Effect And Mechanism Of Dopamine On Hippocampal Gamma Oscillation In Animal Model Of Schizophrenia

Background Heterozygous reeler mice(reelin haploinsufficiency)have many neurochemical and behavioral similarities with schizophrenia and provide a useful animal model to study neuropsychiatric disorders such as schizophrenia.There is evidence that reelin signaling defects affect the midbrain marginal dopaminergic pathway in a specific way.We investigated the effects of dopamine(DA)on ? oscillations in the CA3 region of hippocampal slices of heterozygous reeler mice and its possible mechanism.Objective To investigate the heterozygous reeler mouse using as a model of schizophrenia,whether there are disorders of the dopamine system function in the hippocampus and its possible mechanisms.To investigate the relationship between dopamine system dysfunction of schizophrenia and reelin signaling pathway,providing new ideas for revealing the pathological mechanism of dopamine system dysfunction and the development of antipsychotic drugs in schizophrenia.Method 1.Behavioral experiment Wild-type and heterozygous reeler mice were tested for hippocampal spatial memory using the Y-maze and the Morris water maze.2.In vitro hippocampal slices of extracellular field potential record Establish a constant temperature interface bath perfusion system,intraperitoneal injection of 10% chloral hydrate(0.3-0.4ml / 100g)anesthetized mice.The thoracic cavity was opened layer by layer,exposed the heart,cut off the right atrial appendage.Pre-cooling(-4?)of 30 ml slice cerebrospinal fluid(p H: 7.35-7.5)was perfused in the left ventricle.The removed brain tissue was sliced horizontally using a vibrating microtome to obtain slices containing hippocampus.After the slice is completed,the slice is placed on the incubation tank,and the perfusion of cerebrospinal fluid is incubated for about one hour.The slices were placed in the recording slot.The extracellular microelectrode method was used to record the ? oscillations in the CA3 region of the hippocampal slices.After reaching the steady state,inhibitors or agonists of different channel receptors were added to observe the effects of the drugs on ? oscillations,revealing the mechanism..3.Statistical Analysis All statistics are made using IBM SPSS Statistics 22.0 software.After the data were normalized by Shapiro-Wilk,parametric or non-parametric tests were selected.Parameter test the statistical results are expressed as means ± standard error.Nonparametric test results are expressed as the median ± quartile spacing.Test level: ? = 0.05.Result(1)There was no difference in hippocampal-dependent learning and memory.(2)DA enhanced the ?-oscillations in wild-type mice,but heterozygous reeler mice were not sensitive to DA.(3)Blocking NMDAR partially blocked the effect of DA on wild-type mice.Blocking the NMDAR partially restored the response of heterozygous reeler mice to DA.(4)After blocking PI3 K,the effect of DA on wild-type mice did not change,but blocking PI3 K completely restored the heterozygote reeler mouse to DA.Conclusion Our results reveal that there is a dysfunction of DA system in heterozygous reeler mice,whereas the dysfunction of DA system is associated with over-activation of NMDA receptor.