The time, the path, its length and strenuousness in maze learning

Previous findings show that rats in a maze tend to choose the shortest path to reach food. But it is not clear whether this choice is based on path length solely, or some other factors. The aim of this experiment was to investigate which factor dominates the behavior in a maze: path (longer and shorter), time (longer and shorter), or effort (more or less strenuous). The experiment involved 40 mice (4 groups), learning a maze with two paths. Each group went through only one of the situations within which we kept one factor constant on two paths while the remaining two factors were varied. Only in the fourth situation all factors were equalized. The results show that there is a statistically significant difference in the maze path preference between four situations. Preference between the paths is such that mice always choose paths requiring less effort.

Homeopathy as a tool for enhancing Cognition in Senescence/Senility: Experimental Model.

Background: Several comparative and experimental studies have shown that elder subjects show performance significantly prejudiced in different types of cognitive tasks1. The aging process is extremely complex and multifactorial, due to its multidisciplinary nature. Therefore, it is greatly important to study medications that can reduce the losses induced by aging in men and animals. Aim: The objective of this study was to evaluate the action of homeopathic medication in locomotion and enhancement of cognitive tasks, prejudiced by senescence/senility in rats. Materials and Method: 32 Wistar rats were used, all male, 22 to 23 months old of age, from the Santo Amaro University (UNISA) Bioterium. According to Andreollo et al. (2012)2 and Segunpta et al. (2013)3, a Wistar rat at the age of this study can be compared to a human over 60 years old. However, in laboratory conditions, hardly ever an animal (Wistar rat) reaches this age, therefore, research mice are considered elderly. The number of animals chosen for this study was in accordance with the 3Rs rules (Reduction, Refinement, Replacement - www.nc3rs.org.uk/ARRIVE). All males were maintained in cages with ad libitum access to food and water, in a controlled light cycle of 12:12 hours (7h/19h). Medications were made based on the Brazilian Homeopathy Pharmacopeia. The animals were distributed randomly in 4 experimental groups (4/cage), with 8 animals per group, and the following medications were administered in the drinking water ad libitum (5 drops/drinking bottle): Calcarea carbonica 30 cH; Baryta muriática 30 cH; Hydro alcoholic solution 10%; White Control (no medication). The experiment was conducted in blind and the medications used in code, only revealed after the statistics were conducted. The animals were weighed weekly and were subjected to Open Field (OF) on day 1 of the experiment; after 40 days of medication the animals were subjected to the Open Field (OF) test and to “T” Maze learning test4. Data were analyzed statistically by ANOVA, followed by the Bartlett's Test and Bonferroni's Multiple Comparison Test and Kruskal Wallis e Dunn, being p≤0.05. Results and Discussion: All groups lost weight during the experiment except the group Calcarea carbonica, that gained weight (p≤0.05). In the beginning of the experiment there was no statistical difference between groups in OF, demonstrating uniformity amongst animals. After medication, when subjected to OF, it was observed an increase of the walking quadrants (p≤0.05) in total locomotion and decreased of Freezing in the groups treated with Carcarea carbonica e Baryta muriatica (p≤0.05) relative to the White Control and Hydro alcoholic solution groups, demonstrating better disposition of the medicated elderly. It is known that aging accelerates neurodegenerative processes, leading to cognitive dysfunctions5, however in the “T” Maze test learning test, it was seen an increased correct responses in the group treated with Baryta muriatica 30 cH, suggesting enhancing the elderly’s memory5. Conclusion: The drugs were able to increase the locomotion of animals and Baryta muriatica improved the cognitive responses in animals compared to the other groups.

The effect of rearing conditions during the milk-fed period on milk yield, growth, and maze behaviour of dairy cows during their first lactation

The objective was to find whether cow growth, milk performance, and behaviour are affected by (1) rearing conditions until weaning after a milk-fed period of 84 d and (2) the sire lineage. Thirty-five Holstein heifers were assigned to one of three treatments: SM, n=13, pen with mother to 21st day, then group pen (they received a maximum of 6 kg of milk daily); SN, n=9, after 3 d with own mother in pen with nursing cow (they received a maximum of 6 kg of milk daily); H, n=13, in hutch from the 2nd to 56th day (6 kg of milk replacer daily), then loose housing pen to weaning (6 kg of milk replacer daily). After weaning at the 84th day, all heifers were kept in pens with the same ration as during calving. During lactation, live body weight (LBW) was measured each month and milk yield each day. Maze learning was evaluated in the fifth month of lactation. The data were analysed using a general linear model ANOVA. At the 30th day, the LBW tended to be the highest in SN (SM 528.2 ± 11.4 kg, SN 571.7 ± 15.3 kg, H 533.2 ± 12.3 kg). When lactation ended, the highest LBW was in SN and the lowest in H (SM 612.6 ± 12.2 kg, SN 623.1 ± 16.4 kg, H 569.8 ± 13.2 kg; P<0.05). The SN tended to have the highest production of milk (SM 7143.9 ± 241.5 kg, SN 7345.1 ± 319.0 kg, H 7146.7 ± 234 kg), and the H for FCM (SM 6290.3 ± 203.2 kg, SN 6307.6 ± 268.4 kg, H 6399.3 ± 197.1 kg) for 305 d lactation. Group SN crossed the maze fastest (SM 1141.4 ± 120.5 s, SN 810.3 ± 160.5 s, H 1120.8 ± 118.6 s). The vocalization number differed significantly (SM 32.3 ± 5.7, SN 20.8 ± 4.4, H 9.9 ± 2.6; P<0.01). The results indicated that the rearing method up to weaning may have an impact on dairy cows' performance and behaviour.

Hearing Aid Uptake, Benefit, and Use: The Impact of Hearing, Cognition, and Personal Factors

Purpose The purpose of this study was to explore the effects of hearing, cognition, and personal factors on hearing aid (HA) uptake, use, and benefit. Method Eighty-five older adults aged 60–80 years ( M = 70.23, SD = 5.17) participated in the study. Hearing was assessed using pure-tone audiometry and the Listening in Spatialised Noise–Sentences test. Cognition was measured using the Cogstate Brief Battery and the Cogstate Groton Maze Learning task. Personal demographics were recorded from participants' answers on a series of take-home questionnaires. HA benefit and use was subjectively reported at 3 and 6 months post HA fitting for those who chose to use HAs. Results Stepwise-regression and mixed-effects models indicated that stronger psychomotor function predicted greater reported use of HAs at 3 and 6 months post HA fitting. Greater family interaction scores also predicted greater HA use at 3 months after fitting. Participants who chose to be fitted with HAs had significantly poorer self-reported health and poorer audiometric thresholds. Poorer hearing was also significantly related with greater reported HA benefit. Conclusions A combination of cognitive, psychosocial factors and hearing impacted HA outcomes for the older Australians in this study. Self-reported HA use was significantly greater in participants with better psychomotor function. Furthermore, those with poorer self-reported health were more likely to choose to use HAs. These factors should be considered in audiological rehabilitation to best maximize patient HA outcomes.

Cognitive aging is associated with redistribution of synaptic weights in the hippocampus

Behaviors that rely on the hippocampus are particularly susceptible to chronological aging, with many aged animals (including humans) maintaining cognition at a young adult-like level, but many others the same age showing marked impairments. It is unclear whether the ability to maintain cognition over time is attributable to brain maintenance, sufficient cognitive reserve, compensatory changes in network function, or some combination thereof. While network dysfunction within the hippocampal circuit of aged, learning-impaired animals is well-documented, its neurobiological substrates remain elusive. Here we show that the synaptic architecture of hippocampal regions CA1 and CA3 is maintained in a young adult-like state in aged rats that performed comparably to their young adult counterparts in both trace eyeblink conditioning and Morris water maze learning. In contrast, among learning-impaired, but equally aged rats, we found that a redistribution of synaptic weights amplifies the influence of autoassociational connections among CA3 pyramidal neurons, yet reduces the synaptic input onto these same neurons from the dentate gyrus. Notably, synapses within hippocampal region CA1 showed no group differences regardless of cognitive ability. Taking the data together, we find the imbalanced synaptic weights within hippocampal CA3 provide a substrate that can explain the abnormal firing characteristics of both CA3 and CA1 pyramidal neurons in aged, learning-impaired rats. Furthermore, our work provides some clarity with regard to how some animals cognitively age successfully, while others’ lifespans outlast their “mindspans.”

Identifying Dyslexia: Link between Maze Learning and Dyslexia Susceptibility Gene, DCDC2, in Young Children

Dyslexia is a common learning disability that affects processing of written language despite adequate intelligence and educational background. If learning disabilities remain untreated, a child may experience long-term social and emotional problems, which influence future success in all aspects of their life. Dyslexia has a 60% heritability rate, and genetic studies have identified multiple dyslexia susceptibility genes (DSGs). DSGs, such as <i>DCDC2</i>, are consistently associated with the risk and severity of reading disability (RD). Altered neural connectivity within temporoparietal regions of the brain is associated with specific variants of DSGs in individuals with RD. Genetically altering DSG expression in mice results in visual and auditory processing deficits as well as neurophysiological and neuroanatomical disruptions. Previously, we demonstrated that learning deficits associated with RD can be translated across species using virtual environments. In this 2-year longitudinal study, we demonstrate that performance on a virtual Hebb-Williams maze in pre-readers is able to predict future reading impairment, and the genetic risk strengthens, but is not dependent on, this relationship. Due to the lack of oral reporting and use of letters, this easy-to-use tool may be particularly valuable in a remote working environment as well as working with vulnerable populations such as English language learners.

Unraveling Early Signs of Navigational Impairment in APPswe/PS1dE9 Mice Using Morris Water Maze

Mild behavioral deficits, which are part of normal aging, can be early indicators of an impending Alzheimer's disease. Using the APPswe/PS1dE9 (APP/PS1) mouse model of Alzheimer's disease, we utilized the Morris water maze spatial learning paradigm to systematically evaluate mild behavioral deficits that occur during the early stages of disease pathogenesis. Conventional behavioral analysis using this model indicates that spatial memory is intact at 2 months of age. In this study, we used an alternative method to analyze the behavior of mice, aiming to gain a better understanding of the nature of cognitive deficits by focusing on the unsuccessful trials during water maze learning rather than on the successful ones. APP/PS1 mice displayed a higher number of unsuccessful trials during the initial days of training, unlike their wild-type counterparts. However, with repeated trial and error, learning in APP/PS1 reached levels comparable to that of the wild-type mice during the later days of training. Individual APP/PS1 mice preferred a non-cognitive search strategy called circling, which led to abrupt learning transitions and an increased number of unsuccessful trials. These findings indicate the significance of subtle intermediate readouts as early indicators of conditions such as Alzheimer's disease.

The effects of acute dopamine reuptake inhibition on cognitive function during passive hyperthermia

Dopamine activity can modulate physical performance in the heat, but less is known about its effects on cognition during thermal stress. Twelves males completed a randomized, double-blinded protocol consisting of oral ingestion of 20 mg of methylphenidate (MPH) or placebo (lactose pill) during passive heating using a water-perfused suit (water temperature ~49°C). To identify the impact of peripheral versus central thermal strain, a cognitive test battery was completed at four different thermal states: baseline (BASE; 37.2±0.6˚C core, 32.9±0.7˚C skin), neutral core-hot skin (NC-HS; 37.2±0.3˚C, 37.4±0.3˚C), hyperthermic core-hot skin (HC-HS; 38.7±0.4˚C, 38.7±0.2˚C), and hyperthermic core-cooled skin (HC-CS; 38.5±0.4˚C, 35.1±0.8˚C). The cognitive test battery consisted of the 2-back task (i.e. working memory), set-shifting (i.e. executive function), Groton Maze Learning Task (i.e. executive function) and detection task (i.e. psychomotor processing). MPH led to significantly higher heart rates (~5-15 b·min-1) at BASE, NC-HS, and HC-HS (all p<0.05). There were no significant differences in the number of errors made on each task (all p<0.05). Participants were significantly faster (p<0.05) on the set-shifting task in the HC-HS timepoint, irrespective of drug condition (p>0.05). In summary, we demonstrated that 20 mg of MPH did not significantly alter cognitive function during either normothermia or moderate hyperthermia. Novelty: ● 20 mg of MPH did not significantly alter cognitive function during passive heat stress ● MPH led to significant higher heart rates (~5-15 bmin-1) in thermoneutral and during passive heat stress ● Future studies are needed to determine the mechanisms of why MPH improves physical but not cognitive performance during heat stress

Strategy-Specific Patterns of Arc Expression in the Retrosplenial Cortex and Hippocampus during T-Maze Learning in Rats

The retrosplenial cortex (RSC) belongs to the spatial memory circuit, but the precise timeline of its involvement and the relation to hippocampal activation have not been sufficiently described. We trained rats in a modified version of the T maze with transparent walls and distant visual cues to induce the formation of allocentric spatial memory. We used two distinct salient contexts associated with opposite sequences of turns. Switching between contexts allowed us to test the ability of animals to utilize spatial information. We then applied a CatFISH approach with a probe directed against the Arc immediate early gene in order to visualize the associated memory engrams in the RSC and the hippocampus. After training, rats displayed two strategies to solve the maze, with half of the animals relying on distant spatial cues (allocentric) and the other half using egocentric strategy. Rats that did not utilize the spatial cues showed higher Arc levels in the RSC compared to the allocentric group. The overlap between the two context engrams in the RSC was similar in both groups. These results show differential involvement of the RSC and hippocampus during spatial memory acquisition and point toward their distinct roles in forming the cognitive maps.