The formation, consolidation and retrieval of spatial memory depend on sequential firing patterns of place cells assembling in the hippocampus. Theta sequences of place cells during behavior play a role in acquisition of spatial memory, trajectory prediction and decision making. In awake rest and slow wave sleep, place cell sequences occur during the sharp wave-ripples (SWRs), called "replay", which is crucial for memory consolidation and retrieval. In this review, we summarize the functional significances of theta sequences and SWRs replay sequences and the mechanism of these sequences. We also discuss the relationship between theta and replay sequences with the formation of spatial memory. We propose the research direction in this field in future and aim to provide new ideas for related researches.
Hippocampus ; Sleep ; Spatial Memory ; Wakefulness

The objective of this study was to elucidate the effect of chronic stress (CS) on dopamine (DA) level and synaptic efficiency in the hippocampal dentate gyrus (DG) during spatial learning and memory. Sprague Dawley (SD) male rats were randomly divided into control group and CS group (n = 10). CS group was treated with chronic mild unpredictable stress, and control group did not receive any treatments. The levels of epinephrine and corticosterone (CORT) in serum were measured by using enzyme-linked immunosorbent assay (ELISA); the spatial learning and memory abilities of rats were measured by Morris water maze (MWM) test. Meanwhile, the amplitude of field excitatory postsynaptic potential (fEPSP) and concentration of DA in the DG region were determined by in vivo electrophysiology, microdialysis and HPLC techniques during MWM test in rats. After that, the DA D1 receptor (D1R) and its key downstream members in DG were examined by immunohistochemistry or Western blot assay. The results showed that the levels of epinephrine and CORT in the serum of the rats in CS group were significantly increased compared with those in the control group (P < 0.05). In CS group rats, the escape latency was significantly prolonged and the number of platform crossing was markedly decreased during MWM test, compared with those in control group (P < 0.05). Furthermore, the amplitude of fEPSP in the DG was not changed during MWM test in CS rats, while it was significantly increased on the 3rd day of MWM test in control group (P < 0.05). Compared with baseline or control group, CS group showed significantly increased DA level from the 1st to 3rd days of MWM test in the DG (P < 0.05). In addition, the protein expression of D1R was markedly up-regulated in the DG in CS group, while the protein expression levels of p-PKA, p-CREB and BDNF were significantly reduced, compared with those in control group. These results suggest that CS may impair spatial learning and memory abilities in rats through the enhancement of the DA levels in the hippocampal DG.
Animals ; Dentate Gyrus ; Dopamine ; Hippocampus ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Spatial Learning ; Spatial Memory

OBJECTIVES: We aimed to study the role of vestibular input on spatial memory performance in mice that had undergone bilateral surgical labyrinthectomy, semicircular canal (SCC) occlusion and 4G hypergravity exposure. METHODS: Twelve to 16 weeks old ICR mice (n=30) were used for the experiment. The experimental group divided into 3 groups. One group had undergone bilateral chemical labyrinthectomy, and the other group had performed SCC occlusion surgery, and the last group was exposed to 4G hypergravity for 2 weeks. The movement of mice was recorded using camera in Y maze which had 3 radial arms (35 cm long, 7 cm high, 10 cm wide). We counted the number of visiting arms and analyzed the information of arm selection using program we developed before and after procedure. RESULTS: The bilateral labyrinthectomy group which semicircular canal and otolithic function was impaired showed low behavioral performance and spacial memory. The semicircular canal occlusion with CO₂ laser group which only semicircular canal function was impaired showed no difference in performance activity and spatial memory. However the hypergravity exposure group in which only otolithic function impaired showed spatial memory function was affected but the behavioral performance was spared. The impairment of spatial memory recovered after a few days after exposure in hypergravity group. CONCLUSIONS: This spatial memory function was affected by bilateral vestibular loss. Space-related information processing seems to be determined by otolithic organ information rather than semicircular canals. Due to otolithic function impairment, spatial learning was impaired after exposure to gravity changes in animals and this impaired performance was compensated after normal gravity exposure.
Animals ; Arm ; Automatic Data Processing ; Gravitation ; Hypergravity ; Memory ; Mice ; Mice, Inbred ICR ; Otolithic Membrane ; Semicircular Canals ; Spatial Learning ; Spatial Memory

Numerous studies have implicated the hippocampus in the encoding and storage of declarative and spatial memories. Several models have considered the hippocampus and its distinct subfields to contain homogeneous pyramidal cell populations. Yet, recent studies have led to a consensus that the dorso-ventral and proximo-distal axes have different connectivities and physiologies. The remaining deep-superficial axis of the pyramidal layer, however, remains relatively unexplored due to a lack of techniques that can record from neurons simultaneously at different depths. Recent advances in transgenic mice, two-photon imaging and dense multisite recording have revealed extensive disparities between the pyramidal cells located in the deep and the superficial layers. Here, we summarize differences between the two populations in terms of gene expression and connectivity with other intra-hippocampal subregions and local interneurons that underlie distinct learning processes and spatial representations. A unified picture will emerge to describe how such local segregations can increase the capacity of the hippocampus to compute and process numerous tasks in parallel.
Animals ; Consensus ; Gene Expression ; Hippocampus ; Interneurons ; Learning ; Memory ; Mice ; Mice, Transgenic ; Neurons ; Pyramidal Cells ; Spatial Memory

Long-term exposure to high altitude affects spatial working memory. Previous studies have focused on the analysis of electroencephalogram (EEG) components in time domain rather than in frequency domain. To explore the influence of long-term high altitude exposure on time dynamic characteristics and neural oscillation process of the spatial working memory, n-back task combined with the technology of event related potential recording was performed on 20 young migrants who grew at low altitude before the age of 18 and moved to high altitude more than three years ago, and 21 young people who had never been to the high altitude. EEG data were recorded, and the time domain and frequency domain analyses were performed. The results showed that the response time was longer and the accuracy rate was lower under the 2-back condition in the high altitude group compared with those in low altitude group. The late positive potential (LPP) amplitude was more negative, P2 amplitude was more positive in the 2-back condition, and the power value of early delta frequency band (1-4 Hz, 160-300 ms) was larger, while the power values of late delta frequency band (1-4 Hz, 450-650 ms) and theta frequency band (4-8 Hz, 450-650 ms) were smaller in the high altitude group compared with those in low altitude group. The results suggested that long-term exposure to high altitude affected the spatial working memory ability of the migrants, which was reflected in the lack of attention resources in the later matching stage, decreased response inhibition ability and information maintenance ability, and thus resulted in impaired spatial working memory.
Altitude ; Brain ; physiopathology ; Electroencephalography ; Humans ; Memory, Short-Term ; Reaction Time ; Spatial Memory ; Transients and Migrants

OBJECTIVETo explore the abilities of verbal and visual-spatial memory in Chinese children with developmental dyslexia.

METHODSThirty-two children with developmental dyslexia (aged 8-12 years) and thirty-nine age- and gender-matched normal children were involved in the study. Their verbal short-term and verbal working memories were measured using the digit ordering and the digit span tests, respectively. Their visual-spatial short-term and visual-spatial working memories were examined using the forward and backward block-tapping tests, respectively.

RESULTSThe DD children scored lower in the digit ordering and the digit span tests than the control children (P<0.05). The scores for the forward and backward block-tapping tests did not vary between the two groups (P>0.05).

CONCLUSIONSThe children with DD have the deficits in both verbal short-term memory and verbal working memory.

OBJECTIVE: A radial arm maze (RAM) is an essential tool for assessing spatial learning and memory. Although this tool is widely used to study deficits in spatial memory in animal models, it has several restrictions that prevent its adaptation to human research and training. Therefore, we developed a head-mounted-display RAM (HMD-RAM) program for humans and verified its validity by comparing it to the results obtained by previous RAM studies. We also compared the HMD and a flat monitor as experimental devices. METHODS: Forty participants were recruited for the current study (Study 1: 20 participants with the HMD device; Study 2: 20 participants with the flat monitor). They navigated a virtual room as a first-person viewer and used environmental landmarks to remember their spatial position and orientation. The main dependent measures were working memory error, reference memory error, detection time, travel distance, and participant’s head movements. To validate the program, participants also conducted neuropsychological assessments and self-reported measures. RESULTS: The results for HMD-RAM tasks were consistent with the results of previous research conducted on animals, and the HMD elicited a higher sense of presence, immersion, and simulator sickness than the flat monitor. According to post-experiment questions on navigation strategy, creating landmarks was important when people were discovering locations in their environment, and an HMD was beneficial for better navigation strategy. CONCLUSION: These results suggest that the HMD-RAM is valuable for estimating spatial learning and memory in humans and may be a useful tool for early diagnosis of deficits in spatial learning and memory, including amnestic mild cognitive impairment and Alzheimer’s disease.
Animals ; Arm* ; Early Diagnosis ; Head Movements ; Humans ; Immersion ; Memory* ; Memory, Short-Term ; Mild Cognitive Impairment ; Models, Animal ; Spatial Learning* ; Spatial Memory

Rapid eye movement (REM) sleep has an essential role in the process of learning and memory in the hippocampus. It has been reported that linalool, a major component of Lavandula angustifolia, has antioxidant, anti-inflammatory, and neuroprotective effects, along with other effects. However, the effect of linalool on the cognitive impairment and behavioral alterations that are induced by REM-sleep deprivation has not yet been elucidated. Several studies have reported that REM-sleep deprivation-induced memory deficits provide a well-known model of behavioral alterations. In the present study, we examined whether linalool elicited an anti-stress effect, reversing the behavioral alterations observed following REM-sleep deprivation in mice. Furthermore, we investigated the underlying mechanism of the effect of linalool. Spatial memory and learning memory were assessed through Y maze and passive avoidance tests, respectively, and the forced swimming test was used to evaluate anti-stress activity. The mechanisms through which linalool improves memory loss and behavioral alterations in sleep-deprived mice appeared to be through an increase in the serotonin levels. Linalool significantly ameliorated the spatial and learning memory deficits, and stress activity observed in sleep-deprived animals. Moreover, linalool led to serotonin release, and cortisol level reduction. Our findings suggest that linalool has beneficial effects on the memory loss and behavioral alterations induced by REM-sleep deprivation through the regulation of serotonin levels.
Animals ; Cognition Disorders ; Hippocampus ; Hydrocortisone ; Lavandula ; Learning ; Memory Disorders* ; Memory* ; Mice ; Neuroprotective Agents ; Physical Exertion ; Serotonin ; Sleep, REM ; Spatial Memory

OBJECTIVE: Although, accumulating evidence is delineating a neuroprotective and neurotrophic role for lithium (Li), inconsistent findings have also been reported in human studies especially. Moreover, the effects of Li infusion into the hippocampus are still unknown. The aims of this work were (a) to assess whether basal synaptic activity and long-term potentiation (LTP) in the hippocampus are different in regard to intrahippocampal Li infusion; (b) to assess spatial learning and memory in rats chronically treated with LiCO₃ in the Morris water maze. METHODS: Field potentials were recorded form the dentate gyrus, stimulating perforant pathways, in rats chronically (20 mg/kg for 40 days) or acutely treated with LiCO₃ and their corresponding control rats. In addition, performance of rats in a Morris water maze was measured to link behaviour of rats to electrophysiological findings. RESULTS: LiCO₃ infusion into the hippocampus resulted in enhanced LTP, especially in the late phases, but attenuated LTP was observed in rats chronically treated with Li as compared to controls. Li-treated rats equally performed a spatial learning task, but did spend less time in target quadrant than saline-treated rats in Morris water maze. CONCLUSION: Despite most data suggest that Li always yields neuroprotective effects against neuropathological conditions; we concluded that a 40-day treatment of Li disrupts hippocampal synaptic plasticity underlying memory processes, and that these effects of prolonged treatment are not associated with its direct chemical effect, but are likely to be associated with the molecular actions of Li at genetic levels, because its short-term effect preserves synaptic plasticity.
Adult ; Animals ; Dentate Gyrus ; Hippocampus ; Humans ; Learning ; Lithium ; Long-Term Potentiation ; Memory ; Neuronal Plasticity ; Neuroprotective Agents ; Perforant Pathway ; Rats ; Spatial Learning ; Spatial Memory ; Water

OBJECTIVE: Hypoxic-ischemic (HI) brain injury in the human perinatal period often leads to significant long-term neurobehavioral dysfunction in the cognitive and sensory-motor domains. Using a neonatal HI injury model (unilateral carotid ligation followed by hypoxia) in postnatal day seven rats, the present study investigated the long-term effects of HI and potential behavioral protective effect of pentoxifylline. METHODS: Seven-day-old rats underwent right carotid ligation, followed by hypoxia (FiO2 = 0.08). Rats received pentoxifylline immediately after and again 2 hours after hypoxia (two doses, 60–100 mg/kg/dose), or serum physiologic. Another set of seven-day-old rats was included to sham group exposed to surgical stress but not ligated. These rats were tested for spatial learning and memory on the simple place task in the Morris water maze from postnatal days 77 to 85. RESULTS: HI rats displayed significant tissue loss in the right hippocampus, as well as severe spatial memory deficits. Low-dose treatment with pentoxifylline resulted in significant protection against both HI-induced hippocampus tissue losses and spatial memory impairments. Beneficial effects are, however, negated if pentoxifylline is administered at high dose. CONCLUSION: These findings indicate that unilateral HI brain injury in a neonatal rodent model is associated with cognitive deficits, and that low dose pentoxifylline treatment is protective against spatial memory impairment.
Animals ; Anoxia ; Brain Injuries ; Brain ; Cognition Disorders ; Hippocampus ; Humans ; Hypoxia-Ischemia, Brain ; Learning ; Ligation ; Memory ; Pentoxifylline ; Rats ; Rodentia ; Spatial Learning ; Spatial Memory ; Water