memory retention in the Morris water maze test.These results indicate that loganin can effectively block cholinergic muscarinic receptor blockade -induced deterioration of LTP and memory related behavioral performance. Based on these findings, loganin may aid in the prevention and treatment of Alzheimer's disease and learning and memory-deficit disorders in the future.