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Browsing by Subject "Novel Object Recognition"
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Item Early-life trauma alters hippocampal function during an episodic memory task in adulthood(2017-05-02) Janetsian-Fritz, Sarine S.; Lapish, Christopher; Sangha, Susan; Goodlett, Charles; Neal-Beliveau, BethanyEarly life trauma is a risk factor for a number of neuropsychiatric disorders, including schizophrenia (SZ) and depression. Animal models have played a critical role in understanding how early-life trauma may evoke changes in behavior and biomarkers of altered brain function that resemble these neuropsychiatric disorders. However, since SZ is a complex condition with multifactorial etiology, it is difficult to model the breadth of this condition in a single animal model. Considering this, it is necessary to develop rodent models with clearly defined subsets of pathologies observed in the human condition and their developmental trajectory. Episodic memory is among the cognitive deficits observed in SZ. Theta (6-10 Hz), low gamma (30-50 Hz), and high gamma (50-100 Hz) frequencies in the hippocampus (HC) are critical for encoding and retrieval of memory. Also, theta-gamma comodulation, defined as correlated fluctuations in power between these frequencies, may provide a mechanism for coding episodic sequences by coordinating neuronal activity at timescales required for memory encoding and retrieval. Given that patients with SZ have impaired recognition memory, the overall objectives of these experiments were to assess local field potential (LFP) recordings in the theta and gamma range from the dorsal HC during a recognition memory task in an animal model that exhibits a subclass of symptoms that resemble SZ. In Aim 1, LFPs were recorded from the HC to assess theta and gamma power to determine whether rats that were maternally deprived (MD) for 24-hrs on postnatal day (PND 9), had altered theta and high/low gamma power compared to sham rats during novel object recognition (NOR). Brain activity was recorded while animals underwent NOR on PND 70, 74, and 78. In Aim 2, the effects of theta-low gamma comodulation and theta-high gamma comodulation in the HC were assessed during NOR between sham and MD animals. Furthermore, measures of maternal care were taken to assess if high or low licking/grooming behaviors influenced recognition memory. It was hypothesized that MD animals would have impaired recognition memory and lower theta and low/high gamma power during interaction with both objects compared to sham animals. Furthermore, it was hypothesized that sham animals would have higher theta-gamma comodulation during novel object exploration compared to the familiar object, which would be higher than the MD group. Measures of weight, locomotor activity, and thigmotaxis were also assessed. MD animals were impaired on the NOR task and had no change in theta or low/high gamma power or theta-gamma comodulation when interacting with the novel or familiar object during trials where they performed unsuccessfully or successfully. However, higher theta and gamma power and theta-gamma comodulation was observed in sham animals depending on the object they were exploring or whether it was a successful or unsuccessful trial. These data indicate altered functioning of the HC following MD and a dissociation between brain activity and behavior in this group, providing support that early life trauma can induce cognitive and physiological impairments that are long-lasting. In conclusion, these data identify a model of early life stress with a translational potential, given that there are points of contact between human studies and the MD model. Furthermore, these data provide a set of tools that could be used to further explore how these altered neural mechanisms may influence cognition and behavior.Item Effects of 50 mg/kg EGCG Treatment of Ts65Dn Down Syndrome Mice on Novel Object Recognition(Office of the Vice Chancellor for Research, 2016-04-08) Stringer, Megan; Roper, Randall J.; Goodlett, Charles R.; Delgado Taboada, Maria FatimaDown syndrome (DS) is caused by trisomy of chromosome 21, and affects 1/700 live births. DYRK1A, a gene found in three copies in humans with DS and Ts65Dn DS mice, has been linked to alterations in morphology and function of the brain resulting in cognitive impairment. Epigallocatechin-3-gallate (EGCG), an inhibitor of DYRK1A activity, has been proposed as a possible treatment. Using the Ts65Dn DS mouse model, we examined the effects of EGCG treatment on on hippocampal dependent learning and memory using a novel object recognition task (NOR). A previous study analyzing the effects of EGCG at a concentration 30mg/kg/day showed that there was no genotype or treatment effect in the NOR task when treatment is continuous through testing. In this study, the mice were given 50 mg/kg/day EGCG or water via their drinking water starting at 3 weeks of age. The mice were handled two days before testing and then underwent a series of behavioral tests including NOR. They underwent testing at 3 weeks and 7 weeks of treatment. Treatment was continuous throughout behavioral testing. NOR consists of a box with the objects placed diagonally from each other. The mice underwent 3 days of testing with 15 minute sessions per day consisting of habituation, exposure, and test day, all of which were recorded and analyzed to determine time spent exploring novel object in relation to familiar. The amount of time spent at each object was scored by three independent scorers, blind to genotype and treatment. We observed no genotype or treatment effect at either the 3 or 7 week test results, which is consistent with our past results. A higher dose, along with a more sensitive test of recognition memory, may be needed in order to show a treatment effect on the Ts65Dn mice.Item The Effects on Novel Object Recognition by Genetic Reduction of Dyrk1a to Normal Levels in Otherwise Trisomic Ts65Dn Down Syndrome Mice(Office of the Vice Chancellor for Research, 2016-04-08) Parker, Abigail; Stringer, Megan; Goodlett, Charles R.; Roper, Randall J.Down syndrome (DS) is caused by the triplication of chromosome 21 (Hsa21) in humans and is the leading genetic cause of intellectual disability. Ts65Dn mice are used as a model of Down syndrome, with about half of the genes in three copies of those triplicated on Hsa21 in individuals with DS. Overexpression of Dyrk1a, a gene found to be triplicated in both individuals with DS and Ts65Dn mice, has been linked to learning and memory deficits. Mice are naturally drawn to novel objects. As such, the Novel Object Recognition (NOR) test can be used to determine if Ts65Dn as compared to normal mice are impaired in discriminating novel objects from previously explored objects. In our current study, Ts65Dn mice with two copies of Dyrk1a were compared to Ts65Dn and euploid mice using the NOR task. We hypothesize that Ts65Dn, Dyrk1a+/- mice would perform as well as euploid mice on the NOR task, given that they both have two copies of Dyrk1a. Our preliminary results indicate that a genotype effect between trisomic mice and euploid mice is not observed. Additionally, Ts65Dn control mice and euploid control mice have a higher discrimination ratio than their Dyrk1a knockdown counterparts. These results indicate that overexpression of Dyrk1a may not be entirely responsible for deficits in learning and memory.