Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The 5HT2b Receptor in Alzheimer's Disease: Increased Levels in Patient Brains and Antagonist Attenuation of Amyloid and Tau Induced Dysfunction.

BACKGROUND: Background: Neurodegenerative diseases manifest behavioral dysfunction with disease progression. Intervention with neuropsychiatric drugs is part of most multi-drug treatment paradigms. However, only a fraction of patients responds to the treatments and those responding must deal with drug-drug interactions and tolerance issues generally attributed to off-target activities. Recent efforts have focused on the identification of underexplored targets and exploration of improved outcomes by treatment with selective molecular probes. Objective: As part of ongoing efforts to identify and validate additional targets amenable to therapeutic intervention, we examined levels of the serotonin 5-HT2b receptor (5-HT2bR) in Alzheimer's disease (AD) brains and the potential of a selective 5-HT2bR antagonist to counteract synaptic plasticity and memory damage induced by AD-related proteins, amyloid-ß, and tau. Methods: This work used a combination of biochemical, chemical biology, electrophysiological, and behavioral techniques. Biochemical methods included analysis of protein levels. Chemical biology methods included the use of an in vivo molecular probe MW071, a selective antagonist for the 5HT2bR. Electrophysiological methods included assessment of long-term potentiation (LTP), a type of synaptic plasticity thought to underlie memory formation. Behavioral studies investigated spatial memory and associative memory. Results: 5HT2bR levels are increased in brain specimens of AD patients compared to controls. 5HT2bR antagonist treatment rescued amyloid-ß and tau oligomer-induced impairment of synaptic plasticity and memory. Conclusions: The increased levels of 5HT-2bR in AD patient brains and the attenuation of disease-related synaptic and behavioral dysfunctions by MW071 treatment suggest that the 5HT-2bR is a molecular target worth pursuing as a potential therapeutic target.

Event-related theta and gamma band oscillatory dynamics during visuo-spatial sequence memory in younger and older adults.

Visuo-spatial working memory (VSWM) for sequences is thought to be crucial for daily behaviors. Decades of research indicate that oscillations in the gamma and theta bands play important functional roles in the support of visuo-spatial working memory, but the vast majority of that research emphasizes measures of neural activity during memory retention. The primary aims of the present study were (1) to determine whether oscillatory dynamics in the Theta and Gamma ranges would reflect item-level sequence encoding during a computerized spatial span task, (2) to determine whether item-level sequence recall is also related to these neural oscillations, and (3) to determine the nature of potential changes to these processes in healthy cognitive aging. Results indicate that VSWM sequence encoding is related to later (∼700 ms) gamma band oscillatory dynamics and may be preserved in healthy older adults; high gamma power over midline frontal and posterior sites increased monotonically as items were added to the spatial sequence in both age groups. Item-level oscillatory dynamics during the recall of VSWM sequences were related only to theta-gamma phase amplitude coupling (PAC), which increased monotonically with serial position in both age groups. Results suggest that, despite a general decrease in frontal theta power during VSWM sequence recall in older adults, gamma band dynamics during encoding and theta-gamma PAC during retrieval play unique roles in VSWM and that the processes they reflect may be spared in healthy aging.

A hippocampus-accumbens code guides goal-directed appetitive behavior.

The dorsal hippocampus (dHPC) is a key brain region for the expression of spatial memories, such as navigating towards a learned reward location. The nucleus accumbens (NAc) is a prominent projection target of dHPC and implicated in value-based action selection. Yet, the contents of the dHPC→NAc information stream and their acute role in behavior remain largely unknown. Here, we found that optogenetic stimulation of the dHPC→NAc pathway while mice navigated towards a learned reward location was both necessary and sufficient for spatial memory-related appetitive behaviors. To understand the task-relevant coding properties of individual NAc-projecting hippocampal neurons (dHPC→NAc), we used in vivo dual-color two-photon imaging. In contrast to other dHPC neurons, the dHPC→NAc subpopulation contained more place cells, with enriched spatial tuning properties. This subpopulation also showed enhanced coding of non-spatial task-relevant behaviors such as deceleration and appetitive licking. A generalized linear model revealed enhanced conjunctive coding in dHPC→NAc neurons which improved the identification of the reward zone. We propose that dHPC routes specific reward-related spatial and behavioral state information to guide NAc action selection.

Semantic partitioning facilitates memory for object location through category-partition cueing.

In our lived environments, objects are often semantically organised (e.g., cookware and cutlery are placed close together in the kitchen). Across four experiments, we examined how semantic partitions (that group same-category objects in space) influenced memory for object locations. Participants learned the locations of items in a semantically partitioned display (where each partition contained objects from a single category) as well as a purely visually partitioned display (where each partition contained a scrambled assortment of objects from different categories). Semantic partitions significantly improved location memory accuracy compared to the scrambled display. However, when the correct partition was cued (highlighted) to participants during recall, performance on the semantically partitioned display was similar to the scrambled display. These results suggest that semantic partitions largely benefit memory for location by enhancing the ability to use the given category as a cue for a visually partitioned area (e.g., toys - top left). Our results demonstrate that semantically structured spaces help location memory across partitions, but not items within a partition, providing new insights into the interaction between meaning and memory.

Variaciones de las células de cuadrícula y de posicionamiento de la corteza entorrinal y del giro dentado de 6 humanos de 56 a 87 años / Variations of the grid and place cells in the entorhinal cortex and dentate gyrus of 6 individuals aged 56 to 87 years

Introducción: La relación entre la corteza entorrinal y el hipocampo ha sido estudiada por diferentes autores, que han destacado la importancia de las células de cuadrícula, las células de posicionamiento y la conexión trisináptica en los procesos que regulan: la persistencia de la memoria espacial, explícita y reciente, y su posible afección con el envejecimiento. Objetivo: Observar si existen diferencias en el tamaño y número de células de cuadrícula contenidas en la lámina iii de la corteza entorrinal y en la capa granular del giro dentado del hipocampo de pacientes mayores. Métodos: Realizamos estudios posmortem del cerebro de 6 sujetos de edades comprendidas entre los 56 y 87 años. Los cortes de cerebros que contenían el giro dentado del hipocampo y la corteza entorrinal adyacente se tiñeron con el método de Klüver-Barrera, después se midió, mediante el programa Image J, el área neuronal individual, el área neuronal total, así como el número de neuronas, contenidas en cuadrículas rectangulares a nivel de la lámina iii de la corteza entorrinal y la lámina ii del giro dentado y se llevó a cabo un análisis estadístico. Resultados: Se ha observado una reducción de la población celular de la capa piramidal externa de la corteza entorrinal, así como de las neuronas de la capa granular del giro dentado relacionada con el envejecimiento. Conclusión: Nuestros resultados indican que el envejecimiento produce una disminución en el tamaño y la densidad neuronal en las células de cuadrícula de la corteza entorrinal y de posicionamiento del giro dentado.(AU)

Introduction: The relationship between the entorhinal cortex and the hippocampus has been studied by different authors, who have highlighted the importance of grid cells, place cells, and the trisynaptic circuit in the processes that they regulate: the persistence of spatial, explicit, and recent memory and their possible impairment with ageing. Objective: We aimed to determine whether older age causes changes in the size and number of grid cells contained in layer III of the entorhinal cortex and in the granular layer of the dentate gyrus of the hippocampus. Methods: We conducted post-mortem studies of the brains of 6 individuals aged 56-87 years. The brain sections containing the dentate gyrus and the adjacent entorhinal cortex were stained according to the Klüver-Barrera method, then the Image J software was used to measure the individual neuronal area, the total neuronal area, and the number of neurons contained in rectangular areas in layer III of the entorhinal cortex and layer II of the dentate gyrus. Statistical analysis was subsequently performed. Results: We observed an age-related reduction in the cell population of the external pyramidal layer of the entorhinal cortex, and in the number of neurons in the granular layer of the dentate gyrus. Conclusion: Our results indicate that ageing causes a decrease in the size and density of grid cells of the entorhinal cortex and place cells of the dentate gyrus.(AU)

A persistent prefrontal reference frame across time and task rules.

Behavior can be remarkably consistent, even over extended time periods, yet whether this is reflected in stable or 'drifting' neuronal responses to task features remains controversial. Here, we find a persistently active ensemble of neurons in the medial prefrontal cortex (mPFC) of mice that reliably maintains trajectory-specific tuning over several weeks while performing an olfaction-guided spatial memory task. This task-specific reference frame is stabilized during learning, upon which repeatedly active neurons show little representational drift and maintain their trajectory-specific tuning across long pauses in task exposure and across repeated changes in cue-target location pairings. These data thus suggest a 'core ensemble' of prefrontal neurons forming a reference frame of task-relevant space for the performance of consistent behavior over extended periods of time.

Spatial working memory in a disappearing object task is impaired in female but not male dogs with chronic osteoarthritis.

Chronic pain in humans is associated with impaired working memory but it is not known whether this is the case in long-lived companion animals, such as dogs, who are especially vulnerable to developing age-related chronic pain conditions. Pain-related impairment of cognitive function could have detrimental effects on an animal's ability to engage with its owners and environment or to respond to training or novel situations, which may in turn affect its quality of life. This study compared the performance of 20 dogs with chronic pain from osteoarthritis and 21 healthy control dogs in a disappearing object task of spatial working memory. Female neutered osteoarthritic dogs, but not male neutered osteoarthritic dogs, were found to have lower predicted probabilities of successfully performing the task compared to control dogs of the same sex. In addition, as memory retention interval in the task increased, osteoarthritic dogs showed a steeper decline in working memory performance than control dogs. This suggests that the effects of osteoarthritis, and potentially other pain-related conditions, on cognitive function are more clearly revealed in tasks that present a greater cognitive load. Our finding that chronic pain from osteoarthritis may be associated with impaired working memory in dogs parallels results from studies of human chronic pain disorders. That female dogs may be particularly prone to these effects warrants further investigation.

Hippocampal subfield plasticity is associated with improved spatial memory.

Physical exercise studies are generally underrepresented in young adulthood. Seventeen subjects were randomized into an intervention group (24.2 ± 3.9 years; 3 trainings/week) and 10 subjects into a passive control group (23.7 ± 4.2 years), over a duration of 6 months. Every two months, performance diagnostics, computerized spatial memory tests, and 3 Tesla magnetic resonance imaging were conducted. Here we find that the intervention group, compared to controls, showed increased cardiorespiratory fitness, spatial memory performance and subregional hippocampal volumes over time. Time-by-condition interactions occurred in right cornu ammonis 4 body and (trend only) dentate gyrus, left hippocampal tail and left subiculum. Increases in spatial memory performance correlated with hippocampal body volume changes and, subregionally, with left subicular volume changes. In conclusion, findings support earlier reports of exercise-induced subregional hippocampal volume changes. Such exercise-related plasticity may not only be of interest for young adults with clinical disorders of hippocampal function, but also for sedentary normal cohorts.

Amylovis-201 enhances physiological memory formation and rescues memory and hippocampal cell loss in a streptozotocin-induced Alzheimer's disease animal model.

Alzheimer's disease is the most common neurodegenerative disease, and its treatment is lacking. In this work, we tested Amylovis-201, a naphthalene-derived compound, as a possible therapeutic candidate for the treatment of AD. For this purpose, we performed three experiments. In the first and third experiment, animals received a bilateral administration of streptozotocin and, starting 24 h after injection, a daily dose of Amylovis-201 (orally), for 17 days or for the whole time of the experiment respectively (28 days), after which learning and memory, as well as the number of hippocampal dentate gyrus cells, were assessed. In the second experiment, healthy animals received a single dose of Amylovis-201, 10 min or 5 h after the learning section to assess whether this substance could promote specific mechanisms involved in memory trace formation. Our data show that, administration of a single dose of Amylovis-201, 10 min after the end of training, but not at 5 h, produces a prolongation in memory duration, probably because it modulates specific mechanisms involved in memory trace consolidation. Furthermore, daily administration of Amylovis-201 to animals with bilateral intracerebroventricular injection of STZ produces a reduction in the loss of the hippocampus dentate gyrus cells and an improvement in spatial memory, probably because Amylovis-201 can interact with some of the protein kinases of the insulin signaling cascade, also involved in neural plasticity, and thereby halt or reverse some of the effects of STZ. Taking to account these results, Amylovis-201 is a good candidate for the therapeutic treatment of AD.

Efficient encoding of aversive location by CA3 long-range projections.

Memorizing locations that are harmful or dangerous is a key capability of all organisms and requires an integration of affective and spatial information. In mammals, the dorsal hippocampus mainly processes spatial information, while the intermediate to ventral hippocampal divisions receive affective information via the amygdala. However, how spatial and aversive information is integrated is currently unknown. To address this question, we recorded the activity of hippocampal long-range CA3 axons at single-axon resolution in mice forming an aversive spatial memory. We show that intermediate CA3 to dorsal CA3 (i-dCA3) projections rapidly overrepresent areas preceding the location of an aversive stimulus due to a spatially selective addition of new place-coding axons followed by spatially non-specific stabilization. This sequence significantly improves the encoding of location by the i-dCA3 axon population. These results suggest that i-dCA3 axons transmit a precise, denoised, and stable signal indicating imminent danger to the dorsal hippocampus.

Hippocampal lesions impair non-navigational spatial memory in macaques.

Decades of studies robustly support a critical role for the hippocampus in spatial memory across a wide range of species. Hippocampal damage produces clear and consistent deficits in allocentric spatial memory that requires navigating through space in rodents, non-human primates, and humans. By contrast, damage to the hippocampus spares performance in most non-navigational spatial memory tasks-which can typically be resolved using egocentric cues. We previously found that transient inactivation of the hippocampus impairs performance in the Hamilton Search Task (HST), a self-ordered non-navigational spatial search task. A key question, however, still needs to be addressed. Acute, reversible inactivation of the hippocampus may have resulted in an impairment in the HST because this approach does not allow for neuroplastic compensation, may prevent the development of an alternative learning strategy, and/or may produce network-based effects that disrupt performance. We compared learning and performance on the HST in male rhesus macaques (six unoperated control animals and six animals that underwent excitotoxic lesions of the hippocampus). We found a significant impairment in animals with hippocampal lesions. While control animals improved in performance over the course of 45 days of training, performance in animals with hippocampal lesions remained at chance levels. The HST thus represents a sensitive assay for probing the integrity of the hippocampus in non-human primates. These data provide evidence demonstrating that the hippocampus is critical for this type of non-navigational spatial memory, and help to reconcile the many null findings previously reported.

Disruption of awake sharp-wave ripples does not affect memorization of locations in repeated-acquisition spatial memory tasks.

Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay - a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.

Positive modulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors differentially alters spatial learning and memory in juvenile rats younger and older than three weeks.

Remarkable performance improvements occur at the end of the third postnatal week in rodents tested in various tasks that require navigation according to spatial context. While alterations in hippocampal function at least partially subserve this cognitive advancement, physiological explanations remain incomplete. Previously, we discovered that developmental modifications to hippocampal glutamatergic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in juvenile rats was related to more mature spontaneous alternation behavior in a symmetrical Y-maze. Moreover, a positive allosteric modulator of AMPA receptors enabled immature rats to alternate at rates seen in older animals, suggesting an excitatory synaptic limitation to hippocampal maturation. We then validated the Barnes maze for juvenile rats in order to test the effects of positive AMPA receptor modulation on a goal-directed spatial memory task. Here we report the effects of the AMPA receptor modulator, CX614, on spatial learning and memory in the Barnes maze. Similar to our prior report, animals just over 3 weeks of age display substantial improvements in learning and memory performance parameters compared to animals just under 3 weeks of age. A moderate dose of CX614 enabled immature animals to move more directly to the goal location, but only after 1 day of training. This performance improvement was observed on the second day of training with drug delivery or during a memory probe trial performed without drug delivery after the second day of training. Higher doses created more search errors, especially in more mature animals. Overall, CX614 provided modest performance benefits for immature rats in a goal-directed spatial memory task.

Impairments in the early consolidation of spatial memories via group II mGluR agonism in the mammillary bodies.

mGluR2 receptors are widely expressed in limbic brain regions associated with memory, including the hippocampal formation, retrosplenial and frontal cortices, as well as subcortical regions including the mammillary bodies. mGluR2/3 agonists have been proposed as potential therapeutics for neurological and psychiatric disorders, however, there is still little known about the role of these receptors in cognitive processes, including memory consolidation. To address this, we assessed the effect of the mGluR2/3 agonist, eglumetad, on spatial memory consolidation in both mice and rats. Using the novel place preference paradigm, we found that post-sample injections of eglumetad impaired subsequent spatial discrimination when tested 6 h later. Using the immediate early gene c-fos as a marker of neural activity, we showed that eglumetad injections reduced activity in a network of limbic brain regions including the hippocampus and mammillary bodies. To determine whether the systemic effects could be replicated with more targeted manipulations, we performed post-sample infusions of the mGluR2/3 agonist 2R,4R-APDC into the mammillary bodies. This impaired novelty discrimination on a place preference task and an object-in-place task, again highlighting the role of mGluR2/3 transmission in memory consolidation and demonstrating the crucial involvement of the mammillary bodies in post-encoding processing of spatial information.

Context memory formed in medial prefrontal cortex during infancy enhances learning in adulthood.

Adult behavior is commonly thought to be shaped by early-life experience, although episodes experienced during infancy appear to be forgotten. Exposing male rats during infancy to discrete spatial experience we show that these rats in adulthood are significantly better at forming a spatial memory than control rats without such infantile experience. We moreover show that the adult rats' improved spatial memory capability is mainly based on memory for context information during the infantile experiences. Infantile spatial experience increased c-Fos activity at memory testing during adulthood in the prelimbic medial prefrontal cortex (mPFC), but not in the hippocampus. Inhibiting prelimbic mPFC at testing during adulthood abolished the enhancing effect of infantile spatial experience on learning. Adult spatial memory capability only benefitted from spatial experience occurring during the sensitive period of infancy, but not when occurring later during childhood, and when sleep followed the infantile experience. In conclusion, the infantile brain, by a sleep-dependent mechanism, favors consolidation of memory for the context in which episodes are experienced. These representations comprise mPFC regions and context-dependently facilitate learning in adulthood.

A Blended Vitamin Supplement Improves Spatial Cognitive and Short-Term Memory in Aged Mice.

Although many types of antioxidant supplements are available, the effect is greater if multiple types are taken simultaneously rather than one type. However, it is difficult to know which type and how much to take, as it is possible to take too many of some vitamins. As it is difficult for general consumers to make this choice, it is important to provide information based on scientific evidence. This study investigated the various effects of continuous administration of a blended supplement to aging mice. In 18-month-old C57BL/6 mice given a blended supplement ad libitum for 1 month, spatial cognition and short-term memory in the Morris water maze and Y-maze improved compared with the normal aged mice (spontaneous alternative ratio, normal aged mice, 49.5%, supplement-treated mice, 68.67%, p < 0.01). No significant differences in brain levels of secreted neurotrophic factors, such as nerve growth factor and brain-derived neurotrophic factor, were observed between these two groups. In treadmill durability tests before and after administration, the rate of increase in running distance after administration was significantly higher than that of the untreated group (increase rate, normal aged mice, 91.17%, supplement-treated aged mice, 111.4%, p < 0.04). However, training had no reinforcing effect, and post-mortem serum tests showed a significant decrease in aspartate aminotransferase, alanine aminotransferase, and total cholesterol values. These results suggest continuous intake of a blended supplement may improve cognitive function and suppress age-related muscle decline.

Learning shapes the development of migratory behavior.

How animals refine migratory behavior over their lifetime (i.e., the ontogeny of migration) is an enduring question with important implications for predicting the adaptive capacity of migrants in a changing world. Yet, our inability to monitor the movements of individuals from early life onward has limited our understanding of the ontogeny of migration. The exploration-refinement hypothesis posits that learning shapes the ontogeny of migration in long-lived species, resulting in greater exploratory behavior early in life followed by more rapid and direct movement during later life. We test the exploration-refinement hypothesis by examining how white storks (Ciconia ciconia) balance energy, time, and information as they develop and refine migratory behavior during the first years of life. Here, we show that young birds reduce energy expenditure during flight while also increasing information gain by exploring new places during migration. As the birds age and gain more experience, older individuals stop exploring new places and instead move more quickly and directly, resulting in greater energy expenditure during migratory flight. During spring migration, individuals innovated novel shortcuts during the transition from early life into adulthood, suggesting a reliance on spatial memory acquired through learning. These incremental refinements in migratory behavior provide support for the importance of individual learning within a lifetime in the ontogeny of long-distance migration.

Patients with Parkinson's disease demonstrate deficits in visual-spatial memory in the Chinese Visual Retention Test.

OBJECTIVE: We aimed to explore the existence of visual-spatial memory deficit in patients with Parkinson's disease (PD) without dementia in the Chinese Visual Retention Test, as well as to assess whether their performance is related to age, duration, severity, stage, and dopamine (DA) dose. METHODS: Forty-two patients with PD and 30 healthy controls were included in our study. The Chinese Visual Retention Test was used to evaluate the visual-spatial memory of the subjects. Parameters of the Chinese Visual Retention Test were compared between the two groups. Correlation analysis and multiple linear regression analysis were used to explore the associations of the Chinese Visual Retention Test with age, duration, severity, stage of PD, and DA dose. RESULTS: Three correct scores in the Chinese Visual Retention Test were all significantly lower in the PD group than in the control group. The total error scores, error scores of omissions, deformation, and persistence in the PD group were significantly higher than those in the control group. Correlation analysis showed the total error scores in the Chinese Visual Retention Test was positively correlated with UPDRS III score and H-Y classification. Multiple linear regression analysis showed that the total error scores in the Chinese Visual Retention Test were associated with the UPDRS III score and H-Y classification. CONCLUSION: Patients with PD without dementia had visual-spatial memory deficits in the Chinese Visual Retention Test which may be affected by the severity and clinical stage of PD.

Morin improves learning and memory in healthy adult mice.

BACKGROUND: Morin is a flavonoid found in many edible fruits. The hippocampus and entorhinal cortex play crucial roles in memory formation and consolidation. This study aimed to characterize the effect of morin on recognition and space memory in healthy C57BL/6 adult mice and explore the underlying molecular mechanism. METHODS: Morin was administered i.p. at 1, 2.5, and 5 mg/kg/24 h for 10 days. The Morris water maze (MWM), novel object recognition, novel context recognition, and tasks were conducted 1 day after the last administration. The mice's brains underwent histological characterization, and their protein expression was examined using immunohistochemistry and Western blot techniques. RESULTS: In the MWM and novel object recognition tests, mice treated with 1 mg/kg of morin exhibited a significant recognition index increase compared to the control group. Besides, they demonstrated faster memory acquisition during MWM training. Additionally, the expression of pro-brain-derived neurotrophic factor (BDNF), BDNF, and postsynaptic density protein 95 proteins in the hippocampus of treated mice showed a significant increase. In the entorhinal cortex, only the pro-BDNF increased. Morin-treated mice exhibited a significant increase in the hippocampus's number and length of dendrites. CONCLUSION: This study shows that morin improves recognition memory and spatial memory in healthy adult mice.