Memory Performance In Mice Research Articles

Evaluation of neurotoxicity and hepatotoxicity effects of acute and sub-acute oral administration of unripe ackee (Blighia sapida) fruit extract.

Ackee (Blighia sapida) is a commonly eaten fruit that is indigenous to West Africa and Jamaica. Ackee poisoning in young children have been reported in parts of Nigeria due to consumption of the unripe fruits. This study was designed to identify potential mechanisms of acute and sub-acute toxicity of unripe B. sapida fruit extract (BSE). Acute toxic effect was investigated in mice of either sex administered BSE 2000 mg/kg. The sub-acute toxicity effects were investigated in mice of either sex that received 28 days repeated administration of BSE (100 and 500 mg/kg, p.o.). Locomotor activity and memory performance were measured as well as seizure vulnerability in PTZ-induced model. Liver enzymes were assessed in the serum. Acetylcholinesterase, oxidative stress parameters and histopathological changes were assessed in the brain and liver tissues. Signs and symptoms of toxicity such as urination, tremor, depressed locomotion and death were observed in acute toxicity test. Sub-acute dosing caused significant impairment in locomotor activity and memory performance in mice. Seizure threshold was shortened in BSE-treated compared to control mice. Brain acetylcholinesterase activity was significantly increased. Alkaline phosphatase (ALP) was significantly elevated in mice that received BSE (500 mg/kg). Furthermore, BSE caused significant increase in oxidative stress expressed in nitrite, malondialdehyde, reduced glutathione and catalase in the brain and liver tissues. Histological staining revealed neuronal damage of brain hippocampus and hepatocellular swelling and necrosis. Blighia sapida unripe fruit extract increased susceptibility to seizure and impaired locomotor and memory function. The biochemical and histopathological findings revealed potential toxicity mechanisms related to neurotoxicity and hepatotoxicity.

Jobelyn Attenuates Oxidative Stress and Improves Memory Performance in Mice Exposed to Anoxic Stress.

Chronic stress impairs memory by damaging brain cells via induction of oxidative stress. Hence, the use of agents with antioxidant activity is being investigated as potential drugs against chronic stress-induced memory decline. This study evaluated the effect of Jobelyn® (JB), a potent antioxidant food supplement on memory deficit induced by anoxic stress in mice and on brain levels of biomarkers of oxidative stress. Male mice were distributed into 6 groups (n=6): group 1 (non-stress control) and group 2 (stress control) were a given saline, groups 3-5 received JB (5, 10, 25 and 50 mg/kg) while group 6 had donepezil-DP (1 mg/kg). Thirty minutes later, mice in groups 2-5 were exposed twice to anoxic condition for 15 min in acute anoxic stress. However, in sub-chronic anoxic stress, mice in groups 2-6 were subjected to the same anoxic condition for 15 min twice daily for 5 consecutive days. Thereafter, memory performance was assessed in each case using Y-maze paradigm. The concentrations of biomarkers of oxidative stress (glutathione and malondialdehyde) were only determined in the brains of mice exposed to sub-chronic anoxic stress. Mice exposed to sub-chronic anoxic stress had impaired memory function, which was significantly attenuated by JB. The increased oxidative stress as shown by elevated levels of malondialdehyde and decreased concentrations of glutathione was also reduced by JB. The results of this study suggest that the antioxidant activity of Jobelyn® might be contributing to its ability to attenuate sub-chronic anoxic stress-induced memory deficits in mice.

Glutamate transporter GLT1 inhibitor dihydrokainic acid impairs novel object recognition memory performance in mice

Glutamate transporter GLT1 mediates glutamate uptake, and maintains glutamate homeostasis in the synaptic cleft. Previous studies suggest that blockade of glutamate uptake affects synaptic transmission and plasticity. However, the effect of GLT1 blockade on learning and memory still receives little attention. In the present study, we examined the effect of unilateral intracerebroventricular injection of dihydrokainic acid (DHK), a GLT-1 inhibitor, on novel object recognition (NOR) memory performance. The NOR task involved three sessions including habituation, sampling and test. In experiment 1, DHK injection 0.5 h pre-sampling impaired short-term NOR memory performance. In experiment 2, DHK injection 0.5 h pre-sampling impaired long-term NOR memory acquisition. In experiment 3, DHK injection immediately but not 6 h post-sampling impaired long-term NOR memory consolidation. In experiment 4, DHK injection 0.5 h pre-test impaired long-term NOR memory retrieval. Furthermore, DHK-induced memory performance impairment was not due to its effects on nonspecific responses such as locomotor activity and exploratory behavior. The current findings further extend previous studies on the effects of disruption of glutamate homeostasis on learning and memory.

The hypothalamus as the primary brain region of metabolic abnormalities in APP/PS1 transgenic mouse model of Alzheimer's disease

Alzheimer's disease (AD) is an amyloid-related neurodegenerative disorder and is also considered to be a metabolic disease. Thus, investigation of metabolic mechanisms of amyloid pathology progression is of substantial importance for the diagnosis, prevention and treatment of AD. In the present study, cognitive function and brain metabolism were explored in the transgenic APP/PS1 mouse model of amyloid pathology at different ages. Using an NMR-based metabolomic approach, we examined metabolic changes in six different brain regions of wild-type and APP/PS1 mice at 1, 5 and 10months of age. Learning and memory performance in mice was evaluated using the Morris water maze test. Furthermore, a generalized linear mixed model was employed to analyze the interaction effect between the mouse-type and brain region (or age) on metabolic alterations. Brain region-specific changes in energy metabolism occurred prior to a very early-stage of amyloid pathology (1month of age) in APP/PS1 mice. A hypermetabolic state was identified in the brains of APP/PS1 mice at 5months of age, and the hypothalamus was identified as the main brain region that underwent significant metabolic alterations. The cognitive function of APP/PS1 mice was impaired at 10months of age; moreover, the hypermetabolic state identified in various brain regions at 5months of age was also significantly decreased. In conclusion, our results suggest that a hypothalamic metabolism abnormality may comprise a potential indicator for the early-diagnosis and monitoring of amyloid pathology progression.

Effects of Rat Anti-mouse Interleukin-6 Receptor Antibody on the Recovery of Cognitive Function in Stroke Mice.

This study aimed to investigate the effects of rat anti-mouse interleukin (IL)-6 receptor antibody (MR16-1) on the recovery of cognitive function in stroke mice. Adult male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO). Mice were randomly assigned into three groups: sham group, model group, and MR16-1 group. After the treatment of MR16-1, spatial learning and memory performance of mice were evaluated by the Morris water maze (MWM) and Y-maze tests. Then, brain slices were obtained and infarct volume and neuronal apoptosis were assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining and Terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay, respectively. Protein expression levels of apoptosis-associated proteins and multiple inflammatory cytokines were determined by Western blot analysis. Real-time quantitative PCR (RT-PCR) was used to examine the mRNA levels of various inflammatory cytokines in brain slices and cerebrospinal fluid (CSF). The results showed that MR16-1 improved performances of stroke mice in MWM and Y-maze tests. Moreover, MR16-1 ameliorated MCAO-induced infarct, neuronal apoptosis, and inflammatory response. Furthermore, MR16-1 promoted the expression of Bcl-2 and inhibited the expression of Bax in stroke mice, which revealed the inhibitory effect of MR16-1 on neuronal apoptosis. IL-6 levels in brain and CSF were both decreased by MR16-1 treatment in stroke mice. MR16-1 ameliorated cognitive dysfunction and apoptosis in stroke mice, involving the inhibition of inflammatory response and pro-apoptotic Bax, and the up-regulation of anti-apoptotic Bcl-2. The data supported that MR16-1 might be a potential therapeutic drug for the treatment of stroke.

The group II metabotropic glutamate receptor agonist LY354740 and the D2 receptor antagonist haloperidol reduce locomotor hyperactivity but fail to rescue spatial working memory in GluA1 knockout mice.

Group II metabotropic glutamate receptor agonists have been suggested as potential anti‐psychotics, at least in part, based on the observation that the agonist LY354740 appeared to rescue the cognitive deficits caused by non‐competitive N‐methyl‐d‐aspartate receptor (NMDAR) antagonists, including spatial working memory deficits in rodents. Here, we tested the ability of LY354740 to rescue spatial working memory performance in mice that lack the GluA1 subunit of the AMPA glutamate receptor, encoded by Gria1, a gene recently implicated in schizophrenia by genome‐wide association studies. We found that LY354740 failed to rescue the spatial working memory deficit in Gria1 −/− mice during rewarded alternation performance in the T‐maze. In contrast, LY354740 did reduce the locomotor hyperactivity in these animals to a level that was similar to controls. A similar pattern was found with the dopamine receptor antagonist haloperidol, with no amelioration of the spatial working memory deficit in Gria1 −/− mice, even though the same dose of haloperidol reduced their locomotor hyperactivity. These results with LY354740 contrast with the rescue of spatial working memory in models of glutamatergic hypofunction using non‐competitive NMDAR antagonists. Future studies should determine whether group II mGluR agonists can rescue spatial working memory deficits with other NMDAR manipulations, including genetic models and other pharmacological manipulations of NMDAR function.

Modulation of recognition memory performance by light requires both melanopsin and classical photoreceptors.

Acute light exposure exerts various effects on physiology and behaviour. Although the effects of light on brain network activity in humans are well demonstrated, the effects of light on cognitive performance are inconclusive, with the size, as well as direction, of the effect depending on the nature of the task. Similarly, in nocturnal rodents, bright light can either facilitate or disrupt performance depending on the type of task employed. Crucially, it is unclear whether the effects of light on behavioural performance are mediated via the classical image-forming rods and cones or the melanopsin-expressing photosensitive retinal ganglion cells. Here, we investigate the modulatory effects of light on memory performance in mice using the spontaneous object recognition task. Importantly, we examine which photoreceptors are required to mediate the effects of light on memory performance. By using a cross-over design, we show that object recognition memory is disrupted when the test phase is conducted under a bright light (350 lux), regardless of the light level in the sample phase (10 or 350 lux), demonstrating that exposure to a bright light at the time of test, rather than at the time of encoding, impairs performance. Strikingly, the modulatory effect of light on memory performance is completely abolished in both melanopsin-deficient and rodless–coneless mice. Our findings provide direct evidence that melanopsin-driven and rod/cone-driven photoresponses are integrated in order to mediate the effect of light on memory performance.

Exposure to low doses of 137cesium and nicotine during postnatal development modifies anxiety levels, learning, and spatial memory performance in mice

Radiation therapy is a major cause of long-term complications observed in survivors of pediatric brain tumors. However, the effects of low-doses of ionizing radiation (IR) to the brain are less studied. On the other hand, tobacco is one of the most heavily abused drugs in the world. Tobacco is not only a health concern for adults. It has also shown to exert deleterious effects on fetuses, newborns, children and adolescents. Exposure to nicotine (Nic) from smoking may potentiate the toxic effects induced by IR on brain development. In this study, we evaluated in mice the cognitive effects of concomitant exposure to low doses of internal radiation (137Cs) and Nic during neonatal brain development. On postnatal day 10 (PND10), two groups of C57BL/6J mice were subcutaneously exposed to 137-Cesium (137Cs) (4000 and 8000 Bq/kg) and/or Nic (100 μg/ml). At the age of two months, neurobehavior of mice was assessed. Results showed that exposure to IR-alone or in combination with Nic-increased the anxiety-like of the animals without changing the activity levels. Moreover, exposure to IR impaired learning and spatial memory. However, Nic administration was able to reverse this effect, but only at the low dose of 137Cs

New insights into selective PDE4D inhibitors: 3-(Cyclopentyloxy)-4-methoxybenzaldehyde O-(2-(2,6-dimethylmorpholino)-2-oxoethyl) oxime (GEBR-7b) structural development and promising activities to restore memory impairment

Phosphodiesterase type 4D (PDE4D) has been indicated as a promising target for treating neurodegenerative pathologies such as Alzheimer's Disease (AD). By preventing cAMP hydrolysis, PDE4 inhibitors (PDE4Is) increase the cAMP response element-binding protein (CREB) phosphorylation, synaptic plasticity and long-term memory formation. Pharmacological and behavioral studies on our hit GEBR-7b demonstrated that selective PDE4DIs could improve memory without causing emesis and sedation. The hit development led to new molecule series, herein reported, characterized by a catechol structure bonded to five member heterocycles. Molecular modeling studies highlighted the pivotal role of a polar alkyl chain in conferring selective enzyme interaction. Compound 8a showed PDE4D3 selective inhibition and was able to increase intracellular cAMP levels in neuronal cells, as well as in the hippocampus of freely moving rats. Furthermore, 8a was able to readily cross the blood-brain barrier and enhanced memory performance in mice without causing any emetic-like behavior. These data support the view that PDE4D is an adequate molecular target to restore memory deficits in different neuropathologies, including AD, and also indicate compound 8a as a promising candidate for further preclinical development.

Sulfate-reducing bacteria impairs working memory in mice

The ability of gut microbes to bi-directionally communicate with the brain and vice versa form the basis of the gut microbiome-central nervous system axis. It has been shown that inoculation with pathogenic gut bacteria alters the behavior of mice; however, it is not known whether or not non-pathogenic resident microbes have similar effects. In this study, we tested the hypothesis that the administration of sulfate-reducing bacteria (SRB), a specific group of resident gut bacteria that generate hydrogen sulfide (H2S), impair learning and memory performance in mice tested in an 8-arm radial maze and Morris water maze. We found that mice spent more time in the center of the maze when they were gavaged with live SRB as compared to mice given saline (control), lactulose+mannitol (L/M), or killed SRB. SRB-gavaged mice were also tested using the Morris water maze and were found to take longer to complete the test, spend more time further from the platform, and have a longer path length to reach the platform. This effect of SRB on maze performance was associated with a higher concentration of H2S in the small intestine and cecum. We conclude that SRB, a specific resident gut bacterial species, could impair cognitive function in mice.

Inability to acquire spatial information and deploy spatial search strategies in mice with lesions in dorsomedial striatum

Dorsal striatum has been shown to contribute to spatial learning and memory, but the role of striatal subregions in this important aspect of cognitive functioning remains unclear. Moreover, the spatial-cognitive mechanisms that underlie the involvement of these regions in spatial navigation have scarcely been studied. We therefore compared spatial learning and memory performance in mice with lesions in dorsomedial (DMS) and dorsolateral striatum (DLS) using the hidden-platform version of the Morris water maze (MWM) task. Compared to sham-operated controls, animals with DMS damage were impaired during MWM acquisition training. These mice displayed delayed spatial learning, increased thigmotaxis, and increased search distance to the platform, in the absence of major motor dysfunction, working memory defects or changes in anxiety or exploration. They failed to show a preference for the target quadrant during probe trials, which further indicates that spatial reference memory was impaired in these animals. Search strategy analysis moreover demonstrated that DMS-lesioned mice were unable to deploy cognitively advanced spatial search strategies. Conversely, MWM performance was barely affected in animals with lesions in DLS. In conclusion, our results indicate that DMS and DLS display differential functional involvement in spatial learning and memory. Our results show that DMS, but not DLS, is crucial for the ability of mice to acquire spatial information and their subsequent deployment of spatial search strategies. These data clearly identify DMS as a crucial brain structure for spatial learning and memory, which could explain the occurrence of neurocognitive impairments in brain disorders that affect the dorsal striatum.

Long-lasting memory abnormalities following exposure to the mouse defense test battery: An animal model of PTSD

Memory dysfunctions are thought to play a crucial role both in the development and the maintenance of post-traumatic stress disorder (PTSD). Patients suffering from this condition persistently re-experience the traumatic event particularly when exposed to trauma-related cues and they display memory alterations. The objective of the present study was to investigate the long-term effects of a traumatic stress exposure on defensive behaviors and memory performance in mice confronted with a natural threat (i.e. a rat) in the defense test battery (MDTB), a procedure developed by the Blanchard group in the early nineties. The object recognition task, which addresses certain aspects of episodic memory, was used to assess the long-term consequences of stress on memory function. Mice were exposed to the MDTB followed two weeks later by a re-exposure to the test apparatus, but in the absence of the threat stimulus. Two hours after the second exposure to the MDTB apparatus, mice were exposed to the object recognition task (ORT). Another set of animals was used which were either exposed to the first or to the second MDTB session, before being tested in the ORT. Results showed that MDTB exposure produced long-lasting alterations in some defensive behaviors, such as escape attempts from the apparatus, which were increased during the re-exposure session at day 14 compared to non-exposed control mice. While exposure to the MDTB context only did not affect memory performance in the ORT, confrontation with the threat stimulus in the MDTB on day 1 impaired episodic memory two weeks after the stressful event. Finally, mice confronted both with the rat on day 1 and the MDTB context on day 14 displayed intact episodic memory performance in the ORT. We hypothesize that re-exposure to the context following a stressful event resulted in an increase of arousal, which subsequently led to an improvement in cognitive performance, a phenomenon also described in PTSD patients. The MDTB is a typical example of the tremendous efforts of Blanchard's lab to increase the translatability potential of the behavioral models of central nervous system disorders.

Consequences of temporary inhibition of the medial amygdala on social recognition memory performance in mice.

Different lines of investigation suggest that the medial amygdala is causally involved in the processing of information linked to social behavior in rodents. Here we investigated the consequences of temporary inhibition of the medial amygdala by bilateral injections of lidocaine on long-term social recognition memory as tested in the social discrimination task. Lidocaine or control NaCl solution was infused immediately before learning or before retrieval. Our data show that lidocaine infusion immediately before learning did not affect long-term memory retrieval. However, intra-amygdalar lidocaine infusions immediately before choice interfered with correct memory retrieval. Analysis of the aggressive behavior measured simultaneously during all sessions in the social recognition memory task support the impression that the lidocaine dosage used here was effective as it—at least partially—reduced the aggressive behavior shown by the experimental subjects toward the juveniles. Surprisingly, also infusions of NaCl solution blocked recognition memory at both injection time points. The results are interpreted in the context of the importance of the medial amygdala for the processing of non-volatile odors as a major contributor to the olfactory signature for social recognition memory.

Effects of sage extract on memory performance in mice and acetylcholinesterase activity

Salvia officinalis L. (sage) has been widely used in the Tunisian traditional medicine for the treatment of digestive system and memory disorders. This work aims to investigate the anti-amnesiac and antioxidant activity of aqueous extract of S.officinalis (ASOE) in mice. Evaluation of memory functions in rodents was assessed by Y-maze active test after an initial acquisition phase. Results showed that the S.officinalis aqueous extract had high total phenolic contents (6.2mg gallic E/g extract) and flavonoids (2.44mg catechin E/g extract). It exhibited an interesting scavenging activity (IC50=14.5μg/ml). The mice treated with 300mg/kg body weight for 7 days exhibited a significant decrease in avoidance and discrimination errors during a retention trial compared to control group (P<0.05). Acetylcholinesterase (AChE) activity significantly decreased in mice treated with the extract of sage. These findings suggested that aqueous extract of sage leaves possess a mnemonic effect on adult male mice, confirming their use in traditional medicine.

Preventive Effect of Baicalein on Methamphetamine-Induced Amnesia in the Passive Avoidance Test in Mice

Background/Aims: Methamphetamine abuse may produce cognitive impairment. Baicalein, a bioactive flavonoid, has antioxidative, anti-inflammatory and neuroprotective effects. This study examined the effects of baicalein pretreatment on memory performance in the passive avoidance test after either one dose or an acute binge of methamphetamine in Institute of Cancer Research (ICR) mice. Methods: Methamphetamine was administered by intraperitoneal (i.p.) injection of either one dose (3 mg/kg) or an acute binge (3 mg/kg, 4 i.p. injections at 2-hour intervals). The effects of baicalein pretreatment (1 mg/kg, i.p.) on methamphetamine-induced changes of locomotor activity and memory performance were compared with those of eticlopride, a selective dopamine D₂ receptor antagonist. The effects of baicalein on acute binge methamphetamine-induced oxidative stress (malondialdehyde- and nitrotyrosine-modified protein production) in the mouse hippocampus were also examined. Results: One-dose methamphetamine treatment (i.p., 30 min before or immediately after the training trial) induced hyperlocomotion and amnesia in mice, which were blocked by eticlopride but not by baicalein pretreatment. The memory performance in mice was impaired 5 days after acute binge methamphetamine, which was significantly attenuated by baicalein but not by eticlopride pretreatment. Baicalein pretreatment also attenuated acute binge methamphetamine-induced oxidative stress in the mouse hippocampus. Conclusions: Baicalein exhibits antioxidative and neuroprotective effects in attenuating acute binge methamphetamine-induced memory deficits and oxidative hippocampal damage.

Hplc-ESI-MS/MS analysis of the water-soluble extract from Ziziphi spinosae semen and its ameliorating effect of learning and memory performance in mice.

Background:Ziziphi Spinosae Semen (ZSS), the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H. F. Chow., is a traditional herb for insomnia and anxiety in eastern Asia. However, few researches have been concerned with its effect on ameliorating memory and learning performance.Objective:To investigate the constituents of ZSS water soluble extract and its ameliorating learning and memory in mice.Materials and Methods:A new high performance liquid chromatography coupled with tandem mass spectrometry (HPLC-ESI-MS/MS) method was developed and validated to determine the main constituents in the extract. The effect of ZSS water soluble extract on memory and learning performance was investigated in mice by Y-maze and passive avoidance test.Results:The extract could significantly decrease the number of errors (NOE), and increase the transfer latency time (TLT) and electrical stimuli time (EST). In addition, spinosin, jujuboside A (JuA) and jujuboside B (JuB) were simultaneously identified and quantified in the extract. Their contents in the extract were as followed: Spinosin (223.51mg/g), JuA (63.76mg/g) and JuB (26.29mg/g).Conclusion:The extract played a promising role in ameliorating memory in mice with alcohol induced memory retrieval disorders, and might help to improve learning capacity to some extent. Spinosin, JuA and JuB were the predominant constituents, which might be mainly responsible for the definite activity.

Ghrelin increases hippocampal recombination activating gene 1 expression and spatial memory performance in mice

Ghrelin, which has been shown to improve memory retention, is an endogenous ligand for the growth hormone secretagogue receptor. Recombination activating gene 1 (Rag1), which plays a critical role in the development and maturation of lymphocytes in the immune system, is also expressed in the central nervous system, particularly in the hippocampus, and has been implicated in memory formation. In the current study, the effects of ghrelin on Rag1 expression in the hippocampus and spatial memory performance in wild-type and Rag1 knockout (KO) mice were examined. The Morris water maze test was used to compare the spatial memory performance of wild-type and Rag1-KO mice. Transmission electron microscopy was used to assess morphological changes in synaptic shape and numbers in hippocampal areas after peripheral administration of ghrelin to wild-type and Rag1-KO mice. In wild-type mice, ghrelin increased synaptic vesicles and postsynaptic membrane deposits in the hippocampal CA3 region, shortened water maze escape latencies, and increased platform spans. In Rag1-KO mice, the escape latencies were significantly increased compared with the group of normal mice. Compared with wild-type mice, Rag1-KO mice showed decreasing platform spans. A tendency toward a shortening of the escape latency times and an increase in the platform spans in Rag1-KO mice was observed after ghrelin injection, but this difference was not statistically significant compared with control mice. After the administration of ghrelin, the expression of Rag1 in the hippocampus was significantly increased compared with control mice. Our results suggest that ghrelin potentiates learning and memory in mice, which may be, at least partly, through the regulation of hippocampal Rag1.

Modulation of 5-HT7 receptor: effect on object recognition performances in mice

Recent data suggest that 5-HT7 receptors (5-HT7R) are involved in memory processes and, particularly, those related to novelty-induced arousal, even though this remains so far speculative and controversial. In order to assess the role of 5-HT7R in episodic-like memory, mice were administered 5-carboxamidotryptamine (5-CT, a 5-HT1A/1B/1D/7R agonist) and/or SB-269970 (a selective 5-HT7R antagonist) immediately after the acquisition session of the novel object recognition test. The object recognition test was performed in order to assess the effects of modulation of 5-HT7R during consolidation phase on episodic-like memory performances in mice. A protocol including 3 days of familiarisation to the apparatus has been realised in order to decrease the effect of novelty-induced arousal. With a 2-h delay, SB-269970 (3 and 10 mg/kg, administered subcutaneously) impaired the discrimination of the novel object. With a 4-h delay, while control mice were not able to discriminate the novel object, mice treated with 5-CT (1 mg/kg) showed a significant discrimination. This promnesic effect with a long delay is effectively mediated by 5-HT7R activation since it was blocked by SB-269970 (10 mg/kg), but not by WAY-100135 (10 mg/kg) or by GR-127935 (10 mg/kg). These data suggest that 5-HT7R tonically modulates cognitive processes involved in consolidation performances in object recognition. Therefore, 5-HT7R could be a promising target to treat memory dysfunctions (especially episodically related deficits) related to normal or pathological ageing.

Overexpressing human wild- LRRK2 increases spatial recognition and working memory performance in mice

Overexpressing human wild- LRRK2 increases spatial recognition and working memory performance in mice

Optimization of apparatus design and behavioral measures for the assessment of visuo-spatial learning and memory of mice on the Barnes maze

We have previously shown that apparatus design can affect visual-spatial cue use and memory performance of mice on the Barnes maze. The present experiment extends these findings by determining the optimal behavioral measures and test procedure for analyzing visuo-spatial learning and memory in three different Barnes maze designs. Male and female C57BL/6J mice were trained with a stable or random escape hole location and the sensitivities (statistical power) of four commonly used measures of learning and three measures of memory to detect differences between these training procedures were compared on each maze design. A maze design with a large diameter and no wall was optimal, because mice showed a reliable use of extra-maze visual cues, visuo-spatial search strategies, and spatial memory. A maze design with a small diameter, surrounding wall, and intra-maze visual cues was the least sensitive for determining visuo-spatial learning and memory, because mice showed little evidence of extra-maze cue use. Errors, distance traveled, and hole deviation scores were more sensitive measures of learning than latency to find the escape hole. Measures based on locating the escape hole (primary measures) were more sensitive than measures based on entering the escape hole (total measures). Measures of memory had similar levels of sensitivity on each maze. This experiment demonstrates that both apparatus design and the behavioral measures used as indicators of learning and memory can influence the ability of the Barnes maze to detect visuo-spatial learning and memory impairments in mice.