Prenatal treatment with corticosterone via maternal injection induces learning and memory impairments via delaying postsynaptic development in hippocampal CA1 neurons of rats.

Previously, we reported that prenatal exposure to high corticosterone induced attention-deficit hyperactivity disorder (ADHD)-like behaviors with cognitive deficits after weaning. In the present study, cellular mechanisms underlying cortisol-induced cognitive dysfunction were investigated using rat pups (Corti.Pups) born from rat mothers that were repetitively injected with corticosterone during pregnancy. In results, Corti.Pups exhibited the failure of behavioral memory formation in the Morris water maze (MWM) test and the incomplete long-term potentiation (LTP) of hippocampal CA1 neurons. Additionally, glutamatergic excitatory postsynaptic currents (EPSCs) were remarkably suppressed in Corti.Pups compared to normal rat pups. Incomplete LTP and weaker EPSCs in Corti.Pups were attributed to the delayed postsynaptic development of CA1 neurons, showing a higher expression of NR2B subunits and lower expression of PSD-95 and BDNF. These results indicated that the prenatal treatment with corticosterone to elevate cortisol level might potently downregulate the BDNF-mediated signaling critical for the synaptic development of hippocampal CA1 neurons during brain development, and subsequently, induce learning and memory impairment. Our findings suggest a possibility that the prenatal dysregulation of cortisol triggers the epigenetic pathogenesis of neurodevelopmental psychiatric disorders, such as ADHD and autism.

Effects of clitorienolactones from Clitoria ternatea root on calcium channel mediating hippocampal long-term potentiation in rats induced chronic cerebral hypoperfusion.

Chronic cerebral hypoperfusion (CCH) is a common mechanism of acute brain injury due to impairment of blood flow to the brain. Moreover, a prolonged lack of oxygen supply may result in cerebral infarction or global ischemia, which subsequently causes long-term memory impairment. Research on using Clitoria ternatea root extract for treating long-term memory has been studied extensively. However, the bioactive compound contributing to its neuroprotective effects remains uncertain. In the present study, we investigate the effects of clitorienolactone A (CLA) and B (CLB) from the roots of Clitoria ternatea extract on hippocampal neuroplasticity in rats induced by CCH. CLA and CLB were obtained using column chromatography. The rat model of CCH was induced using two-vessel occlusion surgery (2VO). The 2VO rats were given 10 mg/kg of CLA and CLB orally, followed by hippocampal neuroplasticity recording using in vivo electrophysiological. Rats received CLA and CLB (10 mg/kg) significantly reversed the impairment of long-term potentiation following 2VO surgery. Furthermore, we investigate the effect of CLA and CLB on the calcium channel using the calcium imaging technique. During hypoxia, CLA and CLB sustain the increase in intracellular calcium levels. We next predict the binding interactions of CLA and CLB against NMDA receptors containing GluN2A and GluN2B subunits using in silico molecular docking. Our result found that both CLA and CLB exhibited lower binding affinity against GluN2A and GluN2B subunits. Our findings demonstrated that bioactive compounds from Clitoria ternatea improved long-term memory deficits in the chronic cerebral hypoperfusion rat model via calcium uptake. Hence, CLA and CLB could be potential therapeutic tools for treating cognitive dysfunction.

Impact of enriched environment on motor performance and learning in mice.

Neuroscience heavily relies on animal welfare in laboratory rodents as it can significantly affect brain development, cognitive function and memory formation. Unfortunately, laboratory animals are often raised in artificial environments devoid of physical and social stimuli, potentially leading to biased outcomes in behavioural assays. To assess this effect, we examined the impact of social and physical cage enrichment on various forms of motor coordination. Our findings indicate that while enriched-housed animals did not exhibit faster learning in eyeblink conditioning, the peak timing of their conditioned responses was slightly, but significantly, improved. Additionally, enriched-housed animals outperformed animals that were housed in standard conditions in the accelerating rotarod and ErasmusLadder test. In contrast, we found no significant effect of enrichment on the balance beam and grip strength test. Overall, our data suggest that an enriched environment can improve motor performance and motor learning under challenging and/or novel circumstances, possibly reflecting an altered state of anxiety.

Bright daylight produces negative effects on affective and cognitive outcomes in nocturnal rats.

The daily light/dark cycle affects animals' learning, memory, and cognition. Exposure to insufficient daylight illumination negatively impacts emotion and cognition, leading to seasonal affective disorder characterized by depression, anxiety, low motivation, and cognitive impairment in diurnal animals. However, how this affects memory, learning, and cognition in nocturnal rodents is largely unknown. Here, we studied the effect of daytime light illuminance on memory, learning, cognition, and expression of mRNA levels in the hippocampus, thalamus, and cortex, the higher-order learning centers. Two experiments were performed. In experiment one, rats were exposed to 12 L:12D (12 h light and 12 h dark) with a 10, 100, or 1000 lx daytime light illuminance. After 30 days, various behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, and passive avoidance test) were performed. In experiment 2, rats since birth were raised either under constant bright light (250 lx; LL) or a daily light-dark cycle (12 L:12D). After four months, behavioral tests (novel object recognition test, hole board test, elevated plus maze test, radial arm maze, passive avoidance test, Morris water maze, and Y-maze tests) were performed. At the end of experiments, rats were sampled, and mRNA expression of Brain-Derived Neurotrophic Factor (Bdnf), Tyrosine kinase (Trk), microRNA132 (miR132), Neurogranin (Ng), Growth Associated Protein 43 (Gap-43), cAMP Response Element-Binding Protein (Crebp), Glycogen synthase kinase-3ß (Gsk3ß), and Tumour necrosis factor-α (Tnf-α) were measured in the hippocampus, cortex, and thalamus of individual rats. Our results show that exposure to bright daylight (100 and 1000 lx; experiment 1) or constant light (experiment 2) compromises memory, learning, and cognition. Suppressed expression levels of these mRNA were also observed in the hypothalamus, cortex, and thalamus. These results suggest that light affects differently to different groups of animals.

Elevated Plus Maze for Assessment of Anxiety and Memory in Rodents.

The elevated plus maze is the most widely used paradigm to evaluate anxiety-associated behavioral alterations in rodent models of central nervous system (CNS) disorders. Unconditioned aversive behavior for open and elevated areas is a measure of anxiety and can be assessed by the plus maze. Plus maze consists of perpendicularly arranged open arms and closed arms crossed in the middle with a central platform. Rodents are allowed to explore the maze between the open and closed arms. The number of entries and time spent in the open arms and the closed arms are used as indicators for the anxiety nature of the animals. Transfer latency is a memory indicator that measures the amount of time it takes to move an animal from an open arm to a closed arm. This chapter describes the pretest conditions, materials required, and protocol for the conductance and evaluating the results for the anxiety and cognition-related behavior in rodents.

Effects of schisandrin B on hypoxia-related cognitive function and protein expression in vascular dementia rats.

Vascular dementia (VD) a heterogenous group of brain disorders in which cognitive impairment is attributable to vascular risk factors and cerebrovascular disease. A common phenomenon in VD is a dysfunctional cerebral regulatory mechanism associated with insufficient cerebral blood flow, ischemia and hypoxia. Under hypoxic conditions oxygen supply to the brain results in neuronal death leading to neurodegenerative diseases including Alzheimer's (AD) and VD. In conditions of hypoxia and low oxygen perfusion, expression of hypoxia-inducible factor 1 alpha (HIF-1α) increases under conditions of low oxygen and low perfusion associated with upregulation of expression of hypoxia-upregulated mitochondrial movement regulator (HUMMR), which promotes anterograde mitochondrial transport by binding with trafficking protein kinesin 2 (TRAK2). Schisandrin B (Sch B) an active component derived from Chinese herb Wuweizi prevented ß-amyloid protein induced morphological alterations and cell death using a SH-SY5Y neuronal cells considered an AD model. It was thus of interest to determine whether Sch B might also alleviate VD using a rat bilateral common carotid artery occlusion (BCAO) dementia model. The aim of this study was to examine the effects of Sch B in BCAO on cognitive functions such as Morris water maze test and underlying mechanisms involving expression of HIF-1α, TRAK2, and HUMMR levels. The results showed that Sch B improved learning and memory function of rats with VD and exerted a protective effect on the hippocampus by inhibition of protein expression of HIF-1α, TRAK2, and HUMMR factors. Evidence indicates that Sch B may be considered as an alternative in VD treatment.

The combination treatment of hypothermia and intranasal insulin ameliorates the structural and functional changes in a rat model of traumatic brain injury.

The present study aimed to investigate the combination effects of hypothermia (HT) and intranasal insulin (INS) on structural changes of the hippocampus and cognitive impairments in the traumatic brain injury (TBI) rat model. The rats were divided randomly into the following five groups (n = 10): Sham, TBI, TBI with HT treatment for 3 h (TBI + HT), TBI with INS (ten microliters of insulin) treatment daily for 7 days (TBI + INS), and TBI with combining HT and INS (TBI + HT + INS). At the end of the 7th day, the open field and the Morris water maze tests were done for evaluation of anxiety-like behavior and memory performance. Then, after sacrificing, the brain was removed for stereological study. TBI led to an increase in the total volume of hippocampal subfields CA1 and DG and a decrease in the total number of neurons and non-neuronal cells in both sub-regions, which was associated with anxiety-like behavior and memory impairment. Although, the combination of HT and INS prevented the increased hippocampal volume and cell loss and improved behavioral performances in the TBI group. Our study suggests that the combined treatment of HT and INS could prevent increased hippocampal volume and cell loss in CA1 and DG sub-regions and consequently improve anxiety-like behaviors and memory impairment following TBI.

Overexpression of MTMR14 induced learning and memory impairments in 2-month-old C57 mice.

Multiple biological functions of MTMR14 including regulation of autophagy, inflammation and Ca2+ homeostasis have been reported. However, its functional contribution to learning and memory remains unclear. In this study, we investigated whether upregulation of MTMR14 induced cognitive impairment and the underlying mechanisms. MTMR14 level was significantly increased in cells or brain tissues that overexpressed P301S-tau. The fusion of autophagosome and lysosome was significantly inhibited by overexpression of MTMR14 or P301S-tau. Upregulation of MTMR14 led to cognitive impairments in 2-month-old mice by inhibiting synaptic protein expression. These findings suggest that MTMR14 may be a key risk factor for cognitive ability.

Ameliorative Role of Mitochondrial Therapy in Cognitive Function of Vascular Dementia Mice.

BACKGROUND: Mitochondrial dysfunction plays a vital role in the progression of vascular dementia (VaD). We hypothesized that transfer of exogenous mitochondria might be a beneficial strategy for VaD treatment. OBJECTIVE: The study was aimed to investigate the role of mitochondrial therapy in cognitive function of VaD. METHODS: The activity and integrity of isolated mitochondria were detected using MitoTracker and Janus Green B staining assays. After VaD mice were intravenously injected with exogenous mitochondria, Morris water maze and passive avoidance tests were used to detect cognitive function of VaD mice. Haematoxylin and eosin, Nissl, TUNEL, and Golgi staining assays were utilized to measure neuronal and synaptic injury in the hippocampus of VaD mice. Detection kits were performed to detect mitochondrial membrane potential (ΔΨ), SOD activity and the levels of ATP, ROS, and MDA in the brains of VaD mice. RESULTS: The results showed that isolated mitochondria were intact and active. Mitochondrial therapy could ameliorate cognitive performance of VaD mice. Additionally, mitochondrial administration could attenuate hippocampal neuronal and synaptic injury, improve mitochondrial ΔΨ, ATP level and SOD activity, and reduce ROS and MDA levels in the brains of VaD mice. CONCLUSIONS: The study reports profitable effect of mitochondrial therapy against cognitive impairment of VaD, making mitochondrial treatment become a promising therapeutic strategy for VaD.

Gene knockout of RNA binding motif 5 in the brain alters RIMS2 protein homeostasis in the cerebellum and Hippocampus and exacerbates behavioral deficits after a TBI in mice.

RNA binding motif 5 (RBM5) is a tumor suppressor in cancer but its role in the brain is unclear. We used conditional gene knockout (KO) mice to test if RBM5 inhibition in the brain affects chronic cortical brain tissue survival or function after a controlled cortical impact (CCI) traumatic brain injury (TBI). RBM5 KO decreased baseline contralateral hemispheric volume (p < 0.0001) and exacerbated ipsilateral tissue loss at 21 d after CCI in male mice vs. wild type (WT) (p = 0.0019). CCI injury, but not RBM5 KO, impaired beam balance performance (0-5d post-injury) and swim speed on the Morris Water Maze (MWM) (19-20d) (p < 0.0001). RBM5 KO was associated with mild learning impairment in female mice (p = 0.0426), reflected as a modest increase in escape latency early in training (14-18d post-injury). However, KO did not affect spatial memory at 19d post-injury in male or in female mice but it was impaired by CCI in females (p = 0.0061). RBM5 KO was associated with impaired visual function in male mice on the visible platform test at 20d post-injury (p = 0.0256). To explore signaling disturbances in KOs related to behavior, we first cross-referenced known brain-specific RBM5-regulated gene targets with genes in the curated RetNet database that impact vision. We then performed a secondary literature search on RBM5-regulated genes with a putative role in hippocampal function. Regulating synaptic membrane exocytosis 2 (RIMS) 2 was identified as a gene of interest because it regulates both vision and hippocampal function. Immunoprecipitation and western blot confirmed protein expression of a novel ~170 kDa RIMS2 variant in the cerebellum, and in the hippocampus, it was significantly increased in KO vs WT (p < 0.0001), and in a sex-dependent manner (p = 0.0390). Furthermore, male KOs had decreased total canonical RIMS2 levels in the cerebellum (p = 0.0027) and hippocampus (p < 0.0001), whereas female KOs had increased total RIMS1 levels in the cerebellum (p = 0.0389). In summary, RBM5 modulates brain function in mammals. Future work is needed to test if RBM5 dependent regulation of RIMS2 splicing effects vision and cognition, and to verify potential sex differences on behavior in a larger cohort of mice.

Neonatal olfactory bulbectomy causes dendritic spine retraction in dorsal hippocampal CA3 neurons in female rats and spatial learning deficits in male rats.

Olfactory bulbectomy (OBX) is an experimental strategy that is widely employed because it produces changes at different levels (from behavioral to molecular) that can be related to symptoms of depression in humans. This procedure has been widely studied in adult rats, but little information has been obtained of its effect in neonatal rats. The objective of the present study was to evaluate learning and memory capacity and dendritic spine density in dorsal hippocampal CA3 neurons. Seven-day-old male and female Wistar rats were subjected to nOBX by suction, we included an intact group as a control (CON) and a sham-operated group (SHAM), too. Spatial learning and memory were measured at 56 days of age using a Morris water maze. A different cohort of experimental groups was used to measure dendritic spine density by Golgi-Cox impregnation. Male rats with nOBX showed a pronounced spatial learning deficit than female rats. Also, there was a significant decrease in basilar dendritic spine density in female rats with nOBX compared to the CON group. No changes were observed in this variable in male rats with nOBX. Our results allow us to suggest that there is sexual dimorphism in the effect of nOBX on the dorsal hippocampus and its relationship with spatial learning and memory processes.

Early Life Stress Negatively Impacts Spatial Learning Acquisition and Increases Hippocampal CA1 Microglial Activation After a Mild Traumatic Brain Injury in Adult Male Rats.

Early life stress (ELS) affects neurogenesis and spatial learning, and increases neuroinflammation after a pediatric mild traumatic brain injury (mTBI). Previous studies have shown that ELS has minimal effects in juveniles but shows age-dependent effects in adults. Hence, we aimed to evaluate the effects of ELS in adult male rats after an mTBI. Maternal separation for 180 min per day (MS180) during the first 21 post-natal (P) days was used as the ELS model. At P110, the rats were subjected to a mild controlled cortical impact injury (2.6 mm) or sham surgery. Spatial learning was evaluated in the Morris water maze (MWM) 14 days after surgery and both microglial activation and neurogenesis were quantified. The results indicate that MS180 + mTBI, but not control (CONT) + mTBI, rats show deficiencies in the acquisition of spatial learning. mTBI led to comparable increases in microglial activation in both the hilus and cortical regions for both groups. However, MS180 + mTBI rats exhibited a greater increase in microglial activation in the ipsilateral CA1 hippocampus subfield compared with CONT + mTBI. Interestingly, for the contralateral CA1 region, this effect was observed exclusively in MS180 + mTBI. ELS and mTBI independently caused a decrease in hippocampal neurogenesis and this effect was not increased further in MS180 + mTBI rats. The findings demonstrate that ELS and mTBI synergistically affect cognitive performance and neuroinflammation, thus supporting the hypothesis that increased inflammation resulting from the combination of ELS and mTBI could underlie the observed effects on learning.

The administration of rhBmal1 reduces sleep deprivation-induced anxiety and cognitive impairment in mice.

BACKGROUND: In mammals, circadian rhythms control metabolism, immunological response and reproductive processes. Bmal1 (brain and muscle Arnt-like protein-1) is a key element in the regulation of circadian rhythms. METHODS: This investigation explores the pathophysiological effects of sleep deprivation in a mouse model as well as the potential underlying mechanisms. A mouse sleep deprivation model was constructed using a modified multi-platform water environment method. The anxiety-like behaviours of mice were assessed by the open field test and elevated plus maze, and the cognitive function of mice was tested by the nest-building test. The expression levels of targeted genes were determined by Western blotting assay and RT-qPCR assay. RESULTS: We found that sleep deprivation profoundly enhanced anxiety levels and impaired cognitive function in mice. Sleep deprivation also reduced the expression levels of Bmal1 and BDNF (brain-derived neurotrophic factor) and increased oxidative stress in the hippocampus of mice. The intraperitoneal injection of human recombinant rhBmal1 protein alleviated sleep deprivation-induced anxiety and cognitive impairment, restored Bmal1 and BDNF levels, and reduced oxidative stress in the hippocampus of mice. CONCLUSIONS: rhBmal1 treatment might serve as a potential therapy for mitigating sleep deprivation-related unfavourable symptoms.

The role of environmental contextual cues in sequence learning: evidence from a virtual maze context.

Studies on sequence learning usually focus on single, isolated stimuli that are presented sequentially. For example, in the serial reaction time (RT) task, stimuli are either presented in a predictable sequence or in a random sequence, and better performance with the predictable sequence is taken as evidence for sequence-specific learning. Yet, little is known about the role of environmental context cues in sequence learning. If the target stimuli are embedded in a meaningful context, would this facilitate learning by providing helpful contextual associations or would it hinder learning by adding distracting stimuli? This question was examined in two studies. A pilot study compared sequence learning in a virtual maze with a horizontal vs. vertical maze context, in which arrow stimuli guide spatial lever movement responses that resulted in a corresponding virtual transport on the screen. The results showed only overall somewhat better performance with the vertical maze compared to the horizontal maze, but general practice effects and sequence-specific learning effects were the same for both contexts. The main study compared sequence learning with a maze context to sequence learning of arrows without a maze context. The results showed significantly better learning with maze context than without context. These data suggest that the maze context facilitated sequence learning by inducing a meaningful spatial representation ("mental map") similar to that formed in wayfinding.

Object-place-context learning impairment correlates with spatial learning impairment in aged Long-Evans rats.

The hippocampal formation is vulnerable to the process of normal aging. In humans, the extent of this age-related deterioration varies among individuals. Long-Evans rats replicate these individual differences as they age, and therefore they serve as a valuable model system to study aging in the absence of neurodegenerative diseases. In the Morris water maze, aged memory-unimpaired (AU) rats navigate to remembered goal locations as effectively as young rats and demonstrate minimal alterations in physiological markers of synaptic plasticity, whereas aged memory-impaired (AI) rats show impairments in both spatial navigation skills and cellular and molecular markers of plasticity. The present study investigates whether another cognitive domain is affected similarly to navigation in aged Long-Evans rats. We tested the ability of young, AU, and AI animals to recognize novel object-place-context (OPC) configurations and found that performance on the novel OPC recognition paradigm was significantly correlated with performance on the Morris water maze. In the first OPC test, young and AU rats, but not AI rats, successfully recognized and preferentially explored objects in novel OPC configurations. In a second test with new OPC configurations, all age groups showed similar OPC associative recognition memory. The results demonstrated similarities in the behavioral expression of associative, episodic-like memory between young and AU rats and revealed age-related, individual differences in functional decline in both navigation and episodic-like memory abilities.

Sex-specific variations in spatial reference memory acquisition: Insights from a comprehensive behavioral test battery in C57BL/6JRj mice.

Sex differences in declarative memory are described in humans, revealing a female or a male advantage depending on the task. Specifically, spatial memory (i.e., spatial navigation) is typically most efficient in men. This sexual dimorphism has been replicated in male rats but not clearly in mice. In this study, sex differences in spatial memory were assessed in thirty-six C57BL/6 J mice (Janvier Labs; i.e., C57BL/6JRj mice), a widely used mouse substrain. Both male and female mice (12 weeks-old) were subjected to standard behavioral paradigms: the elevated plus maze, the open field test, the novel object and place tests, the forced swimming test, and the water maze test for spatial navigation. Across assessment, no sex differences were found in measures of locomotor activity, emotional and behavioral responses, and object and place recognition memories. In the water maze, male mice were faster in learning the platform location in the reference memory training and used more spatial strategies during the first training days. However, both sexes reached a similar asymptotic performance and performed similarly in the probe trial for long-term memory consolidation. No sex differences were found in the cued training, platform inversion sessions, or spatial working memory sessions. Hippocampal expression of the brain-derived neurotrophic factor was similar in both sexes, either in basal conditions or after performing the behavioral training battery. Importantly, female mice were not more variable than males in any measure analyzed. This outcome encourages the investigation of sex differences in animal models and the usefulness of including female mice in behavioral research.

A bridge to recovery: Acute amantadine prior to environmental enrichment after brain trauma augments cognitive benefit.

Environmental enrichment (EE) facilitates motor and cognitive recovery after traumatic brain injury (TBI). Historically, EE has been provided immediately and continuously after TBI, but this paradigm does not model the clinic where rehabilitation is typically not initiated until after critical care. Yet, treating TBI early may facilitate recovery. Hence, we sought to provide amantadine (AMT) as a bridge therapy before commencing EE. It was hypothesized that bridging EE with AMT would augment motor and cognitive benefits. Anesthetized adult male rats received a cortical impact (2.8 mm deformation at 4 m/s) or sham surgery and then were housed in standard (STD) conditions where they received intraperitoneal AMT (10 mg/kg or 20 mg/kg) or saline vehicle (VEH; 1 mL/kg) beginning 24 h after surgery and once daily during the 6-day bridge phase or once daily for 19 days for the non-bridge groups (i.e., continuously STD-housed) to compare the effects of acute AMT plus EE vs. chronic AMT alone. Abbreviated EE, which was presented to closer emulate clinical rehabilitation (e.g., 6 h/day), began on day 7 for the AMT bridge and chronic EE groups. Motor (beam-walking) and cognition (acquisition of spatial learning and memory) were assessed on days 7-11 and 14-19, respectively. Cortical lesion volume and hippocampal cell survival were quantified on day 21. EE, whether provided in combination with VEH or AMT, and AMT (20 mg/kg) + STD, benefitted motor and cognition vs. the STD-housed VEH and AMT (10 mg/kg) groups (p < 0.05). The AMT (20 mg/kg) + EE group performed better than the VEH + EE, AMT (10 mg/kg) + EE, and AMT (20 mg/kg) + STD groups in the acquisition of spatial learning (p < 0.05) but did not differ in motor function (p > 0.05). All groups receiving EE exhibited decreased cortical lesion volumes and increased CA3 neuron survival relative to the STD-housed groups (p < 0.05) but did not differ from one another (p > 0.05). The added cognitive benefit achieved by bridging EE with AMT (20 mg/kg) supports the hypothesis that the temporal separation of combinational therapies is more effective after TBI.

Circuit mechanisms of navigation strategy learning in mice.

Navigation tasks involve the gradual selection and deployment of increasingly effective searching procedures to reach targets. The brain mechanisms underlying such complex behavior are poorly understood, but their elucidation might provide insights into the systems linking exploration and decision making in complex learning. Here, we developed a trial-by-trial goal-related search strategy analysis as mice learned to navigate identical water mazes encompassing distinct goal-related rules and monitored the strategy deployment process throughout learning. We found that navigation learning involved the following three distinct phases: an early phase during which maze-specific search strategies are deployed in a minority of trials, a second phase of preferential increasing deployment of one search strategy, and a final phase of increasing commitment to this strategy only. The three maze learning phases were affected differently by inhibition of retrosplenial cortex (RSC), dorsomedial striatum (DMS), or dorsolateral striatum (DLS). Through brain region-specific inactivation experiments and gain-of-function experiments involving activation of learning-related cFos+ ensembles, we unraveled how goal-related strategy selection relates to deployment throughout these sequential processes. We found that RSC is critically important for search strategy selection, DMS mediates strategy deployment, and DLS ensures searching consistency throughout maze learning. Notably, activation of specific learning-related ensembles was sufficient to direct strategy selection (RSC) or strategy deployment (DMS) in a different maze. Our results establish a goal-related search strategy deployment approach to dissect unsupervised navigation learning processes and suggest that effective searching in navigation involves evidence-based goal-related strategy direction by RSC, reinforcement-modulated strategy deployment through DMS, and online guidance through DLS.

Environmental enrichment improves cognitive function, learning, memory and anxiety-related behaviours in rodent models of dementia: Implications for future study.

Environmental enrichment (EE) is a process of brain stimulation by modifying the surroundings, for example, by changing the sensory, social, or physical conditions. Rodents have been used in such experimental strategies through exposure to diverse physical, social, and exploration conditions. The present study conducted an extensive analysis of the existing literature surrounding the impact of EE on dementia rodent models. The review emphasised the two principal aspects that are very closely related to dementia: cognitive function (learning and memory) as well as psychological factors (anxiety-related behaviours such as phobias and unrealistic worries). Also highlighted were the mechanisms involved in the rodent models of dementia showing EE effects. Two search engines, PubMed and Science Direct, were used for data collection using the following keywords: environmental enrichment, dementia, rodent model, cognitive performance, and anxiety-related behaviour. Fifty-five articles were chosen depending on the criteria for inclusion and exclusion. The rodent models with dementia demonstrated improved learning and memory in the form of hampered inflammatory responses, enhanced neuronal plasticity, and sustained neuronal activity. EE housing also prevented memory impairment through the prevention of amyloid beta (Aß) seeding formation, an early stage of Aß plaque formation. The rodents subjected to EE were observed to present increased exploratory activity and exert less anxiety-related behaviour, compared to those in standard housing. However, some studies have proposed that EE intervention through exercise would be too mild to counteract the anxiety-related behaviour and risk assessment behaviour deficits in the Alzheimer's disease rodent model. Future studies should be conducted on old-aged rodents and the duration of EE exposure that would elicit the greatest benefits since the existing studies have been conducted on a range of ages and EE durations. In summary, EE had a considerable effect on dementia rodent models, with the most evident being improved cognitive function.

SynCAM1 deficiency in the hippocampal parvalbumin interneurons contributes to sevoflurane-induced cognitive impairment in neonatal rats.

AIMS: Sevoflurane is widely used for general anesthesia in children. Previous studies reported that multiple neonatal exposures to sevoflurane can induce long-term cognitive impairment in adolescent rats, but the underlying mechanisms were not defined. METHODS: Postnatal day 6 (P6) to P8 rat pups were exposed to 30% oxygen with or without 3% sevoflurane balanced with air. The Y maze test (YMT) and Morris water maze (MWM) tests were performed in some cohorts from age P35 to assess cognitive functions, and their brain samples were harvested at age P14, 21, 28, 35, and 42 for measurements of various molecular entities and in vivo electrophysiology experiments at age P35. RESULTS: Sevoflurane exposure resulted in cognitive impairment that was associated with decreased synCAM1 expression in parvalbumin (PV) interneurons, a reduction of PV phenotype, disturbed gamma oscillations, and dendritic spine loss in the hippocampal CA3 region. Enriched environment (EE) increased synCAM1 expression in the PV interneurons and attenuated sevoflurane-induced cognitive impairment. The synCAM1 overexpression by the adeno-associated virus vector in the hippocampal CA3 region restored sevoflurane-induced cognitive impairment, PV phenotype loss, gamma oscillations decrease, and dendritic spine loss. CONCLUSION: Our data suggested that neonatal sevoflurane exposure results in cognitive impairment through decreased synCAM1 expression in PV interneurons in the hippocampus.