A New Plant Active Polysaccharide from Nicotiana Improves the Lead-Led Impairment of Spatial Memory in Mice by Modulating the Gut Microbiota and IL-6.

Active polysaccharides from plants are broadly applied in the food and health industry. The purpose of this study is to identify a new plant active polysaccharide and to investigate its role in modulating spatial memory. Ultrasonics and DEAE-52 chromatography were used to separate and purify the plant active polysaccharide (PAP). Mice were exposed to 100 ppm of lead acetate from birth to 7 weeks old to establish the memory impairment model. PAPs with concentrations of 200 or 400 ppm were fed to the subject mice each day after weaning in a spatiotemporally separated fashion. At the end of the intervention, mice were examined using the Morris water maze test, microbiome sequencing, cytokine profiling and protein analysis. The derived active polysaccharide was constituted by ß-anomeric carbon, indicating a new form of PAP. The PAP significantly ameliorates the memory impairment caused by postnatal lead exposure, as evidenced by the preferred coverage of the test mouse in the hidden platform, demonstrating salient neuroregulatory activity. In terms of the gut microbiome in response to PAP treatment, it was found that the 400 ppm PAP reversed the gut dysbiosis, producing a comparable structure to the intact animals, represented by the relative abundance of Firmicutes and Muribaculum, Desulfovibrio, etc. For cytokines, the PAP reversed the plasma levels of IL-6, suggesting an anti-inflammatory trend in the context of proinflammation caused by lead invasion. By injecting an IL-6 antagonist, Tocilizumab, into the deficient mice, the spatial memory was significantly repaired, which demonstrates the central roles of IL-6 in mediating the positive effect of the PAP. Finally, a histone modification mark, H3K27me3, was found to be potent in responding to the signals conveyed by the PAP. The PAP could improve the memory deficits by remodeling the gut-brain axis centered at the microbiota and IL-6, which is regarded as an important cytokine-modulating brain activity. This is an intriguing instance linking neuromodulation with the active polysaccharide, shedding light on the innovative applications of plant polysaccharides due to the scarcity of similar phenotypic connections.

Assessment of cFos labeling in the hippocampus and anterior cingulate cortex following recent and remote re-exposure to an unreinforced open field in preadolescent and postadolescent rats.

Spatial tasks are often goal-directed or reward-facilitated confounding the assessment of "pure" recent and remote spatial memories. The current work re-exposed preadolescent and postadolescent male rats to a non-reinforced, free exploration task to investigate cFos patterns within the hippocampus and anterior cingulate cortex (ACC) associated with recent and remote periods. Male rats were exposed to an open field task for one, 30 min session on postnatal day (P) 20, 25, or 50 and re-exposed for 30 min at either a recent (24 hours) or remote (3 weeks) timepoint. Distance traveled in the open field was measured as well as cFos labeling. In the P20 age group, there was elevated exploration at the 24-hour and 3-week tests compared to training and compared to the other age groups. In the hippocampus CA1, cFos levels were higher after the remote test than the recent test in the P20 group but higher after the recent test than remote test in the P25 and P50 groups. cFos labeling in the ACC was higher in all remote-tested groups compared to the recent-tested groups across all ages. In the P20, the 24-hour test was associated with less CA1 activity than the other age groups supporting the hypothesis that the hippocampus is not fully developed at this time point. In the P20 group, the remote representation of this task did not seem to be complete as there continued to be CA1 activity along with ACC activity following the remote test associated with elevated exploration. These results indicate the utility of unreinforced spatial navigation tasks for exploring systems consolidation processes over the lifespan and show that a fully developed hippocampus is required for optimal systems consolidation.

Investigating Olfactory Sensory Neurons Facilitation For Aerobic Exercise-induced Spatial Memory Improvement.

Introduction: The positive effects of exercise on spatial memory and learning have been demonstrated in research. The olfactory sensory neurons (OSNs) respond to mechanical stimulation induced by nasal airflow which is associated with airflow intensity. Accordingly, nasal breathing can modulate brain oscillations in nonolfactory areas, and respiration-entrained oscillations aid the improvement of cognitive abilities. Given that aerobic exercise increases the rate of respiration and intensity of nasal airflow, this study evaluates the role of OSNs in mediating the effects of aerobic exercise on memory. Methods: We examined spatial memory following exercise in animal models of olfactory sensory neuron impairment (methimazole injection 300 mg/kg/week). Results: Destroying OSNs significantly reduces olfactory bulb (OB) activity at delta and theta frequency bands as well as its coupling to respiration. More importantly, it abolished the positive effect of exercise on spatial memory (P<0.05). Conclusion: The OB activity is one of the probable mechanisms for improving spatial memory following exercise.

Clausena harmandiana root extract ameliorates Aß1-42 induced cognitive deficits, oxidative stress, and apoptosis in rats.

BACKGROUND: Clausena harmandiana (CH), commonly known as song fa dong, was a medicinal plant traditionally used to treat illnesses and as a health tonic. CH root extract (CHRE) exhibited various bioactivities, including neuroprotective, antioxidant, antimicrobial, antifungal, anti-inflammatory, and anti-cancer effects. However, CHRE data on neuroprotective in AD-like animal models were still scarce. OBJECTIVES: This study aimed to investigate the effects of CHRE on Aß1-42-induced cognitive deficits, free radical damage, and neuronal death in rats. METHODS: Forty-eight adult male Sprague-Dawley rats (250-300 g) were classified as sham control (SC), V+Aß, Vit C+Aß, CHRE125+Aß, CHRE250+Aß, and CHRE500+Aß (n = 8 in each group). Animals were orally administered with 0.5% sodium carboxymethylcellulose, vitamin C (200 mg/kg BW), or CHRE (125, 250, and 500 mg/kg BW) and were untreated for 35 days. On day 21, all treated rats were injected with 1 µl of aggregated Aß1-42 (1 µg/µl) into the lateral ventricles, bilaterally, whereas untreated rats were injected with sterilized normal saline (NS). The Morris water maze test estimated the rat's learning and memory one week later. At the end of the treatment, all rats were sacrificed, and their brains were removed and divided into two hemispheres. On the left, morphological changes and neuronal density were observed in hippocampal CA1 and CA3 regions. While, on the right, changes in free radical damage markers (SOD, CAT, GPx, MDA, and Nrf2) and protein expression of active caspase-3 were evaluated in the hippocampus. RESULTS: Pretreatment with CHRE at all doses could alleviate spatial learning and memory defects. CHRE also improved morphological changes and a decrease in neuronal density in CA1 and CA3 regions. Additionally, CHRE significantly increased the activities of antioxidant enzymes (SOD, CAT, GPx) and Nrf2 expression. This was coupled with significantly decreased MDA levels and active caspase-3 expression in the hippocampus of Aß1-42-induced rats, which was similar to vitamin C exposure. CONCLUSIONS: Our findings suggested that CHRE ameliorated cognitive deficits and exhibited neuroprotective effects by reducing free radical damage and mitigating neuronal abnormality and neuronal death.

Developmental 17-OHPC exposure disrupts behavior regulated by the mesocorticolimbic dopaminergic system in rats.

The synthetic progestin, 17α-hydroxyprogesterone caproate (17-OHPC), is administered to pregnant individuals with the intention of reducing preterm birth. Although there is evidence that 17-OHPC is likely transferred from mother to fetus, there is little information regarding the potential effects of 17-OHPC administration on behavioral and neural development in offspring. Neonatal 17-OHPC exposure disrupts the development of the mesocorticolimbic dopaminergic pathway and associated behaviors in rats. 17-OHPC exposure altered dopaminergic innervation of prelimbic medial prefrontal cortex (mPFC) in neonates and adolescents and altered performance in measures of decision-making, set-shifting, and reversal-learning tasks. The present study tested the effects of developmental 17-OHPC exposure on numerous cognitive behaviors mediated by the mesocorticolimbic dopaminergic system, such as decision-making in a delay discounting task, latent inhibition following conditioned taste aversion (CTA), and spatial memory in the Morris Water Maze (MWM). The present work also aimed to further investigate response omissions in rats exposed to 17-OHPC during development and the potential role of dopamine D2 receptor in altering omissions in a delay discounting task. 17-OHPC exposure rendered rats less sensitive to an Eticlopride-induced increase in omissions in a delay discounting task when compared to controls. Quinpirole flattened the discount curve in both groups but did not significantly affect omissions in 17-OHPC-exposed or control rats. Following CTA, sucrose-pre-exposed 17-OHPC-exposed rats demonstrated decreased latent inhibition when compared to controls. In Morris Water Maze testing, 17-OHPC-exposed rats did not differ from controls after the first day of testing or during probe testing. These results suggest that exposure to 17-OHPC altered aspects of decision-making and latent inhibition in adult male rats, without affecting performance in a measure of spatial learning and memory. Further, the insensitivity of 17-OHPC-exposed males to an Eticlopride-induced increase in omissions suggests a dysfunction in the D2 receptor following exposure to this clinically used synthetic progestin.

Proteomic evidence for seed odor modifying olfaction and spatial memory in a scatter-hoarding animal.

Seed odor plays a crucial role in affecting the scatter-hoarding behavior of small rodents that rely on spatial memory and olfaction to cache and recover. However, evidence of how seed odor modifies olfaction function and spatial memory is still lacking. Here, we coated seeds with waterproof glue to test how seed odor intensity alters the proteome of both the olfactory bulbs and hippocampus of a dominant scatter-hoarding rodent, Leopoldamys edwardsi, in Southwest China. We showed that animals repeatedly caching and recovering weak odor seeds exhibited greater olfactory ability and spatial memory, as indicated by alterations in the protein profiles of the olfactory bulbs and hippocampus. The upregulation of proteins closely related to neural connections between the olfactory bulb and hippocampus is highly responsible for improved olfactory function and spatial memory. Our study provides new insights into how scatter-hoarding rodents manage and respond to cached seeds differing in odor intensity from a neurobiological perspective, which is of significant importance for better understanding the parallel evolution of the olfactory and hippocampal systems.

Melatonin Supplementation Alleviates Impaired Spatial Memory by Influencing Aß1-42 Metabolism via γ-Secretase in the icvAß1-42 Rat Model with Pinealectomy.

In the search for Alzheimer's disease (AD) therapies, most animal models focus on familial AD, which accounts for a small fraction of cases. The majority of AD cases arise from stress factors, such as oxidative stress, leading to neurological changes (sporadic AD). Early in AD progression, dysfunction in γ-secretase causes the formation of insoluble Aß1-42 peptides, which aggregate into senile plaques, triggering neurodegeneration, cognitive decline, and circadian rhythm disturbances. To better model sporadic AD, we used a new AD rat model induced by intracerebroventricular administration of Aß1-42 oligomers (icvAß1-42) combined with melatonin deficiency via pinealectomy (pin). We validated this model by assessing spatial memory using the radial arm maze test and measuring Aß1-42 and γ-secretase levels in the frontal cortex and hippocampus with ELISA. The icvAß1-42 + pin model experienced impaired spatial memory and increased Aß1-42 and γ-secretase levels in the frontal cortex and hippocampus, effects not seen with either icvAß1-42 or the pin alone. Chronic melatonin treatment reversed memory deficits and reduced Aß1-42 and γ-secretase levels in both structures. Our findings suggest that our icvAß1-42 + pin model is extremely valuable for future AD research.

Neuroprotective effects of Daphnetin on hippocampal neurons and blood-brain barrier integrity in a mouse model of cerebral ischemia.

The purpose of this research was to assess the impact of different doses of Daphnetin (DAP, a natural compound derived from coumarin) on hippocampus neuronal injury, neurobehavioral function, blood-brain barrier (BBB) integrity, expression of claudin-5, brain-derived neurotrophic factor (BDNF), superoxide dismutase (SOD), and inflammatory markers in a mouse model of cerebral ischemia. Cerebral ischemia was induced in mice through 30minutes of bilateral common carotid occlusion (BCCAO), followed by 48hours of reperfusion. The viability of hippocampal neurons was assessed using Cresyl violet staining and BBB function was determined by measuring Evans blue (E.B) dye leakage. Spatial memory was tested using the Radial Arm Water Maze (RAWM) task. Claudin-5 and BDNF were measured by immunofluorescence, while SOD, interleukin-1 beta (IL-1ß), and nuclear factor-κB (NF-κB) expression were determined through western blotting. Administering DAP significantly increased neuron survival in the hippocampus CA1, CA3, and dentate gyrus (DG) regions and improved spatial memory dose-dependently (P<0.0001). Treatment with DAP (40mg/kg IP) significantly reduced E.B leakage and brain water content (P<0.001). Furthermore, it increased the claudin-5, BDNF, and SOD levels and diminished NF-κB and IL-1ß expression (P<0.0001). The research found that DAP protected neurons in the CA1, CA3, and DG areas of the hippocampus, enhanced behavioral functions, and preserved BBB integrity in a cerebral ischemia model. This positive impact is achieved by increasing the expression of claudin-5, BDNF, and SOD and diminishing neuroinflammation. Further research is required to clarify the mechanisms and possible clinical uses.

Role of BIX01294 in the intracranial inhibition of H3K9 methylation lessens neuronal loss in vascular dementia model.

Dementia develops as a result of multiple factors, including cerebrovascular disease which is called vascular dementia (VD). Histone-3 lysine-9 dimethylation (H3K9me2) broadly increases during VD and inhibits neuroprotective gene expressions. So, we aimed to determine how H3K9me2 inhibitor (BIX01294) affects neuronal damage in VD. An in vivo model of VD was used followed by BIX01294 treatment. Behavioral tests, hematoxylin, and eosin (H&E), Congo red, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were carried out. Hippocampal phosphorylated cyclic-AMP responsive element binding protein (p-CREB), c-fos, brain-derived neurotrophic factor (BDNF), and H3K9me2, were detected by western blot analysis technique. Neurological deficit and anxiety-related behavior significantly reduced in the treatment group compared to the VD group (p < 0.05). BIX01294 improved spatial and passive avoidance memory (p < 0.01 and p < 0.05, respectively) compared to the VD group. Treatment with BIX01294 restored the level of p-CREB/CREB ratio (p < 0.05), cfos (p < 0.01), BDNF (p < 0.01), and suppressed H3K9me2 (p < 0.001) when compared to the VD group. BIX01294 microinjection reduced the apoptosis level in TUNEL staining (p < 0.05), and raised neural cell count in H&E staining (p < 0.01); amyloid beta accumulation significantly decreased in the treatment group (p < 0.05) compared to the VD group. In conclusion, long-term treatment with a low dose of BIX01294 can prevent the progression of neuronal loss in VD model by raising the expression of neurotrophic factors, and reducing the apoptosis level.

Unreliable association between self-reported sense of direction and peripheral vestibular function.

BACKGROUND: Uni- or bilateral peripheralvestibular impairment causes objective spatial orientation deficits, which can be measured using pen-and-paper-tests or sensorimotor tasks (navigation or pointing). For patients' subjective orientation abilities, questionnaires are commonly used (e.g., Santa Barbara sense of direction scale [SBSODS]). However, the relationship between subjective assessment of spatial skills and objective vestibular function has only been scarcely investigated. METHODS: A total of 177 patients (mean age 57.86 ± 17.53 years, 90 females) who presented in our tertiary Center for Vertigo and Balance Disorders underwent neuro-otological examinations, including bithermal water calorics, video head impulse test (vHIT), and testing of the subjective visual vertical (SVV), and filled out the SBSODS (German version). Correlation analyses and linear multiple regression model analyses were performed between vestibular test results and self-assessment scores. Additionally, groupwise vestibular function for patients with low, average, and high self-report scores was analyzed. RESULTS: Forty-two patients fulfilled the diagnostic criteria for bilateral vestibulopathy, 93 for chronic unilateral vestibulopathy (68 unilateral caloric hypofunction and 25 isolated horizontal vestibulo-ocular reflex deficits), and 42 patients had normal vestibular test results. SBSODS scores showed clear sex differences with higher subjective skill levels in males (mean score males: 4.94 ± 0.99, females 4.40 ± 0.94; Student's t-test: t-3.78, p < .001***). No stable correlation between objective vestibular function and subjective sense of spatial orientation was found. A multiple linear regression model could not reliably explain the self-reported variance. The three patient groups with low, average, and high self-assessment-scores showed no significant differences of vestibular function. CONCLUSION: Self-reported assessment of spatial orientation does not robustly correlate with objective peripheral vestibular function. Therefore, other methods of measuring spatial skills in real-world and virtual environments are required to disclose orientation deficits due to vestibular hypofunction.

Genetic patterning in hippocampus of rat undergoing impaired spatial memory induced by long-term heat stress.

The organism's normal physiological function is greatly impacted in a febrile environment, leading to the manifestation of pathological conditions including elevated body temperature, dehydration, gastric bleeding, and spermatogenic dysfunction. Numerous lines of evidence indicate that heat stress significantly impacts the brain's structure and function. Previous studies have demonstrated that both animals and humans experience cognitive impairment as a result of exposure to high temperatures. However, there is a lack of research on the effects of prolonged exposure to high-temperature environments on learning and memory function, as well as the underlying molecular regulatory mechanisms. In this study, we examined the impact of long-term heat stress exposure on spatial memory function in rats and conducted transcriptome sequencing analysis of rat hippocampal tissues to identify the crucial molecular targets affected by prolonged heat stress exposure. It was found that the long-term heat stress impaired rats' spatial memory function due to the pathological damages and apoptosis of hippocampal neurons at the CA3 region, which is accompanied with the decrease of growth hormone level in peripheral blood. RNA sequencing analysis revealed the signaling pathways related to positive regulation of external stimulation response and innate immune response were dramatically affected by heat stress. Among the verified differentially expressed genes, the knockdown of Arhgap36 in neuronal cell line HT22 significantly enhances the cell apoptosis, suggesting the impaired spatial memory induced by long-term heat stress may at least partially be mediated by the dysregulation of Arhgap36 in hippocampal neurons. The uncovered relationship between molecular changes in the hippocampus and behavioral alterations induced by long-term heat stress may offer valuable insights for the development of therapeutic targets and protective drugs to enhance memory function in heat-exposed individuals.

Spatial memory and learning: investigating the role of dynamic visual acuity.

Introduction: The vestibular system's contribution to spatial learning and memory abilities may be clarified using the virtual Morris Water Maze Task (vMWMT). This is important because of the connections between the vestibular system and the hippocampus area. However, there is ongoing debate over the role of the vestibular system in developing spatial abilities. This study aimed to evaluate the relationship between Dynamic Visual Acuity (DVA) across three planes and spatial abilities. Methods: This cross-sectional study was conducted with 50 healthy adults aged 18 to 55 with normal stress levels and mental health and no neurological, audiological, or vestibular complaints. The Trail-Making Test (TMT) Forms A and B for the assessment of executive functions, the DVA test battery for the evaluation of visual motor functions, and the Virtual Morris Water Maze Test (vMWMT) for the assessment of spatial learning and spatial memory were performed. All participants also underwent the Benton Face Recognition Test (BFRT) and Digit Symbol Substitution Tests (DSST) to assess their relation with spatial memory. Results: DVA values in horizontal (H-DVA), vertical (V-DVA), and sagittal (S-DVA) planes ranged from (-0.26) to 0.36 logMAR, (-0.20) to 0.36 logMAR, and (-0.28) to 0.33 logMAR, respectively. The latency of three planes of DVA was affected by vMWMT (Horizontal, Vertical, and Sagittal; Estimate: 22.733, 18.787, 13.341, respectively p < 0.001). Moreover, a moderately significant correlation was also found, with a value of 0.571 between the Virtual MWM test and BFRT and a value of 0.539 between the DSST (p < 0.001). Conclusion: Spatial abilities in healthy adults were significantly influenced by dynamic visual functions across horizontal, vertical, and sagittal planes. These findings are expected to trigger essential discussions about the mechanisms that connect the vestibular-visual system to the hippocampus. The original vMWMT protocol is likely to serve as a model for future studies utilizing this technology.

Cacao Ameliorates Amyloid Beta-Induced Cognitive and Non-Cognitive Disturbances.

Background: Alzheimer's disease (AD) is a progressive neurological disorder characterized by a wide range of cognitive and non-cognitive impairments. The present study was designed to investigate the potential effects of cacao on cognitive and non-cognitive performance and to identify the role of oxidative stress in an AD animal model induced by unilateral intracerebroventricular (U-ICV) injection of amyloid beta1-42 (Aß1-42). Methods: Oral administration of cacao (0.5 g/kg/day) was performed for 60 consecutive days. Following 60 days, the open-field (OF) test, elevated plus-maze (EPM) test, novel object recognition (NOR) test, Barnes maze (BM) test, and Morris water maze (MWM) test were used to evaluate locomotor activity, anxiety-like behavior, recognition memory, and spatial memory, respectively. Total oxidant status (TOS) and total antioxidant capacity (TAC) in plasma were also examined. Furthermore, the number of healthy cells in the hippocampus's dentate gyrus (DG), CA1, and CA3 regions were identified using hematoxylin and eosin staining. Results: The results indicated that the injection of Aß1-42 in rats led to recognition memory and spatial memory impairments, as well as increased anxiety. This was accompanied by decreased total antioxidant capacity (TAC), increased total oxidative stress (TOS), and increased neuronal death. Conversely, cacao treatment in AD rats improved memory function, reduced anxiety, modulated oxidative stress balance, and decreased neuronal death. Conclusion: The findings suggest that cacao's ability to improve the balance between oxidants and antioxidants and prevent neuronal loss may be the mechanism underlying its beneficial effect against AD-related cognitive and non-cognitive impairments.

The Individual Division of Food Hoarding in Autumn Brandt's Voles (Lasiopodomys brandtii).

Brandt's voles (Lasiopodomys brandtii), one of the main non-hibernating rodent species in the typical grassland of Inner Mongolia, live in groups and have the behavioral habit of hoarding food in underground warehouses in autumn to prepare for the winter food shortage ahead. The division of labor and cooperation are typical behavior patterns of gregarious mammals, but it is unclear whether Brandt's voles exercise a division of labor in food hoarding before overwintering. To explore the division of food hoarding in Brandt's voles during the autumn period, three treatments, namely added food, added food + competition, and control, were set up with three replicates. An infrared camera was positioned to observe and record the behavior of Brandt's voles under different treatments. Next, behavioral experiments regarding food-hoarding division were performed on individuals. The results showed that (1) Brandt's voles had two types of hoarding behavior, namely high food hoarding and low food hoarding, but not all individuals displayed hoarding behavior. (2) In all treatments, feeding behavior, which was the most important type of behavior, accounted for the highest proportion of all behaviors. (3) There was no significant difference in body weight and sex between high- and low-food-hoarding individuals of Brandt's voles, and there was no significant difference between high- and low-food-hoarding individuals in other divisions of labor either. (4) There was no significant difference in inquiry ability between high- and low-food-hoarding groups, but there was a significant difference in spatial memory. High-food-hoarding individuals had greater spatial memory. In summary, Brandt's voles had two types of hoarding behavior: high food hoarding and low food hoarding. Furthermore, high-food-hoarding individuals had greater spatial memory.

Spatial memory obviates following behaviour in an information centre of wild fruit bats.

According to the information centre hypothesis (ICH), colonial species use social information in roosts to locate ephemeral resources. Validating the ICH necessitates showing that uninformed individuals follow informed ones to the new resource. However, following behaviour may not be essential when individuals have a good memory of the resources' locations. For instance, Egyptian fruit bats forage on spatially predictable trees, but some bear fruit at unpredictable times. These circumstances suggest an alternative ICH pathway in which bats learn when fruits emerge from social cues in the roost but then use spatial memory to locate them without following conspecifics. Here, using an unique field manipulation and high-frequency tracking data, we test for this alternative pathway: we introduced bats smeared with the fruit odour of the unpredictably fruiting Ficus sycomorus trees to the roost, when they bore no fruits, and then tracked the movement of conspecifics exposed to the manipulated social cue. As predicted, bats visited the F. sycomorus trees with significantly higher probabilities than during routine foraging trips (of >200 bats). Our results show how the integration of spatial memory and social cues leads to efficient resource tracking and highlight the value of using large movement datasets and field experiments in behavioural ecology. This article is part of the theme issue 'The spatial-social interface: a theoretical and empirical integration'.

Photoperiod, food restriction and memory for objects and places in mice.

The suprachiasmatic nucleus (SCN) contains a population of cell-autonomous circadian oscillators essential for entrainment to daily light-dark (LD) cycles. Synchrony among SCN oscillators is modified by photoperiod and determines functional properties of SCN clock cycling, including its amplitude, phase angle of entrainment, and free running periodicity (τ). For many species, encoding of daylength in SCN output is critical for seasonal regulation of metabolism and reproduction. C57BL/6 mice do not show seasonality in these functions, yet do show photoperiodic modulation of SCN clock output. The significance of this for brain systems and functions downstream from the SCN in these species is largely unexplored. C57BL/6 mice housed in a long-day photoperiod have been reported to perform better on tests of object, spatial and fear memory compared to mice in a standard 12 h photoperiod. We previously reported that encoding of photoperiod in SCN output, evident in τ in constant dark (DD), can be blocked by limiting food access to a 4 h mealtime in the light period. To determine whether this might also block the effect of long days on memory, mice entrained to 18 h:6 h (L18) or 6 h:18 h (L6) LD cycles were tested for 24 h object memory (novel object preference, NOP) and spatial working memory (Y-maze spontaneous alternation, SA), at 4 times of day, first with food available ad libitum and then during weeks 5-8 of daytime restricted feeding. Photoperiod modified τ as expected, but did not affect performance on the NOP and SA tests, either before or during restricted feeding. NOP performance did improve in the restricted feeding condition in both photoperiods, eliminating a weak time of day effect evident with food available ad-libitum. These results highlight benefits of restricted feeding on cognitive function, and suggest a dose-response relationship between photoperiod and memory, with no benefits at daylengths up to 18 h.

Dopamine D1 receptors activation rescues hippocampal synaptic plasticity and cognitive impairments in the MK-801 neonatal schizophrenia model.

Schizophrenia is a disorder with a higher cognitive decline in early adulthood, causing impaired retention of episodic memories. However, the physiological and behavioral functions that underlie cognitive deficits with a potential mechanism to ameliorate and improve cognitive performance are unknown. In this study, we used the MK-801 neurodevelopmental schizophrenia-like model. Rats were divided into two groups: one received MK-801, and the other received saline for five consecutive days (7-11 postnatal days, PND). We evaluated synaptic plasticity late-LTP and spatial memory consolidation in early adolescence and young adulthood using extracellular field recordings in acute hippocampal slices and the Barnes maze task. Next, we examined D1 receptor (D1R) activation as a mechanism to ameliorate cognitive impairments. Our results suggest that MK-801 neonatal treatment induces impairment in late-LTP expression and deficits in spatial memory retrieval in early adolescence that is maintained until young adulthood. Furthermore, we found that activation of dopamine D1R ameliorates the impairments and promotes a robust expression of late-LTP and an improved performance in the Barnes maze task, suggesting a novel and potential therapeutic role in treating cognitive impairments in schizophrenia.

Neonatal Cannabidiol Exposure Impairs Spatial Memory and Disrupts Neuronal Dendritic Morphology in Young Adult Rats.

Introduction: Early life is a sensitive period for brain development. Perinatal exposure to cannabis is increasingly linked to disruption of neurodevelopment; however, research on the effects of cannabidiol (CBD) on the developing brain is scarce. In this study, we aim to study the developmental effects of neonatal CBD exposure on behavior and dendritic architecture in young adult rats. Materials and Methods: Male and female neonatal Sprague Dawley rats were treated with CBD (50 mg/kg) intraperitoneally on postnatal day (PND) 1, 3, and 5 and evaluated for behavioral and neuronal morphological changes during early adulthood. Rats were subjected to a series of behavioral tasks to evaluate long-term effects of neonatal CBD exposure, including the Barnes maze, open field, and elevated plus maze paradigms to assess spatial memory and anxiety-like behavior. Following behavioral evaluation, animals were sacrificed, and neuronal morphology of the cortex and hippocampus was assessed using Golgi-Cox (GC) staining. Results: Rats treated with CBD displayed a sexually dimorphic response in spatial memory, with CBD-treated females developing a deficit but not males. CBD did not elicit alterations in anxiety-like behavior in either sex. Neonatal CBD caused an overall decrease in dendritic length and spine density (apical and basal) in cortical and hippocampal neurons in both sexes. Sholl analysis also revealed a decrease in dendritic intersections in the cortex and hippocampus, indicating reduced dendritic arborization. Conclusions: This study provides evidence that neonatal CBD exposure perturbs normal brain development and leads to lasting alterations in spatial memory and neuronal dendrite morphology in early adulthood, with sex-dependent sensitivity.

Image memorability influences memory for where the item was seen but not when.

Observers can determine whether they have previously seen hundreds of images with more than 80% accuracy. This "massive memory" for WHAT we have seen is accompanied by smaller but still massive memories for WHERE and WHEN the item was seen (spatial & temporal massive memory). Recent studies have shown that certain images are more easily remembered than others (higher "memorability"). Does memorability influence spatial massive memory and temporal massive memory? In two experiments, viewers saw 150 images presented twice in random order. These 300 images were sequentially presented at random locations in a 7 × 7 grid. If an image was categorized as old, observers clicked on the spot in the grid where they thought they had previously seen it. They also noted when they had seen it: Experiment 1-clicking on a timeline; Experiment 2-estimating the trial number when the item first appeared. Replicating prior work, data show that high-memorability images are remembered better than low-memorability images. Interestingly, in both experiments, spatial memory precision was correlated with image memorability, while temporal memory precision did not vary as a function of memorability. Apparently, properties that make images memorable help us remember WHERE but not WHEN those images were presented. The lack of correlation between memorability and temporal memory is, of course, a negative result and should be treated with caution.

Revisiting serotonin's role in spatial memory: A call for sensitive analytical approaches.

The serotonergic system is involved in various psychiatric and neurological conditions, with serotonergic drugs often used in treatment. These conditions frequently affect spatial memory, which can serve as a model of declarative memory due to well-known cellular components and advanced methods that track neural activity and behavior with high temporal resolution. However, most findings on serotonin's effects on spatial learning and memory come from studies lacking refined analytical techniques and modern approaches needed to uncover the underlying neuronal mechanisms. This In Focus review critically investigates available studies to identify areas for further exploration. It finds that well-established behavioral models could yield more insights with modern tracking and data analysis approaches, while the cellular aspects of spatial memory remain underexplored. The review highlights the complex role of serotonin in spatial memory, which holds the potential for better understanding and treating memory-related disorders.