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A Study On The Learning And Memory Of NMDA Receptor In The Marginal Division

Posted on:2004-04-16Degree:DoctorType:Dissertation
Country:ChinaCandidate:C K LiFull Text:PDF
GTID:1100360092499124Subject:Cell biology
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The MrD, firstly discovered by us with neuroanatomical and immunohistochemical methods, was a flat, pan-shaped structure at the caudomedial margin of the neostriatum and surrounding the rostrolateral edge of the globus pallidus in brains of the rat[12], cat[12], monkey[13] and human. It consists of fusiform neurons with intensely expressed neuropeptides in the fibers, terminals, and neuronal somata. Functional connections between the MrD and hippocampus, amygdala and the basal nucleus of Meynert were identified by c-Fos expression method[14]. Other neuroscientists also confirmed the existence of the MrD in the neostriatum with immunohistochemical or physiological method[14,15]'. Heimer and his colleagues described the MrD as one part of the ventral striatal areas.In order to investigate the electrophysiology property of the NMDAR, we observe the single channel properties of NMDA receptors in the acutely dissociated neurons of the marginal division in the rat striatum, and to compare them to those of NMDAR in the hippocampus, cortox and cerebellum. And then we aim to investigate the effects of the NMDA receptor antagonists Ketamine (KTM) on the behaviors of learning and memory of rats marginal division with the Morris water-maze task. Furthermore we devise and make the model of senile SD rats whose were under intracranial administration of the L-Glu/KTM.. Lastly we observe the human in the fMRI bore during they execution of the digit working memory task. From all of above means we can get a systemic test to explore the functional principle of learning and memory in the human MrD.Methods and results1. The patch clamp experiment: The cell-attached and inside-out configurations of the patch-clamp techniques were used to investigate single channel properties of NMD A receptors in the actuely dissociated neurons of the marginal division in the rat striatum, recording the current amplitude.long/short term opening/closing times indexes and the effects of incitants and agonists of the NMD A receptors on those parameters. We find that Two types of conductance of 42pS and 20pS were recorded, the 42pS was the advantaged conductance. They expressed two kinds of channel activities: burst and cluster, the bigger conductance channels show more cluster opening than cluster opening. The effects of the incitants and agonist on the NMDA receptors of the marginal division in the rat striatum is different(P<0.05).2. The test of space learning and memory task of young SD rats administrated by KTM (i.p.) in the morris water maze: The rats were divided into six groups as following: the control group, the KTM group, the marginal division (MrD) group, the fimbria/fornix (FF) group, the KTM+MrD group and the KTM+FF group. The NMDA receptor antagonist KTM (2.5mg/kg) was injected intraperitoneally the KTM, KTM+MrD and KTM+Ff groups respectively; the FF of rats in the FF group were transected and the MrD of the rats in MrD group were microinjected with kainic acid. Spatial probe exeperiment were carried out with the purpose of testing the ability of information storing. The mean escape latencies of the rats were measured within 5 days. The numbers of crossing platform of each groups were counted. The results as following: (1) The experiment groups are distinct different from the control group (P<0.05, control vs other groups), the abilities of spatial learning and memory of experiment groups rats are declined. (2) There are no distinct different between MrD group and FF group, or between KTM+ MrD group and KTM+ FF group(P: 0.46 and 0.356). (3)There are distinct different between the KTM group and KTM+MrD/KTM+FF groups(P: 0.047 and 0.038), or no different between KTM and MrD/FF groups respectively(P: 0.846 and 0.353). (4) No distinct different between KTM group and MrD/FF group(P: 0.846 and 0.353). The groups interrupted with KTM showed a more stereotyped, thigmotaxic behaviour, swimming predominantly around the previous site of platform than other groups. So it was suggested that the MrD of the neostriatum play...
Keywords/Search Tags:Patch clamp, Morris water maze, cannulation, L-glutamic acid, Marginal division of the neosthatum, striatum, brain, human, learning, working memory, functional magnetic resonance imaging, NMDAR, ketamine, dull pain, sharp pain
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