Spatial Learning Performance Research Articles

5-Phenyl-1, 2, 4-Triazole- 3- Thiol subchronic exposure induce neuro-comportemental desorder in Wistar rats

Triazole and its derivatives possess a great importance in medicinal chemis-try with different biological effects; antiviral, antifungical, antibacterial and analgesic. The purpose of the present work is to assess the effects of 5 phe-nyl 1,2,4 Traizole 3 thiol (5 PTT) through a neurobehavioral exploration in Wistar rats. 5 PTT exposured rats showed increased body weight and brain weight. The open field test revealed a significant decrease in the number of crossed squares. However, the results related to the forced swimming test present a significant rise in the immobility time compared to the vehicle group. Furthermore, the Y maze test show that exposure to 5 PTT is associated with impairment of spatial learning performance and memory deficit is explained by a significant increase of the percentage of spontaneous alterna-tion in the exposed animals, the plus maze test revealed that 5 PTT admin-istrations reduced significantly the open arms time. Histological brain analy-sis show an alteration of tissue architecture and perivascular palisade in treated rats compared to vehicle rats. Our study demonstrated that 5 PTT exposures can cause neurotoxic effects that disrupt spatial learning and memory performance and induce a depressive state which reflects an altera-tion of the neurodevelopment process.

Pimpinella anisum essentiel oil enhances spatial learning performance of rats exposed to Hgcl2 during the developmental period

The essential oil of Pimpinella anisum has been widely used in traditional medicine to treat a variety of diseases. This study was aimed to test, in vivo, effect of exposition to mercury chloride (100mg/L) in wistar rats during the gestation and lactation period. On the other hand, treatment of pups with essential oil of P. anisum (0.25 ml/kg) for 21 days. The behavioural patterms evaluated was spatial memory ( Morris water maze) and the determination of mercury concentration in blood and brain. The data were analysed by two way analyses of variance (ANOVAs). When a significant difference was found, the Student Newman Keuls post hoc test was conducted. The results of the present study demonstrated that exposure to mercury in developmental period induced, significantly decrease of the learning performance (p < 0.01; p < 0.05) compared to control rats. Thus, the concentration of mercury in the intoxicated group is high in the blood and brain. However, the administration of P. anisum essential oil resulted into an improvement of learning perfor-mance (p< 0.01; p< 0.05) and reduction of mercury blood and brain mercury. In conclusion, our results demonstrate that mercury exposure during the developmental period induces learning disabilities and remains trapped in blood and brain. This could be improved by the treatment with Pimpinella anisum essential oil.

Pre-administration of luteoline attenuates neonatal sevoflurane-induced neurotoxicity in mice

Sevoflurane is a widely used inhaled anesthetic, which triggers neuroapoptosis and oxidative damage in the developing central nervous system and cognitive dysfunction later in life. However, no effective therapeutic strategy for sevoflurane-induced deleterious effects is well developed. The purpose of the present study was to explore whether luteoline could attenuate neonatal sevoflurane exposure-triggered neurotoxicity. In this study, six-day-old C57BL/6 mice were pretreated with luteoline (30, 60 mg/kg) intraperitoneally for 30 min before exposed to 3% sevoflurane 6 h consecutively. We first examined the effects of luteoline on hippocampal neuron apoptosis, inflammation and oxidative stress 18 h post anesthesia. The spatial learning and memory performance was measured using Morris water maze test from postnatal day 31 to 38. The results showed that luteoline ameliorated neuronal apoptosis as evidenced by decrease of apoptotic cells, downregulation of the cleavage levels of caspase-3 and PRAP, and inactivation of caspase-3. Moreover, luteoline significantly decreased protein expressions of inflammatory cytokines (IL-1β, IL-18 and TNF-α), inhibited NF-кB/NLRP3 pathway (NF-кB, NLRP3, ASC and caspase-1) and suppressed NF-кB activity. Our analyses indicated that luteoline had a significant effect on decreasing the contents of ROS and MDA, elevating the activity of SOD, and ultimately improving spatial learning and memory deficits of mice. In summary, our findings confirm that the attenuation of luteoline on sevoflurane-induced spatial learning and memory impairment later is associated with inhibition of hippocampal neuron apoptosis, inflammation and oxidative stress early. Luteoline might be a potential therapeutic for sevoflurane anesthesia-induced neurobehavioral dysfunction.

Female mice with apolipoprotein E4 domain interaction demonstrated impairments in spatial learning and memory performance and disruption of hippocampal cyto-architecture.

We have previously reported cognitive impairments in both young and old mice, particularly in female mice expressing mouse Arg-61 apoE, with a point mutation to mimic the domain interaction feature of human apoE4, as compared to the wildtype mouse (C57BL/6J) apoE. In this study, we further evaluated water maze performance in the female Arg-61 mice at an additional time point and then investigated related hippocampal cyto-architecture in these young female Arg-61 apoE mice vs. the wildtype mice. The results of behavioral performance consistently support our previous report that the young female Arg-61 apoE showed cognitive impairment versus C57BL/6J at the same age. The cyto-architectural results showed that volume of the granular cell layer (GCL) was significantly larger in both 5- and 10-month old Arg-61 apoE mice versus C57BL/6J mice. While the number of newborn calretinin-positive neurons was greater in the sub-granular zone (SGZ) in 5-month old Arg-61 mice, this number dropped significantly in 10-month old Arg-61 mice to a lower level than in age-matched C57BL/6J mice. In addition, the amyloid β species was significantly higher in 5-month old Arg-61 mice versus age-matched C57BL/6J mice. In conclusion, impaired cognitive functions in female Arg-61 apoE mice appear correlated with larger GCL volume and higher calretinin-positive cell number and suggest a compensatory cellular response that may be related to amyloid beta perturbations early in life. Therefore this study suggests a novel cyto-architectural mechanism of apoE4-dependent pathologies and increased susceptibility of APOEε4 subjects to Alzheimer's disease.

Attachment Dimensions and Spatial Navigation in Female College Students: The Role of Comfort With Closeness and Confidence in Others.

There is preliminary evidence suggesting that hippocampal functioning is associated with attachment style. However, it is unknown if attachment is also associated with hippocampal-related cognitive function such as spatial learning and recall. This study aims to verify if attachment dimensions are associated with spatial learning and recall. Sixty-five female participants were recruited and were evaluated using the Adult Attachment Scale-R and tested on a virtual maze navigation task (VMT) at one moment (exploratory trial + 3 trials) and 24 h later (3 trials). There was a significant Moment × Trial × Close-Depend interaction for the outcome time, F(2,126) = 3.807, p = 0.025, with post hoc analysis indicating that the High Close-Depend group displayed significant improvements between Trial 1 and Trial 3 in the post-test assessment. Conversely, the Low Close-Depend group displayed significant improvements between Trial 1and Trial 3 but on the pre-test assessment. Furthermore, the Low Close-Depend group presented significant better performance in pre-test Trial 3 in comparison to the High Close-Depend group. Thereby, it seems that low comfort with proximity and trust in others is associated with reduced spatial recall, although spatial learning performance was actually superior in these participants. It is possible that reduced exposure to social interaction and meaningful relationships may be reduced in the Low Close-Depend group, leading to modifications in hippocampal function and, ultimately, reduced spatial recall. Oppositely, participants in the High Close-Depend group may not display typical spatial learning in the proposed task as they are more willing to freely explore the presented environment.

Natural Selection and Spatial Cognition in Wild Food-Caching Mountain Chickadees

Understanding how differences in cognition evolve is one of the critical goals in cognitive ecology [1-5]. In food-caching species that rely on memory to recover caches, enhanced spatial cognition has been hypothesized to evolve via natural selection [2, 6-8], but there has been no direct evidence of natural selection acting on spatial memory. Food-caching mountain chickadees living at harsher, higher elevations, with greater reliance on cached food have better spatial learning abilities and larger hippocampi containing more and larger neurons compared to birds from milder, lower elevations [9, 10]. Here, we tested for natural selection on spatial cognition in wild food-caching mountain chickadees at high elevations and documented the following: (1) compared to first-year juveniles, adults showed significantly better performance on two spatial cognitive tasks-spatial learning and memory and a consecutive reversal learning task; (2) cognitive performance in both spatial learning and reversal learning tasks was not significantly different between years in the same chickadees tested in their first year of life and after surviving to their second winter; and (3) cognitive performance in the spatial learning task was significantly better among the first-year juveniles that survived to their second winter compared to the subset of juveniles that did not survive. Taken together, our results provide evidence for natural selection on spatial cognition in a food-caching species living in harsh environments and suggest that natural selection associated with local environmental conditions might be generating intraspecific differences in cognitive abilities. VIDEO ABSTRACT.

Obvious anxiogenic-like effects of subchronic copper intoxication in rats, outcomes on spatial learning and memory and neuromodulatory potential of curcumin

Copper (Cu) is a transition metal and an essential trace element, but excessive levels of Cu might disturb vital functions and systems including the Central Nervous System (CNS). Curcumin has numerous beneficial effects including protective potential on the CNS toxicity. Previous studies have revealed solid evidence showing metal elements implication in the physiopathology of psychiatric disorders, principally anxiety, as well as association between stressful conditions and the inception of anxiety. In addition, it was stated that stressful condition strengthens memory. The aim of the present study was to evaluate the influence of subchronic Cu-intoxication (0.125%) for 6 weeks on the serotonergic system and anxiety state along with spatial learning and memory performance, then test the therapeutic efficacy of curcumin I (30 mg/kg B.W.). In Cu-exposed rats, we noted a significant increased innervation of 5HT in dorsal raphe nucleus and Basolateral Amygdala (BLA) outputs; this was correlated with an anxiogenic-like effect in rats subjected to elevated plus-maze test. Curcumin co-treatment prevented Cu-induced anxiety and reversed 5-HT alterations. Cu did not alter learning and memory but main spatial learning and memory performance was remarked in treated rats with curcumin in Morris water maze. Results demonstrated that subchronic Cu intoxication induced an evident anxiogenic-like effect that was alleviated with curcumin treatment, then, impairment of monoamine neurotransmitters expression may be one of the major mechanisms implicated. Therefore, curcumin may be valuable in the treatment of anxiety disorders caused by metal elements by acting as an anxiolytic agent, and in the improvement of memory performance.

Prelimbic of Medial Prefrontal Cortex GABA Modulation through Testosterone on Spatial Learning and Memory.

Prefrontal cortex (PFC) is involved in multiple functions including attentional processes, spatial orientation, short-term memory, and long-term memory. Our previous study indicated that microinjection of testosterone in CA1 impaired spatial learning and memory. Some evidence suggests that impairment effect of testosterone is mediated by GABAergic system. In the present study, we investigated the interaction of testosterone (androgenic receptor agonist) and bicuculline (GABAA receptor antagonist) on spatial learning and memory performance in the prelimbic (PL) of male Wistar rats. Cannulae were bilaterally implanted into the PL region of PFC and drugs were daily microinjected for two minutes in each side. There are 4 experiments. In the first experiment, three sham groups were operated (solvent of testosterone, bicuculline, testosterone plus bicuculline). In the second experiment, different doses of testosterone (40, 80 μg /0.5 μL DMSO/each side) were injected into the PL before each session. In the third experiment, intra PL injections of bicuculline (2, 4 μg/0.5 μL DMSO/each side) were given before every session. In the last experiment, testosterone (80μg/0.5 μL DMSO/each side) along with bicuculline (2 μg/0.5 μL DMSO/each side) was injected into the PL. The results showed there is no difference between control group and sham operated group. Testosterone 80 μg and bicuculline 2 μg, each given separately, and also in combination increased escape latency to find the platform compared to the sham operated and cause to impaired spatial learning and memory. It is shown that intra PL microinjection of bicuculline after testosterone treatment could not rescue the spatial learning and memory impaired induced by testosterone.

Investigation the effect of starch-based sugar on spatial memory and learning performance in rats

Investigation the effect of starch-based sugar on spatial memory and learning performance in rats

MMP13 inhibition rescues cognitive decline in Alzheimer transgenic mice via BACE1 regulation.

MMP13 (matrix metallopeptidase 13) plays a key role in bone metabolism and cancer development, but has no known functions in Alzheimer's disease. In this study, we used high-throughput small molecule screening in SH-SY5Y cells that stably expressed a luciferase reporter gene driven by the BACE1 (β-site amyloid precursor protein cleaving enzyme 1) promoter, which included a portion of the 5' untranslated region (5'UTR). We identified that CL82198, a selective inhibitor of MMP13, decreased BACE1 protein levels in cultured neuronal cells. This effect was dependent on PI3K (phosphatidylinositide 3-kinase) signalling, and was unrelated to BACE1 gene transcription and protein degradation. Further, we found that eukaryotic translation initiation factor 4B (eIF4B) played a key role, as the mutation of eIF4B at serine 422 (S422R) or deletion of the BACE1 5'UTR attenuated MMP13-mediated BACE1 regulation. In APPswe/PS1E9 mice, an animal model of Alzheimer's disease, hippocampal Mmp13 knockdown or intraperitoneal CL82198 administration reduced BACE1 protein levels and the related amyloid-β precursor protein processing, amyloid-β load and eIF4B phosphorylation, whereas spatial and associative learning and memory performances were improved. Collectively, MMP13 inhibition/CL82198 treatment exhibited therapeutic potential for Alzheimer's disease, via the translational regulation of BACE1.

Astaxanthin ameliorates scopolamine-induced spatial memory deficit via reduced cortical-striato-hippocampal oxidative stress

Alzheimer’s disease is characterized by progressive disruption of cholinergic neurotransmission and impaired cognitive functions. In rodents, scopolamine has been used to induce cholinergic dysfunction resulting in cognitive impairments and an increment of oxidative stress in the brain. Here we tested whether oxidative stress can be attenuated via an antioxidant (astaxanthin) to rescue scopolamine-induced spatial memory.For this purpose, we administered either 0.9% saline (control), or scopolamine (SCP), or scopolamine plus astaxanthin (SCP + AST) to Swiss albino mice (ten weeks old; n = 20) for 28 consecutive days and subsequently examined animals’ locomotor activity, spatial learning, and memory performance. The mice were then euthanized and prefrontal cortex (PFC), striatum (ST), hippocampus (HP), and liver tissues were assayed for antioxidant enzymes, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and nitric oxide (NO).The SCP group exhibited impaired spatial learning and significantly altered levels of antioxidant enzymes and NO in the PFC, ST, and HP. In contrast, SCP + AST treatment did not cause spatial learning deficits. Furthermore, this condition also showed unaltered levels of SOD and NO in the ST and HP.Taken together, our results show that scopolamine may interrupt the striatal-hippocampal cholinergic activity resulting in impaired spatial memory. At the same time, these impairments are extinguished with astaxanthin by preventing oxidative damage in the striatal-hippocampal cholinergic neurons. Therefore, we suggest astaxanthin as a potential treatment to slow the onset or progression of cognitive dysfunctions that are elicited by abnormal cholinergic neurotransmission in Alzheimer’s disease.

The effect of exposed to radiofrequencry emitted from jammer on the spatial memory

Introduction: The Widespread range of mobile phone application in life has induced many problems in the societies. This subject has caused jammer router is used in some places. Jammer router blocks signal transfer from base station to the cell phone. In the other hand, the extensive application of electromagnetic field in all aspect of life has increased fears and worries about side effects on the human healthy indexes, including learning and memory. Memory can be defined as the skill of saving the experiences and remembering the learned processes or events. This study was used Morris Water Maze Technique to test working spatial memory in rats after exposed to radiation emitted jammer. Materials and Methods: In this study, 50male rats (220-250g) randomly divided 5 groups (n=10): control, sham1&2, Experiment1&2. Experimental groups were irradiated through switched –on mobile phone jammer router2h/day once and other group 2h/day for two weeks’ sequence. This procedure repeated for sham groups but with switched-off jammer router. The distance of animal cages from jammer antenna was 30cm. Learning ability and spatial memory were assessed by Morris Water Maze Technique Sham& Experimental groups were trained 4trails/day during 5 days. Then, data and parameters (latency time, path length) analyzed in different groups for founding the exposure radiation effect from jammer routers on the spatial memory in rats. Results: The analyzed data did show the recorded mean from latency time to reach the hidden platform also the average of path length traveled to reach platform in one- day irradiated groups, as well as, among exposure groups during two weeks were significantly different relative to control. This means radiation emitted of jammer device have reduced learning level in exposure groups compare to control. However, duration exposure radiation 2h/day once or two weeks’ sequence did not show significant difference on the considering parameters. In the other hand, duration exposure radiation 2h/day once or2h daily for two weeks’ sequence did not show significant relationship on the spatial memory and learning performance. Conclusion: Exposure to jammer radiation was impaired spatial memory and learning abilities in exposure rats, but duration radiation did not show statistical significant effect on the learning performance and spatial memory.

GLS1 Mutant Mice Display Moderate Alterations of Hippocampal Glutamatergic Neurotransmission Associated with Specific Adaptive Behavioral Changes

Significant alterations in glutamatergic neurotransmission have been reported in major depressive disorder (MDD) that could underlie psychiatric traits. Studies were mainly interested in synaptic dysfunction in the prefrontal cortex, a key structure involved in depressive-like behavior, however hippocampus has been shown to be important in MDD. As cognitive deficits such as hippocampus-memory process were observed in MDD, we investigated in a mild hypoglutamatergic model behaviors related to depression and memory, synaptic transmission parameters and glutamatergic state specifically in the hippocampus. We thus characterized these phenotypes in adult male mice partially depleted in glutaminase type 1 or GLS1 (GLS1 HET), the enzyme responsible for glutamate synthesis in neurons, that we previously characterized as displaying moderate lower levels of glutamate in brain. We showed that GLS1 mutant mice display AMPA-R-mediated response deficits after prolonged repetitive stimulation with electrophysiological recording and inability to sustain glutamate release by microdialysis experiments with no consequences on behavioral spatial learning performances. However, their ability to escape from unpleasant but repeated escapable condition was attenuated whereas they were more immobile in the unescapable situation in the FST during re-test. These results show that GLS1 mutant mice display moderate impairments of hippocampal glutamatergic neurotransmission and moderate changes in adaptive behaviors that have been shown to participate to the development of depressive-like state.

Entorhinal cortex stimulation induces dentate gyrus neurogenesis through insulin receptor signaling

Deep brain stimulation (DBS) has been established as a therapeutically effective method to treat pharmacological resistant neurological disorders. The molecular and cellular mechanisms underlying the beneficial effects of DBS on the brain are not yet fully understood. Beside numerous suggested mechanisms, regulation of neurogenesis is an attractive mechanism through which DBS can affect the cognitive functions. Considering the high expression of insulin receptors in hippocampus and also impaired neurogenesis in diabetic brain, the present study aimed to examine the role of insulin receptor signaling in DBS induced neurogenesis. High frequency stimulation was applied on the entorhinal cortex of rats and then neurogenesis markers in the dentate gyrus region of the hippocampus were examined using molecular and histological methods in the sham, DBS and insulin receptor antagonist-treated groups. In parallel, the changes in insulin receptor signaling in the hippocampus and spatial learning and memory performance were also assessed. DBS promoted adult hippocampal neurogenesis and facilitated the spatial memory concomitant with changes in insulin receptor signaling parameters including IR, IRS2 and GSK3β. Application of insulin receptor antagonist attenuated the DBS-induced neurogenesis. Our data emphasize that entorhinal cortex stimulation promotes adult hippocampal neurogenesis and facilitates spatial learning and memory at least partly through insulin receptors. Notably, GSK3β inhibition can play a major role in the downstream of insulin receptor signaling in DBS induced neurogenesis.

The relationship between social rank and spatial learning in pheasants, Phasianus colchicus: cause or consequence?

Individual differences in performances on cognitive tasks have been found to differ according to social rank across multiple species. However, it is not clear whether an individual’s cognitive performance is flexible and the result of their current social rank, modulated by social interactions (social state dependent hypothesis), or if it is determined prior to the formation of the social hierarchy and indeed influences an individual’s rank (prior attributes hypothesis). We separated these two hypotheses by measuring learning performance of male pheasants, Phasianus colchicus, on a spatial discrimination task as chicks and again as adults. We inferred adult male social rank from observing agonistic interactions while housed in captive multi-male multi-female groups. Learning performance of adult males was assayed after social rank had been standardised; by housing single males with two or four females. We predicted that if cognitive abilities determine social rank formation we would observe: consistency between chick and adult performances on the cognitive task and chick performance would predict adult social rank. We found that learning performances were consistent from chicks to adults for task accuracy, but not for speed of learning and chick learning performances were not related to adult social rank. Therefore, we could not support the prior attributes hypothesis of cognitive abilities aiding social rank formation. Instead, we found that individual differences in learning performances of adults were predicted by the number of females a male was housed with; males housed with four females had higher levels of learning performance than males housed with two females; and their most recent recording of captive social rank, even though learning performance was assayed while males were in a standardized, non-competitive environment. This does not support the hypothesis that direct social pressures are causing the inter-individual variation in learning performances that we observe. Instead, our results suggest that there may be carry-over effects of aggressive social interactions on learning performance. Consequently, whether early life spatial learning performances influence social rank is unclear but these performances are modulated by the current social environment and a male’s most recent social rank.

Spatial learners display enhanced oculomotor performance

ABSTRACTAttention is important during navigation processes that rely on a cognitive map, as spatial relationships between environmental landmarks need to be selected, encoded, and learned. Spatial learners navigate using this process of cognitive map formation, which relies on the hippocampus. Conversely, response learners memorise a series of actions to navigate, which relies on the caudate nucleus. The present study aimed to investigate the relationship between spatial learning and oculomotor performance. We tested 23 response learners and 23 spatial learners, as determined by the 4-on-8 virtual maze, on an antisaccade task with a gap and emotional visual stimulus manipulation. Spatial learners displayed decreased saccadic reaction time latencies compared to response learners. Performance cost from the gap manipulation was significantly higher in response learners. These results could represent an attentional practice effect through the use of spatial strategies during navigation or a more global increase in cognitive function amongst spatial learners.

Role of astaxanthin in the modulation of brain-derived neurotrophic factor and spatial learning behavior in perinatally undernourished Wistar rats

Objective: Maternal health and nutrition during the perinatal period is the predominant factor influencing the functional development of the brain. Maternal malnutrition during the perinatal period causes retardation of brain development. The current study investigates the role of Astaxanthin (AsX) in spatial learning and memory and BDNF in perinatally undernourished Wistar rats.Methods: The albino wistar rats were perinatally undernourished and administered with different dosages of AsX. The spatial learning and memory performance and BDNF level were assessed. Data were collected and analysed.Results: The % Correct choice during the acquisition phase, performance at the end of the acquisition phase and the mean BDNF level at the Hippocampus, Cerebellum, and Cerebral cortex showed significant decline (P<0.001) in the PUN group and significantly high (P<0.001) in the PUNA2 group compared to the control. However, the mean RME and mean WME during different days of the acquisition phase were significantly high (P<0.001) in the PUN group and insignificant (P>0.05) in PUNA2 compared to the control.Discussion: The results showed that AsX effectively modulated the cognitive deficit that occurred in perinatally undernourished rats. This can be attributed to BDNF upregulation as evidenced by the significant increase of the BDNF level.

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice.

Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment. However, whether folate deficiency could cause T2D and subsequent cognitive dysfunction is still unknown. The present study aimed to explore the effects of chronic folate deficiency (CFD) on glucose and lipid metabolism and cognitive function in mice. Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment. In addition, CFD reduced the hepatic p-Akt/Akt ratio in response to acute insulin administration. Moreover, CFD increased serum triglyceride levels, upregulated hepatic Acc1 and Fasn mRNA expression, and downregulated hepatic Cd36 and ApoB mRNA expression. After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance. This study demonstrates that folate deficiency could induce obesity, glucose and lipid metabolism disorders and subsequent cognitive dysfunction.

Daily foraging routines in food-caching mountain chickadees are associated with variation in environmental harshness

Small birds overwintering in cold climates must meet the daily challenge of accumulating sufficient energy reserves throughout the day to ensure overnight survival. Theoretical work suggests that risk of starvation is a major force shaping optimal daily foraging routines. Animals are predicted to adjust how they distribute their daily foraging activity in relation to environmental harshness, which largely determines the risk of starvation. Here, we used radiofrequency identification (RFID)-enabled bird feeders to test whether mountain chickadees, Poecile gambeli – small, resident, food-caching birds – exhibited different daily foraging routines in harsher (higher elevation) versus milder (lower elevation) environments in the Sierra Nevada. In addition, we assessed foraging routines between four different periods of the nonbreeding season ranging from autumn (milder conditions) to winter and early spring (harsher conditions) and to late spring (milder conditions). We also tested whether individual variation in spatial cognition associated with food caching, which represents a more reliable food source that can be expected to lower risk of starvation, is associated with differences in daily foraging routines. Chickadees from both elevations distributed their daily foraging efforts differently throughout the nonbreeding season, consistent with theoretical predictions for milder and harsher conditions. Differences between chickadees from high and low elevations were especially pronounced during harsher winter periods, with chickadees from high elevations showing a bimodal daily routine, while low-elevation birds showed an inverted U-shaped daily routine, with most foraging during the middle of the day. Finally, significant differences in daily routines were associated with variation in spatial learning and memory performance. Overall, our study shows that daily foraging routines are consistent with risk of starvation under different degrees of environmental harshness, whether across nonbreeding seasons or between elevations, and that perception of harshness may be associated with cognitive abilities.

Unilateral whisker pad injection of botulinum toxin type a enhances spatial learning in mice.

The central cholinergic nervous system plays an important role in cognition, with acetylcholine hypofunction considered to be a major factor of dementia. Botulinum toxin type A (BoNT/A), a potent poison secreted by Clostridium botulinum, is used widely for dystonia treatment and facial cosmesis. BoNT/A injection inhibits acetylcholine release in the neuromuscular junction through cleavage of synaptosomal-associated protein of 25 kDa in cholinergic terminals. Furthermore, beyond the injection site, BoNT/A undergoes retrograde transport and transcytosis to the central nervous system from peripheral cholinergic terminals. However, whether peripheral BoNT/A injection affects the function of the central nervous system and induces learning deficits remains unclear. We injected mice with different doses of BoNT/A (2, 10, and 50 U/kg) or sterile saline (control) into the left whisker pad to test spatial learning performance at different times after injection using the Morris water maze. At 3 days and 4 weeks after injection, the spatial learning ability of the control and BoNT/A-treated mice showed no significant differences. Surprisingly, however, rather than spatial learning impairment at 6 weeks after injection, BoNT/A-treated mice spent less time than control mice in locating the experimental platform, indicating that BoNT/A facial injection might promote spatial learning. Furthermore, our study suggests that facial application of BoNT/A is safe and could play a positive role in ameliorating the spatial learning deficits associated with neurodegenerative diseases.