Serotonin-1A receptor activation in the median raphe nucleus improves response learning-based strategy in 192IgG saporin-induced cognitive impairments.

Deficits in the translation between egocentric-allocentric strategies may become another diagnostic mark for neurodegenerative disorders, especially Alzheimer's disease. Regarding the specific regional distribution of serotonin-1A receptor in brain areas mediating allocentric (externally-centered) spatial navigation to the escape location, here we studied the effects of median raphe nucleus serotonin-1A autoreceptors stimulation, [8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT); 4 µg/0.5 µl saline], of a selective cholinergic denervation by intracerebroventricular administration of the 192IgG saporin (1µl/each ventricle), on male Wistar rats search strategies in a Morris maze during acquisition, and before probe sessions. Despite some evidence of spatial hippocampal dependent knowledge to those PBS/Saline animals, their performance dropped to chance levels on probe trial. Therefore, we considered two probabilities and first analyzed the ability of the rats to make better use of one or more strategies. We showed statistically significant increases in the distances associated with egocentric (body-centered) non-spatial strategies, random searching in particular, in 192IgG/8OH rats, which led to their improved performance. Second, considering to what extent a shift in search strategy use improves performance indicated that 8-OH-DPAT alone did not affect learning since it appeared the related performance was impaired over days. However, the strategy choices made by 192IgG/8OH rats increased performance by more than 12% compared to 192IgG/Saline rats, an effect reversed with pre-treatment by serotonin-1A receptor antagonist, N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane-carboxamide (WAY 100635). The results strongly suggest the potential role of serotonergic system, via the serotonin-1A receptors, in spatial navigation. We argue that the receptors are of interest as therapeutic targets that can be used against age-related cognitive decline.

Exposure to 3'Sialyllactose-Poor Milk during Lactation Impairs Cognitive Capabilities in Adulthood.

Breast milk exerts pivotal regulatory functions early in development whereby it contributes to the maturation of brain and associated cognitive functions. However, the specific components of maternal milk mediating this process have remained elusive. Sialylated human milk oligosaccharides (HMOs) represent likely candidates since they constitute the principal neonatal dietary source of sialic acid, which is crucial for brain development and neuronal patterning. We hypothesize that the selective neonatal lactational deprivation of a specific sialylated HMOs, sialyl(alpha2,3)lactose (3'SL), may impair cognitive capabilities (attention, cognitive flexibility, and memory) in adulthood in a preclinical model. To operationalize this hypothesis, we cross-fostered wild-type (WT) mouse pups to B6.129-St3gal4tm1.1Jxm/J dams, knock-out (KO) for the gene synthesizing 3'SL, thereby providing milk with approximately 80% 3'SL content reduction. We thus exposed lactating WT pups to a selective reduction of 3'SL and investigated multiple cognitive domains (including memory and attention) in adulthood. Furthermore, to account for the underlying electrophysiological correlates, we investigated hippocampal long-term potentiation (LTP). Neonatal access to 3'SL-poor milk resulted in decreased attention, spatial and working memory, and altered LTP compared to the control group. These results support the hypothesis that early-life dietary sialylated HMOs exert a long-lasting role in the development of cognitive functions.

Issues in the design, analysis, and application of rodent developmental neurotoxicology studies.

Developmental neurotoxicity (DNT) studies could benefit from revisions to study design, data analysis, and some behavioral test methods to enhance reproducibility. The Environmental Protection Agency (EPA) reviewed 69 studies submitted to the Office of Pesticide Programs. Two of the behavioral tests identified the lowest observable adverse effect level (LOAEL) 20 and 13 times, respectively, while the other two tests identified the LOAEL only 3 and 4 times, respectively. The EPA review showed that the functional observational battery (FOB) was least effective at detecting the LOAEL, whereas tests of learning and memory (L&M) had methodological shortcomings. Human neurodevelopmental toxicity studies over the past 30 years show that most of the adverse effects are on higher cognitive functions such as L&M. The results of human studies together with structure-function relationships from neuroscience, suggest that tests of working memory, spatial navigation/memory, and egocentric navigation/memory should be added to guideline studies. Collectively, the above suggest that EPA and EU DNT studies would better reflect human findings and be more relevant to children by aligning L&M tests to the same domains that are affected in children, removing less useful methods (FOB), and using newer statistical models to better account for random factors of litter and litter × sex. Common issues in study design and data analyses are discussed: sample size, random group assignment, blinding, elimination of subjective rating methods, avoiding confirmation bias, more complete reporting of species, housing, test protocols, age, test order, and litter effects. Litter in DNT studies should at least be included as a random factor in ANOVA models and may benefit from inclusion of litter × sex as random factors.

Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats.

Adolescent chronic stress has been shown to induce functional, biochemical and morphological modifications of the hippocampus, leading to stress-related disorders in adulthood. The present study investigated the effects of exercise, crocin and their combination on spatial learning and memory impairment and dendritic retraction of the CA3 pyramidal neurons induced by chronic adolescent stress in adult male rats. Rats were exposed to restraint stress 2 h/day for 10 days during postnatal days (PNDs) 30-40. Following this period, separate groups of animals were treated with crocin (25 and 50 mg/kg), exposed to running wheel, and or received the combined treatment during PNDs 41-55. Following the interventions, plasma levels of corticosterone, spatial learning and memory, apical dendritic length of CA3 pyramidal neurons and BDNF levels in the CA3 area were assessed. Findings showed that adolescent stress significantly increased corticosterone levels and caused a tendency to reduce CA3 BDNF levels. Adolescent stress also impaired spatial learning and memory, and retracted apical dendritic length of CA3 pyramidal neurons. Crocin, voluntary exercise, and their combination recovered stress-induced spatial learning and impairment and CA3 pyramidal neurons dendritic length retraction. All treatments also reduced significantly corticosterone levels and enhanced CA3 BDNF levels in the stress groups. Finally, these treatments even increased apical dendritic length of CA3 pyramidal neurons in the non-stress groups. These findings indicate that detrimental effects of adolescent stress on cognitive function and hippocampal morphology in adulthood could be restored by early interventions with physical activity and crocin treatment during adolescent period.

N-Acetylcysteine Attenuates the Anxiety-Like Behavior and Spatial Cognition Impairment Induced by Doxorubicin and Cyclophosphamide Combination Treatment in Rats.

BACKGROUND: Cancer patients can suffer from psychological and cognitive disorders after chemotherapy, which influence quality of life. OBJECTIVE: Oxidative stress may contribute to the psychological and cognitive disorders induced in rats by chemotherapy. In the present study, we examined the effects of N-acetylcysteine, an anti-oxidant, on anxiety-like behavior and cognitive impairment in rats treated with a combination of doxorubicin and cyclophosphamide. METHODS: Rats were intraperitoneally injected with doxorubicin and cyclophosphamide once a week for 2 weeks. The light-dark test and the novel location recognition test were used to assess anxiety-like behavior and spatial cognition, respectively. The rats' hippocampal levels of glutathione (GSH) and glutathione disulfide (GSSG) were measured using a GSSG/GSH quantification kit. RESULTS: Combined treatment with doxorubicin and cyclophosphamide produced anxiety-like behavior and cognitive impairment in rats. N-acetylcysteine reversed the anxiety-like behavior and inhibition of novel location recognition induced by the combination treatment. Furthermore, the combination of doxorubicin and cyclophosphamide significantly reduced the rats' hippocampal GSH/GSSG ratios. N-acetylcysteine reversed the reduction in the GSH/GSSG ratio seen in the doxorubicin and cyclophosphamide-treated rats. CONCLUSION: These results suggest that N-acetylcysteine inhibits doxorubicin and cyclophosphamide-induced anxiety-like behavior and cognitive impairment by reducing oxidative stress in the hippocampus.

Agonism of Histaminergic-H1 Receptors in Ischemic Postconditioning During Cerebral Ischemia-Reperfusion Injury is Protective.

BACKGROUND: Stroke is associated with cerebral ischemia/reperfusion (I/R) injury. Ischemic postconditioning (IPoC) reduces cerebral ischemic injury in rats and offers neuroprotection. The central histaminergic pathway possesses a crucial role in the pathogenesis of cerebral I/R, but its neuroprotective role in IPoC is still unidentified. OBJECTIVE: This research explored the role of the histaminergic in IPoC during cerebral I/R injury in the rat. METHODS: Global cerebral ischemia/reperfusion (GCI/R) injury in Wistar albino rats was induced by occluding the bilateral carotid arteries for 10 minutes, followed by reperfusion. IPoC was provided by giving three episodes of I/R post GCI (10 min), after which of reperfusion was permitted. Inclined- beam-walk, hanging-wire, lateral-push, and rota-rod tests were employed to assess motor functions, and Morris water maze (MWM) was used to assess spatial learning as well as memory in animals. Cerebral oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione- GSH), inflammatory markers (myeloperoxidase-MPO), acetylcholinesterase activity- AChE, infarct size, and histopathological changes were also assessed. L-histidine and chlorpheniramine were used as histaminergic agonists and antagonists. RESULTS: I/R animals showed a reduction in memory and motor function, and an increase in cerebral oxidative stress, inflammation, AChE activity, infarct size and histopathological changes. Episodes of IPoC post-ischemia attenuated the deleterious effects of I/R injury. Pretreatment (30 min before cerebral ischemia) with L-histidine mimicked the neuroprotective effects of IPoC. However, neuroprotection produced by IPoC was abolished by pretreatment with chlorpheniramine (histaminergic- H1 receptor antagonist). CONCLUSION: IPoC may provide neuroprotection against cerebral I/R induced brain injury by modulating the histaminergic-H1-receptor pathway.

Neonicotinoids disrupt circadian rhythms and sleep in honey bees.

Honey bees are critical pollinators in ecosystems and agriculture, but their numbers have significantly declined. Declines in pollinator populations are thought to be due to multiple factors including habitat loss, climate change, increased vulnerability to disease and parasites, and pesticide use. Neonicotinoid pesticides are agonists of insect nicotinic cholinergic receptors, and sub-lethal exposures are linked to reduced honey bee hive survival. Honey bees are highly dependent on circadian clocks to regulate critical behaviors, such as foraging orientation and navigation, time-memory for food sources, sleep, and learning/memory processes. Because circadian clock neurons in insects receive light input through cholinergic signaling we tested for effects of neonicotinoids on honey bee circadian rhythms and sleep. Neonicotinoid ingestion by feeding over several days results in neonicotinoid accumulation in the bee brain, disrupts circadian rhythmicity in many individual bees, shifts the timing of behavioral circadian rhythms in bees that remain rhythmic, and impairs sleep. Neonicotinoids and light input act synergistically to disrupt bee circadian behavior, and neonicotinoids directly stimulate wake-promoting clock neurons in the fruit fly brain. Neonicotinoids disrupt honey bee circadian rhythms and sleep, likely by aberrant stimulation of clock neurons, to potentially impair honey bee navigation, time-memory, and social communication.

Influence of sex, menstrual cycle, and hormonal contraceptives on egocentric navigation with or without landmarks.

This study examines the influence of sex, menstrual cycle, hormonal contraceptives (HC) and sex hormone levels in following egocentric navigation instructions with or without landmarks. Estradiol seem to bias the reference frame for navigation during estrous cycle of female rats. However, previous studies in humans found no differences in overall navigation between women in their early follicular and mid-luteal menstrual cycle phases, whose performance was worse than that of men. Our study hypothesis was that the performance of women would be improved during the peri-ovulatory phase and would remain the same during placebo and active phases of HC users. The study included 21 men, 62 women with natural menstrual cycle (21 during early follicular phase, 20 during peri-ovulatory phase, and 21 during mid-luteal phase), and 38 women that were receiving HC (13 during placebo phase and 25 during active phase). The men outperformed the women with a natural menstrual cycle when following egocentric instructions without landmarks. However, the women's performance varied according to the phase of their menstrual cycle, differing from men during early follicular and mid-luteal phases but not during the peri-ovulatory phase. The use of HC also improved the performance of women to the extent that the difference with men disappeared. No differences were observed between HC-placebo and HC-active user groups during egocentric navigation without landmarks and among all groups during egocentric navigation with landmarks. Analysis of salivary hormones showed that testosterone levels were higher in men and that estradiol levels in women were higher during peri-ovulatory and mid-luteal phases and also in HC users. Progesterone levels were higher in women during the mid-luteal phase. These results appear compatible with beneficial effect of testosterone and estradiol on egocentric navigation without landmarks and with a block of this effect produced by progesterone.

Inactivation of the striatum in aged rats rescues their ability to learn a hippocampus-sensitive spatial navigation task.

Studies of age-related changes in learning and memory often focus on hippocampus-sensitive tasks and reveal age-associated impairments across numerous species and contexts. However, cognitive decline with advanced age is not all-encompassing; for example, forms of striatum-sensitive learning are conserved or enhanced with age. Under certain conditions, hippocampal and striatal memory systems function in opposition. In young adult rodents, disruption of one structure can enhance learning on tasks dependent on the other, suggesting that competitive interactions across memory systems contribute to learning and memory abilities. This report examines whether imbalances across memory systems might contribute to cognitive aging. We inactivated the striatum using central infusions of lidocaine (sodium channel blocker) prior to hippocampus-sensitive spatial (place) training in young (3-4-month-old) and old (24-25-month-old) F344 male rats. Consistent with prior work, vehicle-infused old rats exhibited place learning impairments relative to young rats. Additionally, striatal inactivation enhanced learning in old rats, but not young rats, abolishing the age-related impairment. These findings suggest that age-related declines in learning tasks thought to engage the hippocampus may stem from exaggerated interference from other memory systems and that interventions to target the striatum may reverse some age-related learning decrements.

Differential navigational strategies during spatial learning in a new modified version of the Oasis maze.

During spatial navigation, some typical parameters of learning have been observed, such as latency or path length. However, these parameters are sensitive to patterns of navigation and orientation that are not easily measurable. In the present study, we used a modified version of the Oasis maze and evaluated different parameters of learning, navigation, and orientation in different animal groups. Through a PCA (Principal component analysis) we found different factors such as learning, navigation, speediness, anxiety, orientation, path variability, and turning behavior. Each factor gathers different groups of behavioral variables. ANOVA analysis of those factors demonstrates that some of them are more strongly modulated by trial progression, while others by animal group differences, indicating that each group of variables is better reflecting one of these dimensions. To understand the nature of these navigation differences, we studied orientation strategies between animal conditions and across trials. We found that the main navigational strategy used by the animals consist of locating the target and directing their behaviors towards this area. When testing how this strategy changed after cognitive impairment or enhancement, we found that AßOs treated animals (Amyloid ß Oligomers, Alzheimer animal model) have strong orientation difficulties at locating the target at longer distances. While animals with learning enhancement (exercised rat) do not show changes in orientation behaviors. These analyses highlight that experimental manipulations affect learning, but also induced changes in the navigational strategies. We concluded that both dimensions can explain the differences observed in typical learning variables, such as latency or path length, motivating the development of new tools that asses this two-dimension as a separate but, interacting phenomenon.

Prolonged methamphetamine exposure during a critical period in neonatal Sprague Dawley rats does not exacerbate egocentric and allocentric learning deficits but increases reference memory impairments.

Children exposed to methamphetamine (MA) in utero have cognitive deficits. MA administration in rats for 5-10 days between postnatal days (P)6 and 20 produces cognitive deficits. The purpose of this study was to determine if extending MA administration by 5 days within P6-20 would exacerbate allocentric (Morris water maze) and egocentric (Cincinnati water maze) learning deficits. Sprague Dawley female and male offspring (split-litter design) were administered saline (SAL) or MA (10 mg/kg) four times daily from P6 to 20 to create four groups: (a) SAL from P6 to 20, (b) MA from P6 to 20 (MA6-20), (c) MA from P6 to 15 (MA6-15), or (d) MA from P11 to 20 (MA11-20); the latter groups received saline on days they did not receive MA. Egocentric, allocentric, and conditioned freezing tests began on P60. The MA6-15 and MA6-20 groups showed egocentric deficits, all MA groups had allocentric deficits but no differences in conditioned freezing compared with SAL controls. The MA6-15 and MA6-20 groups had similar deficits in learning and memory that were larger than in the MA11-20 group. Learning in both mazes was sex dependent, but no interactions with MA were found. The data demonstrate that extending the exposure period of MA beyond the sensitive periods (P6-15 and P11-20) did not exacerbate the cognitive deficits.

Place cell firing cannot support navigation without intact septal circuits.

Though it has been known for over half a century that interference with the normal activity of septohippocampal neurons can abolish hippocampal theta rhythmicity, a definitive answer to the question of its function has remained elusive. To clarify the role of septal circuits and theta in location-specific activity of place cells and spatial behavior, three drugs were delivered to the medial septum of rats: Tetracaine, a local anesthetic; muscimol, a GABA-A agonist; and gabazine, a GABA-A antagonist. All three drugs disrupted normal oscillatory activity in the hippocampus. However, tetracaine and muscimol both reduced spatial firing and interfered with the rat's ability to navigate to a hidden goal. After gabazine, location-specific firing was preserved in the absence of theta, but rats were unable to accurately locate the hidden goal. These results indicate that theta is unnecessary for location-specific firing of hippocampal cells, and that place cell activity cannot support accurate navigation when septal circuits are disrupted.

Spatial Navigation in Children and Young Adults with Fetal Alcohol Spectrum Disorders.

BACKGROUND: Rodent studies have consistently shown that prenatal alcohol exposure (PAE) impairs performance on the Morris water maze (MWM), a test of spatial navigation. A previous study comparing boys with fetal alcohol syndrome (FAS) to controls found poorer performance on the virtual water maze (VWM), a human analogue of the MWM. We examined PAE effects on virtual navigation in both sexes using the VWM in a moderately exposed Detroit cohort (N = 104; mean = 19.4 year) and a heavily exposed Cape Town, South African cohort (N = 62; mean = 10.4 year). METHODS: The task requires the participant to learn the location of a hidden platform in a virtual pool of water. The set of acquisition trials requires the participant to learn the location of the hidden platform and to return to that location repeatedly. The single-probe trial requires the participant to return to that location without knowing that the platform has been removed. RESULTS: No effects of FASD diagnostic group or PAE were detected on virtual navigation in the Detroit moderately exposed cohort. By contrast, in the more heavily exposed Cape Town cohort, the FAS/partial FAS (PFAS) group took longer to locate the hidden platform during acquisition than nonsyndromal heavily exposed (HE) and control groups, an effect that persisted even after controlling for IQ. Among boys, both the FAS/PFAS and HE groups performed more poorly than controls during acquisition, and both boys and girls born to women who binge drank performed more poorly than those born to abstainers/light drinkers. Both amount and frequency of PAE were related to poorer performance during the probe trial at 10 years of age. CONCLUSIONS: These data demonstrate deficits in spatial navigation among heavily exposed syndromal boys and girls and in nonsyndromal exposed boys.

The effects of developmental alcohol exposure on the neurobiology of spatial processing.

The consumption of alcohol during gestation is detrimental to the developing central nervous system. One functional outcome of this exposure is impaired spatial processing, defined as sensing and integrating information pertaining to spatial navigation and spatial memory. The hippocampus, entorhinal cortex, and anterior thalamus are brain regions implicated in spatial processing and are highly susceptible to the effects of developmental alcohol exposure. Some of the observed effects of alcohol on spatial processing may be attributed to changes at the synaptic to circuit level. In this review, we first describe the impact of developmental alcohol exposure on spatial behavior followed by a summary of the development of brain areas involved in spatial processing. We then provide an examination of the consequences of prenatal and early postnatal alcohol exposure in rodents on hippocampal, anterior thalamus, and entorhinal cortex-dependent spatial processing from the cellular to behavioral level. We conclude by highlighting several unanswered questions which may provide a framework for future investigation.

Protective effect of sakuranetin in brain cells of dementia model rats.

Alzheimer's disease (AD) is a high-incidence neurodegenerative disease with complex and diverse pathogenesis. With aging of the population and continuous improvement of living standards, the incidence of AD is on the increase. Therefore, there is need to develop more effective AD drugs in order to improve the quality of life of the elderly. Sakuranetin (SAK) is a dihydroflavonoid compound extracted from plants. It has many physiological properties. In this study, the effect of SAK on spatial discrimination in a rat model of cognitive dysfunction exposed to D-galactose was investigated with respect to its effect on malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) levels, and on the expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and nuclear factor-κB inhibitory factor-α (IκBα) in hippocampus of rats. The results obtained suggest that SAK may exert protective effects on brain cells through anti-oxidation mechanism. Moreover, the improvement in learning and memory impairment by SAK may also be related to the inhibition of inflammatory mediators in brain tissue. These findings provide scientific evidence that can be exploited for more effective treatment of Alzheimer's disease.

Identification of a Novel Peptide from ß-Casein That Enhances Spatial and Object Recognition Memory in Mice.

An increase in the aging population has spurred recent efforts to identify diet and lifestyle changes that help prevent cognitive decline. Several epidemiological investigations and clinical studies have indicated that consuming fermented dairy products prevents cognitive decline. Some peptides from whey including ß-lactolin improve memory impairment; the intake of Camembert cheese has been shown to prevent Alzheimer's in mouse models. To elucidate the molecular mechanisms underlying these preventive effects, we screened peptides from digested casein protein for their ability to improve spatial memory in a scopolamine-induced amnesia mouse model. Administration of KEMPFPKYPVEP peptide from ß-casein at 0.5 mg/kg (54.8 ± 2.5) and 2 mg/kg (57.9 ± 3.7) improved memory impairment in the amnesia mice in comparison with control (44.9 ± 3.4; p = 0.031 and p = 0.042, respectively) and increased dopamine (5.9 ± 3.8 [control] and 12.4 ± 6.2 [KEMPFPKYPVEP peptide]) and norepinephrine (7.7 ± 0.8 [control] and 9.9 ± 2.0 [KEMPFPKYPVEP peptide]) levels in the frontal cortex (p = 0.039 and p = 0.031, respectively). Collectively, our findings suggest that peptides in fermented dairy products prevent cognitive decline and support previously reported observations.

Relationships between drinking quantity and frequency and behavioral and hippocampal BOLD responses during working memory performance involving allocentric spatial navigation in college students.

BACKGROUND: Quantity and frequency of drinking may be used to effectively quantify the severity of alcohol-use. Drinking-severity has been related to neurocognitive impairments in such domains as spatial working memory (SWM). Youth drinking has been associated with altered neurofunctional underpinnings of SWM. The current study examined the relationship between drinking-severity and SWM processing. METHODS: One-hundred-and-seventy college drinkers reported the maximum number of drinks in a 24 -h period in the last six-months (quantity) and average number of drinking weeks in the last six-months (frequency). All participants performed a virtual Morris Water Task during fMRI which included trials where the target platform was visible or hidden. RESULTS: Greater quantity was associated with reduced SWM-related activity in the dorsolateral prefrontal cortex (F(1, 167) = 4.15, p = .04). Greater frequency was associated with reduced SWM-related activity in the hippocampus (F(1, 167) = 4.34, p = 0.039). Greater quantity was associated with longer search times (r = 0.21, p = .005) and greater platforms found (r = 0.19, p = .01) in VISIBLE trials. We did not find a relationship between drinking quantity or frequency and gender on SWM-related activity, although men found more platforms in both HIDDEN (F(1, 168) = 11.7, p = 0.0008) and VISIBLE (F(1, 168) = 23.0, p < .0001) trials compared to women. CONCLUSIONS: Altered SWM-related hippocampal function relating to alcohol use in young adults raises questions regarding the impact on young adult health and the nature of the findings. Future studies should examine whether these differences may lead to cognitive deficits later in life.

Synergistic effects of combined vaccination with BCG and influenza vaccines on spatial cognition and hippocampal plasticity in rats.

Previous study has demonstrated the neurobeneficial role of BCG and influenza vaccines. Based on this, our study concentrated on the synergistic effects on development of central nervous system by combined vaccination with BCG and influenza vaccines in rats. Our results displayed that pups combinedly vaccinated with BCG and influenza vaccines showed a significant enhance in spatial cognition, induction of LTP, hippocampal neurogenesis and morphology of dendritic spines compared with pups vaccinated with BCG solely. Furthermore, combined vaccination with BCG and influenza vaccines showed higher expression of BDNF, IGF-1, IL-4, IFN-γ and lower IL-1ß, TNF-α and IL-6 than BCG. Taken together, combined vaccination with BCG and influenza vaccines presented synergistic effects on spatial cognition and hippocampal plasticity in rats.

NMDA Receptor-Dependent Dynamics of Hippocampal Place Cell Ensembles.

The hippocampus is a key brain area to encoding and storing memories. Hippocampal place cells encode the position of an animal in space by firing when the subject is at a specific location in the environment. Therefore, place cells are considered essential to spatial memory and navigation. It has recently been revealed that place-cell activity is not constant even in a familiar environment, but changes dynamically over time. However, the mechanism behind these changes in activity is not yet fully understood. In this study, the activity of hippocampal CA1 neurons of male mice was tracked during repeated performances of a spatial task in a virtual reality environment. By comparing place-cell ensemble representations among repeated performance of the task, the overlap rate of the active place-cell population was found to be time dependent but independent of the number of tasks within a fixed time. These findings suggest that place codes change automatically and at a constant speed. Furthermore, the dynamics of place-cell activity were found to be suppressed by an NMDA receptor antagonist. In summary, the spontaneously dynamic nature of place-cell activity is at least in part regulated by NMDA receptors, and the dynamics may encode temporal information of episodes.SIGNIFICANCE STATEMENT Place-cell activity in the hippocampal CA1 area is not stable even in a familiar environment, but changes dynamically over time. However, the mechanism behind these changes is unknown. Using in vivo calcium imaging, activity of CA1 neurons were tracked during multiple sessions with variable intervals. The overlap rate of the active place-cell population was constant regardless of the number of tasks within a fixed time. Furthermore, the dynamics were suppressed by an NMDA receptor antagonist. This NMDA receptor-dependent, continuous change in the place-cell activity may encode temporal information of episodes.

Effects of pulsed electromagnetic fields on learning and memory abilities of STZ-induced dementia rats.

INTRODUCTION: Recent studies have shown that pulsed electromagnetic field (EMF) has therapeutic potential for dementia, but the associated neurobiological effects are unclear. This study aimed to determine the effects of pulsed EMF on Streptozotocin (STZ)-induced dementia rats. METHODS: Forty Sprague-Dawley rats were randomly allocated to one of the four groups: (i) control, (ii) normal saline injection (sham group), (iii) STZ injection (STZ group) and (iv) STZ injection with pulsed EMF exposure (PEMF, 10 mT at 20 Hz) (STZ + MF group). Morris water maze was used to assess the learning and memory abilities. Insulin growth factors 1 and 2 (IGF-1 and IGF-2) gene expression were determined by quantitative PCR. RESULTS: The results showed that the mean escape latency in STZ-induced dementia rats was reduced by 66% under the exposure of pulsed EMF. Compared with the STZ group, the swimming distance and the time for first crossing the platform decreased by 55 and 41.6% in STZ + MF group, respectively. Furthermore, the IGF-2 gene expression significantly increased compared to that of the STZ group. CONCLUSIONS: Our findings indicate that the pulsed EMF exposure can improve the ability of learning and memory in STZ-induced dementia rats and this effect may be related to the process of IGF signal transduction, suggesting a potential role for the pulsed EMF for the amelioration of cognition impairment.