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

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

OBJECTIVE: Sequelae of behavioral impairments associated with human traumatic brain injury (TBI) include neurobehavioral problems. We compared exploratory, cognitive, and depressive-like behaviors in pediatric and adult male mice exposed to controlled cortical impact (CCI).METHODS: Pediatric (21 to 25 days old) and adult (8 to 12 weeks old) male C57Bl/6 mice underwent CCI at a 2-mm depth of deflection. Hematoxylin and eosin staining was performed 3 to 7 days after recovery from CCI, and injury volume was analyzed using ImageJ. Neurobehavioral characterization after CCI was performed using the Barnes maze test (BMT), passive avoidance test, open-field test, light/dark test, tail suspension test, and rotarod test. Acutely and subacutely (3 and 7 days after CCI, respectively), CCI mice showed graded injury compared to sham mice for all analyzed deflection depths.RESULTS: Time-dependent differences in injury volume were noted between 3 and 7 days following 2-mm TBI in adult mice. In the BMT, 2-mm TBI adults showed spatial memory deficits compared to sham adults (P < 0.05). However, no difference in spatial learning and memory was found between sham and 2-mm CCI groups among pediatric mice. The open-field test, light/dark test, and tail suspension test did not reveal differences in anxiety-like behaviors in both age groups.CONCLUSION: Our findings revealed a graded injury response in both age groups. The BMT was an efficient cognitive test for assessing spatial/non-spatial learning following CCI in adult mice; however, spatial learning impairments in pediatric mice could not be assessed.
Adult ; Animals ; Brain Injuries ; Eosine Yellowish-(YS) ; Hematoxylin ; Hindlimb Suspension ; Humans ; Learning ; Male ; Memory ; Mice ; Rotarod Performance Test ; 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

BACKGROUND AND PURPOSE: This study was performed to newly develop the Way-Finding Ability Scale (WFAS) for middle-aged and older adults and validate its clinical utility. METHODS: The participants for verifying construct validity included 324 adults aged from 45 to 79 years, and 22 normal old adults without way-finding deficit (WFD), 41 amnestic mild cognitive impairment (aMCI), and 35 patients with Parkinson's disease (PD-MCI) for verifying discriminant validity. All participants were administered the newly constructed 28-item WFAS. RESULTS: Exploratory factor analysis of the WFAS revealed a four-factor solution (sense of direction and inattention, spatial learning and memory, strategic ability, and cardinal direction). This four-factor structure was confirmed by confirmatory factor analysis. The discriminant validity was examined by administering the WFAS to normal older adults and two patient groups (aMCI & PD-MCI). The results showed that the total scores of two patient groups were lower than that of normal older adults. The patients with WFD had significantly lower total scores than those without WFD. Interestingly, the total scores of patients without WFD were significantly lower than those of normal older adults suggesting that the cognitive functions associated with way-finding ability (WFA) were partially impaired in aMCI and PD-MCI patients without apparent WFD. The patients with WFD had consistently lower scores in every four-factor than those without WFD. CONCLUSIONS: These results indicated that the WFAS assesses the WFD reliably as well as estimates the degree of decline in WFA.
Adult* ; Cognition ; Humans ; Memory ; Mild Cognitive Impairment ; Parkinson Disease ; Spatial Learning

The purpose of this study was to investigate the effects of post-traumatic stress disorder (PTSD) on electrophysiological characteristics of glutamatergic and GABAergic neurons in dorsal hippocampus (dHPC) and ventral hippocampus (vHPC) in mice, and to elucidate the mechanisms underlying the plasticity of hippocampal neurons and memory regulation after PTSD. Male C57Thy1-YFP/GAD67-GFP mice were randomly divided into PTSD group and control group. Unavoidable foot shock (FS) was applied to establish PTSD model. The spatial learning ability was explored by water maze test, and the changes in electrophysiological characteristics of glutamatergic and GABAergic neurons in dHPC and vHPC were examined using whole-cell recording method. The results showed that FS significantly reduced the movement speed, and enhanced the number and percentage of freezing. PTSD significantly prolonged the escape latency in localization avoidance training, shortened the swimming time in the original quadrant, extended the swimming time in the contralateral quadrant, and increased absolute refractory period, energy barrier and inter-spike interval of glutamatergic neurons in dHPC and GABAergic neurons in vHPC, while decreased absolute refractory period, energy barrier and inter-spike interval of GABAergic neurons in dHPC and glutamatergic neurons in vHPC. These results suggest that PTSD can damage spatial perception of mice, down-regulate the excitability of dHPC and up-regulate the excitability of vHPC, and the underlying mechanism may involve the regulation of spatial memory by the plasticity of neurons in dHPC and vHPC.
Mice ; Male ; Animals ; Stress Disorders, Post-Traumatic ; Hippocampus ; Spatial Learning ; GABAergic Neurons

Children with Specific Learning Disorder (SLD) faces challenges in academic areas and are often negatively labelled. The learning problems in SLD children were mainly due to poor phonological skill but not much was known about the contribution of visuospatial difficulties. Therefore, this study aims to determine the relationship between phonological awareness skills and global visual-spatial abilities among Malay speaking children with SLD, and to compare children with SLD and typical readers on intellectual functioning, phonological awareness and global visual-spatial ability. An equal number of typical readers (n = 36) and children with SLD were recruited. Data were coded and analysed using Kendall’s Tau-b, independent samples t-test and Mann-Whitney U test. Results showed phonological skills have strong negative correlation with global visual-spatial ability (r = .55). The typical readers have significantly higher IQ and better phonological skills and better global visual-spatial skills as compared to the group with SLD. However, there is no conclusive evidence due to specificity of more than one area measured by the assessment tools. Nevertheless, it provides a direction for future research to look into global visual-spatial aspects of SLD to aid in educational instruction in the future, in addition to the long-standing phonology deficit theory.
Specific Learning Disorders ; dyslexia ; phonological awareness, global visual-spatial ability, intellectual functioning

Animals ; Dentate Gyrus ; Hippocampus ; Rats ; Receptors, Adrenergic, beta ; Sleep ; Spatial Learning