Changes In Spatial Memory Research Articles

GABA Signaling in Spatial Memory changes in Animal Model of Alzheimer’s disease

GABA Signaling in Spatial Memory changes in Animal Model of Alzheimer’s disease

Effect of curcumin-donepezil combination on spatial memory, astrocyte activation, and cholinesterase expressions in brain of scopolamine-treated rats.

The study investigated the effect of co-administration of curcumin and donepezil on several markers of cognitive function (such as spatial memory, astrocyte activation, cholinesterase expressions) in the brain cortex and hippocampus of scopolamine-treated rats. For seven consecutive days, a pre-treatment of curcumin (50mg/kg) and/or donepezil (2.5mg/kg) was administered. On the seventh day, scopolamine (1mg/kg) was administered to elicit cognitive impairment, 30min before memory test was conducted. This was followed by evaluating changes in spatial memory, cholinesterase, and adenosine deaminase (ADA) activities, as well as nitric oxide (NO) level were determined. Additionally, RT-qPCR for glial fibrillary acidic protein (GFAP) and cholinesterase gene expressions was performed in the brain cortex and hippocampus. Also, GFAP immunohistochemistry of the brain tissues for neuronal injury were performed in the brain cortex and hippocampus. In comparison to the control group, rats given scopolamine had impaired memory, higher levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ADA activities, as well as elevated markers of oxidative stress. In addition to enhanced GFAP immunoreactivity, there was also overexpression of the GFAP and BChE genes in the brain tissues. The combination of curcumin and donepezil was, however, observed tobetter ameliorate these impairments in comparison to thedonepezil-administered rat group. Hence, this evidence provides more mechanisms to support the hypothesis that the concurrent administration of curcumin and donepezil mitigates markers of cognitive dysfunction in scopolamine-treated rat model.

Abstract TMP115: White Matter Loss and Neurological Deficits Due to Chronic Global Hypoperfusion Are Worsened in a Mouse Model of Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is a disease of small and medium-sized vessels, characterized by amyloid deposition in the brain vasculature. The incidence of CAA increases with age and pathophysiological features (i.e., amyloid) overlap with that of Alzheimer’s Disease (AD). Cerebral hypoperfusion (CH) impairs the integrity of the blood brain barrier and contributes to cerebral atrophy and white matter loss. However, the link between hypoperfusion and vascular amyloid deposition remains understudied. We induced global CH with bilateral carotid artery stenosis (BCAS) in CAA mice of both sexes. We hypothesized that chronic CH accelerates cognitive decline in CAA, increases white matter damage, and induces gliotic changes in the brain. Using a mouse model of CAA (Tg-SwDI), male and female mice (12wks-old) were randomized to either BCAS (n=15) or sham (n=11) surgery. Cognitive (Y-maze (YM), NORT, Water Maze (WM)) and motor function (Open Field (OF)) testing was performed by a blinded investigator prior to surgery (baseline) and at regular intervals until tissue harvest 6 months post-BCAS. Brains were harvested for immunohistochemical (IHC) analysis (Kluver-Barrera (KB), Iba-1, GFAP, Myelin Basic Protein (MBP)) and flow cytometry. Sex-specific changes in spatial memory (YM) and learning (NORT/WM) were present in CAA BCAS mice, with females having an earlier onset of deficits than males. Female BCAS mice displayed deficits in cognition (NORT) at 3 (p=.003), 4 (YM, p=.0007), and 5-months (p=.01) after BCAS. Male BCAS mice demonstrated cognitive deficits 5 months post-BCAS (NORT, p=.001). Both female and male BCAS mice had poorer cognition (WM, p=.001) 6 months post-BCAS. IHC demonstrated increased demyelination (MBP, p=.004) and atrophy (KB) in the anterior corpus collosum (p=.04) and significant cortical gliosis (p=.02). The hippocampus contained higher numbers of NOX2-expressing (p= .051) and lipid-rich microglia in BCAS (p=.042) versus sham mice. Neuronal loss and increases in endothelial-cell amyloid levels were also found in BCAS CAA mice, using flow cytometry. Global CH accelerates cognitive deficits in a CAA model, an effect that is accelerated in female mice and led to gliosis, white matter damage, and lipid-accumulating microglia.

Acupuncture Improves Synaptic Plasticity of SAMP8 Mice through the RhoA/ROCK Pathway.

Studies have found synaptic plasticity damage to be an early marker of Alzheimer's disease (AD). RhoA/ROCK pathway is involved in the regulation of synaptic plasticity. Acupuncture can significantly improve the cognitive state of AD. We aimed to use modern biological technology to detect the changes in synaptic plasticity and RhoA/ROCK pathway in SAMP8 mice, as well as the intervention effect of acupuncture. Morris water maze and electrophysiological techniques were used in vivo to detect the changes in spatial memory and LTP of mice. Golgi Cox staining and CASEVIEWER2.1 software were used to quantitatively analyze the changes in the morphology and number of dendritic spines in the hippocampus of mice. The activity of RhoA and ROCK2 in the hippocampus of mice was detected, respectively, by pull-down technique and ELISA. WB technique was used to detect the protein expression of ROCK2 and phosphorylation level of MLC2, LIMK2, and CRMP2 in the hippocampus of mice. The neurobehavior and synaptic plasticity of 8-month-old SAMP8 mice were found to be significantly impaired. Acupuncture could improve the spatial learning and memory ability of SAMP8 mice, and partially prevent the reduction in the number of spines on the secondary branches of the apical dendrites in the hippocampus and the attenuation of LTP. The RhoA/ROCK pathway was significantly activated in the hippocampus of 8-month-old SAMP8 mice, and acupuncture had an inhibitory effect on it. Acupuncture can improve synaptic plasticity by inhibiting the abnormal activation of the RhoA/ROCK pathway, and improve the spatial learning and memory ability of AD, so as to achieve the purpose of treating AD.

Abstract 105: Sex Differences In The Response To Global Cerebral Hypo-Perfusion In A Mouse Model Of Cerebral Amyloid Angiopathy

Cerebral amyloid angiopathy (CAA) is a disease of small and medium-sized vessels, characterized by amyloid deposition. The incidence of CAA increases with age and evidence reveals worsened cognition in females compared to males. Cerebral hypoperfusion, or a decrease in cerebral blood flow (CBF), changes the integrity of the blood brain barrier and contributes to microhemorrhages, cerebral atrophy, and white matter loss. However, the link between vascular amyloid deposition and hypoperfusion remains understudied. We induced global cerebral hypoperfusion with bilateral carotid artery stenosis (BCAS) in CAA mice of both sexes and examined cognitive deficits, white matter loss, and cerebral gliosis. We hypothesize that chronic cerebral hypoperfusion will accelerate cognitive decline in CAA, increase white matter damage, and induce gliotic changes in the brain.Using a mouse model of CAA (Tg-SwDI), male and female mice (3 months of age) were randomized to either BCAS (n=15) or sham (n=11) surgery using 0.18mm coils to induce global cerebral hypoperfusion. Cognitive (Y-maze (YM), NORT, Water Maze (WM)) and motor function (Open Field (OF)) testing was performed by a blinded investigator prior to surgery (baseline) and at regular intervals until tissue harvest 6 months post-BCAS (PB). The brain and brainstem were harvested for immunohistochemical (IHC) analysis (Kluver-Barrera (KB), Iba-1, GFAP, Myelin Basic Protein (MBP)).Sex-specific changes in spatial memory (YM) and learning (NORT/WM) were present in BCAS mice. Female BCAS mice displayed greater deficits in cognition (NORT) at 3 (p=.0028), 4 (YM, p=.0007), and 5-months PB (NORT, p=.0149). Male BCAS mice demonstrated similar cognitive deficits, but at a later timepoint of 5 months PB (NORT, p=.0007). Both female and male BCAS mice had poorer cognition (WM) and motor function (OF, p=.0011/.0055) 6 months PB. IHC demonstrated increased demyelination (MBP) (p=.0038) and atrophy (KB) in the anterior corpus collosum (p=.0447) and significant gliosis (p=.0230).This study shows that chronic global hypoperfusion accelerates cognitive deficits in a CAA model, an effect that is accelerated in female mice. BCAS led to gliotic changes and demyelination associated with white matter damage in the brain.

Effect of resistance and endurance training with ursolic acid on oxidative stress and cognitive impairment in hippocampal tissue in HFD/STZ-induced aged diabetic rats.

The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf2/Keap1/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf2/Keap1/ARE pathway in the brain of older diabetic rats. 23-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=8). UA supplementation (250 mg/kg, daily) was administered along with resistance (60% maximum capacity of voluntary carrying [MVCC], 14-20 climbs) or endurance training (60-75% velocity at maximal oxygen uptake [vVO2max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf2, Keap1, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue. The results showed positive effect of resistance training (P≤0.001) on Nrf2. There was endurance training with supplementation main effect (P=0.018) on Keap1 concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤0.05); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups. It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf2 and some antioxidant markers. However, more research is needed to elucidate UA's interaction effects and exercise interventions in diabetic situations.

State of spatial memory and antioxidant system activity of rats in the dynamics of development of blast-induced traumatic brain injury

The main purpose of this study was to investigate the changes in spatial memory and catalase activity in dynamics in the blast-induced traumatic brain injury (bTBI). The experiment was carried out on 67 albino male Wistar rats, which were randomly divided into three groups: I group – experimental (n=34), animals were subjected to inhalation anesthesia with halothane, fixed and was simulated blast-induced traumatic brain injury was simulated by generating a shock wave with an overpressure of 26.4±3.6 kPa, II group – sham (n=34), animals which were subjected only to inhalation anesthesia and fixation and III group – intact (n=34). After the study of behavior, euthanasia was performed, blood and brain were taken shelter. Histopathological examination of the brain showed disturbances both of hippocampal neurons and microcirculature. In the dynamics of the post-traumatic period of mild bTBI there was observed a significant (p<0.01) impairment of rats spatial memory in the experimental group, which was established as a prolongation of latent time of the search in the Barnes maze: by 39% – on day 1, by 76% – on day 3, by 65% – on day 7 and by 61% – on day 14 of the study. The analysis of catalase activity revealed a significant decrease of this enzyme activity in blood plasma of the rats in the experimental group in comparison with rats of sham and intact groups: on day 1 – by 35% (p<0.01), on day 3 – by 27% (p<0.01) and by 12% on day 7 of the post-traumatic period (p<0.05), which indicates the involvement of catalase in the reaction of hydrogen peroxide inactivation. Correlation analysis between spatial memory and catalase activity in experimental rats showed a negative relationship of medium degree on day 1 (r=-0.3, p<0.01) and a negative relationship (r=-0.2, p<0.01) of weak degree on day 3 of post-traumatic period, indicating increased formation of free radicals during this period. One-way analysis of variance showed a significant (H1, p<0.01) effect of changes in the catalase activity of rat blood plasma on the state of spatial memory in the Barnes maze during 14 days of the post-traumatic period. It was established that oxidative stress is an important link in pathogenesis of the spatial memory disorders in animals with mild bTBI in the first week of the post-traumatic period.

Aged rats learn Morris Water maze using non-spatial search strategies evidenced by a parameter-based algorithm.

Spatial learning and memory are used by all individuals who need to move in a space. Morris water maze (MWM) is an accepted method for its evaluation in murine models and has many protocols, ranging from the classic parameters of latency, distance, and number of crossings to the platform zone, to other more complex methods involving computerized trajectory analysis. Algorithm-based SS analysis is an alternative that enriches traditional classic parameters. We developed a non-computerized parameter-based Search Strategy Algorithm (SSA), to classify strategies and detect changes in spatial memory and learning. For this, our algorithm was validated using young and aged rats, evaluated by two observers who classified the trajectories of the rats based on the effectiveness, localization, and precision to reach the platform. SSA is classified into 10 categories, classified by effectiveness, initial direction, and precision. Traditional measurements were unable to show significant differences in the learning process. However, significant differences were identified in SSA. Young rats used a direct search strategy (SS), while aged rats preferred indirect ones. The number of platform crossings was the only variable to show the difference in the intermediate probe trial. The parameter-based algorithm represents an alternative to the computerized SS methods to analyze the spatial memory and learning process in young and age rats. We validate the use of SSA as an alternative to computerized SS analysis spatial learning acquisition. We demonstrated that aged rats had the ability to learn spatial memory tasks using different search strategies. The use of SSA resulted in a reliable and reproducible method to analyze MWM protocols.

An investigative study to demonstrate the link between combined intake of marijuana and codeine in Alzheimer’s disease pathology

AbstractBackgroundAssessment of the contributory role of combined ingestion of codeine and Marijuana to the pathogenesis of Alzheimer’s disease which is the most common cause of dementia among older adults; by studying changes in spatial memory, astrocytic proliferation, Nissl bodies, lipid peroxidation and antioxidant enzyme status.MethodTwenty (20) adult male Wistar rats used for this study were divided into four groups (n=5): the control, codeine, marijuana and a group given both codeine and marijuana. The animals were exposed to the drug treatment for ten (10) days. Behavioral tests for memory using Y maze was conducted. The animals were euthanized and brain tissues fixed in 4% PFA and processed for Cresyl fast Violet stain for Nissl bodies, glial fibrillary acidic protein (GFAP) immunohistochemistry for astrocytes with focus on prefronto‐hippocampus cortex. Serum antioxidant activity of superoxide dismutase (SOD), glucose‐6‐phosphodehydrogenase (G6PDH), Lactate dehydrogenase (LDH) activity and lipid peroxidation enzyme marker –Malondialdehyde (MDA) were accessed.ResultThe prefronto‐hippocampal cortex of rats exposed to Codeine, Marijuana (B and C) and those give both drugs (D) were characterized with loss of neurons, necrosis, chromatolysis and proliferation of astrocytes as compared with the control. However, combined drug use has more severity in the loss of loss of spatial memory, reduced number of arm entries and increased immobility time as compared with the control, codeine and Marijuana only groups. Group D, had severe decline in SOD and G6PDH serum activity and an elevation in lipid peroxidation as compared with B and C.Conclusionthe combine use of codeine and marijuana has more deleterious effects on neuron cell integrity, memory, cognition and antioxidant enzymes because it induces severe oxidative stress that predisposes to the development of Alzheimer’s disease in an individual.

Bright light exposure induces dynamic changes of spatial memory in nocturnal rodents

Bright light has been reported to improve spatial memory of diurnal rodents, yet how it will influence the spatial memory of nocturnal rodents is unknown. Here, we found that dynamic changes in spatial memory and anxiety were induced at different time point after bright light treatment. Mice maintained in brighter light exhibited impaired memory in Y maze at one day after bright light exposure, but showed significantly improved spatial memory in the Y maze and Morris water maze at four weeks after bright light exposure. We also found increased anxiety one day after bright light exposure, which could be the reason of impaired memory. However, no change of anxiety was detected after four weeks. Thus, we further explore the underlying mechanism of the beneficial effects of long term bright light on spatial memory. Golgi staining indicated that the structure of dendritic spines changed, accompanied by increased expression of synaptophysin and postsynaptic density 95 in the hippocampus. Further research has found that bright light treatment leads to elevated CaMKII/CREB phosphorylation levels in the hippocampus, which are associated with synaptic function. Moreover, higher expression of brain-derived neurotrophic factor (BDNF) was followed by increased phosphorylated TrkB levels in the hippocampus, indicating that BDNF/TrkB signaling is also activated during this process. Taken together, these findings revealed that bright light exposure with different duration exert different effects on spatial memory in nocturnal rodents, and the potential molecular mechanism by which long term bright light regulates spatial memory was also demonstrated.

Testing the precision of spatial memory representations using a change-detection task: effects of viewpoint change

ABSTRACT The brain encodes spatial information in at least two distinct ways: egocentric representations encode locations relative to the observer, whereas allocentric representations encode locations relative to the environment. Both inform spatial memory, but the extent to which they influence behaviour varies depending on the task. In two preregistered experiments we used a psychophysical approach to measure the precision of spatial memory while varying ego- and allocentric task demands. Participants attempted to detect the changed location of one of four objects when seen from a new viewpoint. In both experiments (one using a Same/Different task, the other a 2AFC task), psychophysically-determined change detection thresholds showed a monotonic but non-linear increase as the degree of viewpoint change increased. Our findings were consistent with a preregistered model which shows how, governed by distinct ego- and allocentric contributions, the precision of spatial memory changes lawfully as a function of viewpoint shift.

Delayed effects of a single-dose whole-brain radiation therapy on glucose metabolism and myelin density: a longitudinal PET study

Purpose Radiotherapy is an important treatment option for brain tumors, but the unavoidable irradiation of normal brain tissue can lead to delayed cognitive impairment. The mechanisms involved are still not well explained and, therefore, new tools to investigate the processes leading to the delayed symptoms of brain irradiation are warranted. In this study, positron emission tomography (PET) is used to explore delayed functional changes induced by brain irradiation. Materials and methods Male Wistar rats were subjected to a single 25-Gy dose of whole brain X-ray irradiation, or sham-irradiation. To investigate delayed effects of radiation on cerebral glucose metabolism and myelin density, 18F-fluorodeoxyglucose (18F-FDG) PET scans were performed at baseline and on day 64 and 94, whereas N-11C-methyl-4,4′-diaminostilbene (11C-MeDAS) PET scans were performed at baseline and on day 60 and 90 post-irradiation. In addition, the open field test (OFT) and novel spatial recognition (NSR) test were performed at baseline and on days 59 and 89 to investigate whether whole brain irradiation induces behavioral changes. Results Whole-brain irradiation caused loss of bodyweight and delayed cerebral hypometabolism, with 18F-FDG uptake in all brain regions being significantly decreased in irradiated rat on day 64 while it remained unchanged in control animals. Only amygdala and cortical brain regions of irradiated rats still showed reduced 18F-FDG uptake on day 94. 11C-MeDAS uptake in control animals was significantly lower on days 60 and 90 than at the baseline, suggesting a reduction in myelin density in young adults. In irradiated animals, 11C-MeDAS uptake was similarly reduced on day 60, but on day 90 tracer uptake was somewhat increased and not significantly different from baseline anymore. Behavioral tests showed a similar pattern in control and irradiated animals. In both groups, the OFT showed significantly reduced mobility on days 59 and 89, whereas the NSR did not reveal any significant changes in spatial memory over time. Interestingly, a positive correlation between the NSR and 11C-MeDAS uptake was observed in irradiated rats. Conclusions Whole-brain irradiation causes delayed brain hypometabolism, which is not accompanied by white matter loss. Irradiated animals showed similar behavioral changes over time as control animals and, therefore, cerebral hypometabolism could not be linked to behavioral abnormalities. However, spatial memory seems to be associated with myelin density in irradiated rats.

Age-related differences in the elderly in a spatial recognition task

ABSTRACTSpatial memory is a cognitive ability which declines with ageing thus showing changes in some process such as the use of allocentric strategies. These age-related changes in spatial orientation suggest that this skill could be an adequate marker of cognitive decline. Many tasks used in investigation to assess spatial memory demand a participant’s active role, which involves that the navigational experience is different for everyone. In this study, the Almeria Spatial Memory Recognition Test (ASMRT), a test based on a recognition paradigm, was used to offer the same experience with the environment. The aim of this research was to determine if the ASMRT is suitable to be applied in the elderly and detect spatial memory differences as one age. The ASMRT and other neuropsychological tests were applied in a sample aged between 50and 79 years. Results revealed a decrease in the ASMRT performance by the older group. No gender differences were found. Performance in attention and visuospatial working memory tests revealed some correlations with the ASMRT performance. In conclusion, this study demonstrates that 70–79-year-old participants clearly show age-related changes in spatial memory. Thanks to its simplicity the ASMRT could be used as a screening test in medical practice.

Fish behavior: A promising model for aquatic toxicology research

Fish behaviors have great potential as models for the study of pharmacology, genetics, and neuroscience. Zebrafish (Danio rerio), Japanese medaka (Oryzias latipes) and Chinese rare minnow (Gobiocypris rarus) are popular freshwater animal models. However, their behavioral use in aquatic toxicology research is generally hampered by oversimplified behavioral tasks and the fact that they are not well-developed animal models for toxicology. Here, this study presented a comparative analysis of multiple behavioral traits (i.e., anxiety-like behavior, novel object recognition, social preferences, habituation to light-dark stimulus and noise stimulus, and spatial learning and memory). We found that only medaka (d-rR) presented a weak or no response to repeated light-dark stimulus and noise stimulus. In addition, no significant behavioral changes were observed for the three species of juvenile fish models after 7 days of exposure to 0.01% v/v carrier solvents (i.e., ethanol, acetone, and DMSO). In contrast to zebrafish and Chinese rare minnow, medaka showed no significant changes in spatial memory after subacute exposure to 1 mg/L imidacloprid or 2.5 μg/L chlorpyrifos (cpf); instead, a hyperactivity response in the open field test and reduced social time were induced by cpf and imidacloprid, respectively. Our results suggest that: (1) behavioral effects are negligible when using <0.01% v/v carrier solvents for behavioral assessment; (2) given the differences in sensitivities of behavioral responses, a single behavior used alone as an endpoint may be insufficient for estimating the toxic impacts of pesticides or other environmental contaminants. In conclusion, these results could have major implications for aquatic toxicology research and water quality monitoring and ecotoxicological risk assessment.

Spatial memory ability during middle age may depend on level of spatial similarity.

Spatial memory impairment is well documented in old age; however, less is known about spatial memory during middle age. We examined the performance of healthy young, middle-aged, and older adults on a spatial memory task with varying levels of spatial similarity (distance). On low similarity trials, young adults significantly outperformed middle-aged adults, who significantly outperformed older adults (Ps < 0.05). On high similarity trials, young adults significantly outperformed middle-aged and older adults (Ps < 0.05); however, middle-aged and older adults did not differ. Subtle age-related changes in spatial memory may emerge during middle age, particularly when spatial similarity is high.

Lingonberries and their two separated fractions differently alter the gut microbiota, improve metabolic functions, reduce gut inflammatory properties, and improve brain function in ApoE−/− mice fed high-fat diet

Lingonberries (LB) have been shown to have beneficial metabolic effects, which is associated with an altered gut microbiota. This study investigated whether the LB-induced improvements were associated with altered gut- and neuroinflammatory markers, as well as cognitive performance in ApoE−/− mice fed high-fat (HF) diets. Whole LB, as well as two separated fractions of LB were investigated. Eight-week-old male ApoE−/− mice were fed HF diets (38% kcal) containing whole LB (wLB), or the insoluble (insLB) and soluble fractions (solLB) of LB for 8 weeks. Inclusion of wLB and insLB fraction reduced weight gain, reduced fat deposition and improved glucose response. Both wLB and insLB fraction also changed the caecal microbiota composition and reduced intestinal S100B protein levels. The solLB fraction mainly induced weight loss in the mice. There were no significant changes in spatial memory, but significant increases in synaptic density in the hippocampus were observed in the brain of mice-fed wLB and insLB. Thus, this study shows that all lingonberry fractions counteracted negative effects of HF feedings on metabolic parameters. Also, wLB and insLB fraction showed to potentially improve brain function in the mice.

2334 Neural correlates of externally Versus internally guided dance-based therapies for people with Parkinson’s disease

OBJECTIVES/SPECIFIC AIMS: Parkinson’s disease (PD) is a condition that affects over a million Americans, and despite current medical therapies, the progression of the disease results in impaired generation of internally timed or guided (IG) movements. To address this loss of motor function, previous rehabilitation therapies have focused on remediating the affected striatal-thalamic-cortical circuits (STC), primarily thought to be responsible in generating timed motor patterns. However, given the disease leads to the cell death of dopaminergic cells that are essential for proper STC function, we propose a motor therapy aimed at utilizing a compensatory parallel cerebellar-thalamic-cortical (CTC) pathway, recruited to perform externally guided (EG) movements, in which gait initiation is driven from sensory input. Our previous study has shown efficacy in our novel argentine tango therapy and improves behavioral measures above the relevant MCID threshold, but it has not been established that the CTC are in the causal pathway that are responsible for these changes. Using neural measures from task fMRI, we have begun to characterize networks that have changed and quantify any associations with behavioral metrics. METHODS/STUDY POPULATION: Patients were randomly assigned to an IG (n=18), EG (n=18), or education contact control (n=14). Participants were assessed preintervention and postintervention for behavioral motor and cognitive measures and neurophysiologically with task based fMRI. In the task, participants performed a foot tapping task under both IG (tap their foot in previously learned rhythm) or EG (tap immediately after receiving a tactile cue on their hand) conditions. The fMRI data were preprocessed using AFNI and registered to MNI standard space. The brainnetome atlas was applied and the average time series of each region of interest (ROI) was used to increase the signal to noise ratio. The activation of these ROI with respect to the stimulus was modeled using GLM, and we estimated the area under the curve during the task blocks. A 1-way ANOVA analysis on these betas were performed between the pre and the post intervention time points and the ROIs that were above a significance of 0.95 were identified and corrected for multiple comparisons. The change in beta in all ROIs for each individual were calculated and then correlated with the changes in the behavioral data, to see which changes in ROI areas matched the best with the behavioral changes. RESULTS/ANTICIPATED RESULTS: The EG group showed significant changes only in the EG task in 2 areas—inferior frontal gyrus and inferior temporal sulcus. Correlating to the cognitive behavioral measures show reduced error from the Inferior frontal gyrus (corr&gt;0.5) best reflect changes in observed. There were no changes to either the STC or the CTC pathways. The IG group showed no changes behaviorally and showed no changes neurally as well. The control group showed no changes behaviorally, but neuronally certain DMN nodes, such as the precuneus and inferior temporal regions showed a significant change for both tasks. DISCUSSION/SIGNIFICANCE OF IMPACT: Addressing the damaged STC pathway directly through IG therapy may not be effective. The EG therapy may not be able to enhance the STC pathway. However, the therapy appears to utilize new areas in the frontal regions and correlates with positively with changes in spatial memory and balance tasks. Contrary to our hypothesis the CTC circuit was not upregulated for performance of the IG or EG task, but therapy may have enhanced recruitment of other cognitively engaged areas. The educational control group interestingly showed changes in the DMN network, which has been shown to be linked to attention during tasks blocks.

Sex Based Variability in Spatial Memory and Synaptic Transmission Occur Following Chronic Intermittent Hypoxia (CIH)

Sex is a key biological variable that has been shown to influence both physiology and disease. A growing body of research suggests that sex differences occur in respiration and brain physiology. This study examines how sex impacts changes in spatial memory and hippocampal synaptic plasticity following CIH, a model of sleep disordered breathing. Adult mice (&gt;P30) of both sexes were either exposed to 0 days (control) or 10 days of CIH. On the final four days of CIH, mice were trained and tested in a Barnes maze apparatus. Glutamatergic synaptic transmission in area CA1 was recorded in hippocampal brain slices harvested from control and CIH mice. CIH exposure increased the latency for locating the exit in both sexes during the probe trial; however, only females showed increased variability in performance. Following CIH, long term potentiation (LTP) was depressed in both male and female mice. While no sex differences were observed in LTP, our ongoing experiments suggest that paired pulse facilitation (PPF) after CIH increases in females.Support or Funding InformationThe University of Chicago, Faculty Diversity Career Advancement GrantThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Environmental enrichment protects spatial learning and hippocampal neurons from the long-lasting effects of protein malnutrition early in life

As early protein malnutrition has a critically long-lasting impact on the hippocampal formation and its role in learning and memory, and environmental enrichment has demonstrated great success in ameliorating functional deficits, here we ask whether exposure to an enriched environment could be employed to prevent spatial memory impairment and neuroanatomical changes in the hippocampus of adult rats maintained on a protein deficient diet during brain development (P0-P35). To elucidate the protective effects of environmental enrichment, we used the Morris water task and neuroanatomical analysis to determine whether changes in spatial memory and number and size of CA1 neurons differed significantly among groups. Protein malnutrition and environmental enrichment during brain development had significant effects on the spatial memory and hippocampal anatomy of adult rats. Malnourished but non-enriched rats (MN) required more time to find the hidden platform than well-nourished but non-enriched rats (WN). Malnourished but enriched rats (ME) performed better than the MN and similarly to the WN rats. There was no difference between well-nourished but non-enriched and enriched rats (WE). Anatomically, fewer CA1 neurons were found in the hippocampus of MN rats than in those of WN rats. However, it was also observed that ME and WN rats retained a similar number of neurons. These results suggest that environmental enrichment during brain development alters cognitive task performance and hippocampal neuroanatomy in a manner that is neuroprotective against malnutrition-induced brain injury. These results could have significant implications for malnourished infants expected to be at risk of disturbed brain development.

Cortical spreading depolarization increases adult neurogenesis, and alters behavior and hippocampus-dependent memory in mice

Cortical spreading depolarizations are an epiphenomenon of human brain pathologies and associated with extensive but transient changes in ion homeostasis, metabolism, and blood flow. Previously, we have shown that cortical spreading depolarization have long-lasting consequences on the brains transcriptome and structure. In particular, we found that cortical spreading depolarization stimulate hippocampal cell proliferation resulting in a sustained increase in adult neurogenesis. Since the hippocampus is responsible for explicit memory and adult-born dentate granule neurons contribute to this function, cortical spreading depolarization might influence hippocampus-dependent cognition. To address this question, we induced cortical spreading depolarization in C57Bl/6 J mice by epidural application of 1.5 mol/L KCl and evaluated neurogenesis and behavior at two, four, or six weeks thereafter. Congruent with our previous findings in rats, we found that cortical spreading depolarization increases numbers of newborn dentate granule neurons. Moreover, exploratory behavior and object location memory were consistently enhanced. Reference memory in the water maze was virtually unaffected, whereas memory formation in the Barnes maze was impaired with a delay of two weeks and facilitated after four weeks. These data show that cortical spreading depolarization produces lasting changes in psychomotor behavior and complex, delay- and task-dependent changes in spatial memory, and suggest that cortical spreading depolarization-like events affect the emotional and cognitive outcomes of associated brain pathologies.