The Effects And Mechanisms Of Dopamine On Gamma Oscillations In Rat Hippocampal

Background The hippocampal neural network gamma oscillations(gamma,30-80Hz)are produced by the interaction of excitatory intermediate neurons and inhibitory pyramidal neurons,which are closely related to higher brain functions such as learning and memory.Dopamine(DA)is one of the most important central nervous system transmitters currently studied.It mainly acts on dopamine receptors and is involved in various regulation in the body.Gamma oscillations were enhanced by the use of dopamine in vitro brain slices.The intracellular mechanism remains unclear.This study provides a new theoretical basis for elucidation of brain physiological function and the mechanism of brain diseases.Objectives The aim of this study was to determine the effects and mechanisms of acute dopamine administration on the hippocampal network gamma oscillations in vitro models.Methods Induction and recording of Gamma oscillation: The 3-4 week-old SD rats were weighed and 10% of chloral Hydrate(0.4mL/100g)was injected into the abdomen for anesthesia.When the metatarsal reflex disappears,we need open the thoracic cavity.Cardiac perfusion was performed with precooled sections of cerebrospinal fluid.The whole brain tissue was stripped away.It need add the mixture(95%O2+5%CO2)to a slice of the cerebrospinal fluid.LEICA VT microtome was used to slice brain horizontally.The thickness of brain slice was 400?m.Circulating perfusion of artificial cerebrospinal fluid in the incubation tank(temperature 28-32 degrees,flow rate of 3-4ml,ph to 7.35-7.45)and continuous access to mixed gases(95%O2+5%CO2).The brain slices are then transferred to the recording slot.After incubation for one hour,glass electrodes were placed under the CA3 region of the hippocampus on both sides to record the field potential.Gamma oscillations were induced by adding Kainate(KA)to the artificial cerebrospinal fluid.When the gamma rhythm was stabilized for 20 minutes,the dopamine receptor blocker? NMDA receptor blocker ?PKA inhibitor ?AKT inhibitor ?GSK3 inhibitor ?MAPK inhibitor or RTK inhibitor was added to explore the pathway of dopamine signal transduction in cells.All data were statistically analyzed using Sigmastat,and the statistical results were indicated by mean standard error.When P<0.05,the statistical results were considered significant.Results 1.Freshly prepared DA(200?M)enhanced KA-induced gamma rhythm in the hippocampal CA3 region of rats. 2.Serine/threonine kinase(AKT)inhibitor TCBN and NMDA receptor blocker D-AP5 did not block the enhanced effect of DA on gamma oscillations. 3.D2 receptor blocker Raclopride,tyrosine kinase(RTK)inhibitor UNC569,camp-dependent kinase(PKA)inhibitor H89,phosphatidylcholine-3 kinase(PI3K)inhibitor Wortmannin and glycogen synthase kinase 3?(GSK3?)inhibitor SB415286 can partially block the enhanced effect of da on gamma Oscillation.4.D1 receptor blocker SCH23390 and extracellular signal-related kinase(ERK)inhibitor U0126 completely blocked the enhanced effect of DA on gamma oscillations.Conclusions Our results indicate that acute application of DA significantly increases the KA-induced gamma oscillations,primarily by activating the DR/RTK/ERK signaling pathway and partially through the DR/PKA/PI3 K pathway.