GIRK1在颞叶癫痫大鼠海马齿状回中的表达及其意义

目的探讨GIRK1在颞叶癫癎大鼠海马齿状回的表达及其意义.方法112只雄性SD大鼠随机分为实验组(n=70)与对照组(n=42),同时建立海人藻酸(KA)颞叶癫模型.选取KA腹腔注射后3、6、12、24、48 h,7、30 d为研究的时间点.用原位杂交法及免疫组织化学法检测海马齿状回GIRK1 mRNA及蛋白的表达.结果实验组大鼠海马齿状回GIRK1 mRNA表达在致癎后6 h较对照组减少,而在致癎后至7～30 d较对照组增高.结论在颞叶癫癎的不同时期海马齿状回GIRK1表达的变化反映出颞叶癫癎的复杂性.     

Integrity of perforant path fibers and the frequency of action potential independent excitatory and inhibitory synaptic events in dentate gyrus granule cells.

Whole-cell voltage clamp recordings in 400 microns thick hippocampal slices revealed discrete excitatory and inhibitory postsynaptic currents which persisted at synapses on granule cells following abolition of action potentials with 1 microM tetrodotoxin (TTX). The conductances associated with excitatory amino acid and GABAA receptor mediated events had mean peaks of 200 and 800 pS, and decayed monoexponentially with time constants of 5.6 and 5.3 ms. At a holding potential close to the normal resting membrane potential of granule cells (-80 to -90 mV), the frequency of glutamate/aspartate mediated spontaneous excitatory postsynaptic currents (sEPSCs) was decreased from 2.04 Hz in slices cut parallel to the plane of the perforant path to 0.87 Hz in slices cut in a plane that disrupted the distal perforant path fibres, suggesting that presynaptic integrity influences the rate of action potential independent neurotransmitter release. The orientation of the slicing had no effect on the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs).     

Anti-S-100 Serum blocks long-term potentiation in the hippocampal slice

S-100 is a calcium-binding, glial protein which has been shown to be involved in behavioral learning and memory tasks. Long-term potentiation (LTP) in the hippocampus is a long-lasting enhancement of synaptic efficacy evoked by repetitive afferent stimulation. When anti-S-100 serum is applied by pressure ejection onto the stratum radiatum of area CA1 of the hippocampal slice, the amplitude of the extracellularly recorded population spike is not affected. However, repetitive stimulation of the afferents during S-100 application failed to produce LTP. At a distant site in the same slice, LTP occurs normally. Preimmune normal rabbit serum had no effect on the development of LTP. It appears that S-100 protein is involved in the establishment of LTP.     

The Relationship Between Quantitative MRI and Neuropsychological Functioning in Temporal Lobe Epilepsy

Summary: Purpose: Quantitative MRI techniques provide an unparalleled opportunity to examine in vivo the relationship between the extent and laterality of hippocampal pathology and associated neuropsychological deficits. The purpose of this study was to examine the nature of the relationship between quantitative measures of hippocampal pathology and neuropsychological measures, using a multivariate approach. Methods: We examined the relationship between two MRI measures of hippocampal structure; hippocampal volumes (HCvol) and T2 relaxation times (HCT2), and memory performance, in 80 presurgical temporal lobe epilepsy patients. Results: As a group, patients with left hippocampal sclerosis (LHS) performed more poorly that those with right hippocampal sclerosis (RHS) on immediate and delayed prose recall. In the group as a whole, right hippocampal volume was significantly correlated with the delayed recall of a complex figure. None of the verbal memory test scores were significantly correlated with the right or left HCvol or HCT2 measures. However, stepwise multiple regression analyses indicated that up to a third of the variation in specific test scores could be explained by the quantitative MRI hippocampal measures in conjunction with chronological age, and age at onset of habitual epilepsy. Left hippocampal measures explained 24% of the variance in the story-recall tasks, while right hippocampal measures explained 18% of the variance in a design-learning task and 32% of the variance in a figure-recall task. Conclusions: Our results provide some support for the lateralised model of material specific memory deficits, but suggest that a number of demographic and epilepsy-related factors may interact with the extent and laterality of hippocampal pathology in shaping the nature of the associated neuropsychological deficit.     

Temporal lobe epilepsy with varying severity: MRI study of 222 patients

MRI was performed in 222 consecutive adult patients with temporal lobe epilepsy of varying severity from January 1991 to May 1993. The diagnosis of hippocampal sclerosis was established visually by three independent observers. The accuracy of visual assessment of hippocampal asymmetry was compared with volumetric measurements. Neuropathological correlations were obtained in 63 patients with refractory seizures. Temporal lobe abnormalities were observed in 180 patients (81 %) as follows: hippocampal sclerosis in 122 (55 %); developmental abnormalities in 16 (7.2 %); tumours in 15 (6.8 %); scars in 11 (5 %); cavernous angiomas in 10 (4.5 %); miscellaneous lesions in 6. MRI was normal or showed unrelated changes in 42 patients (19 %). Visual assessment correctly lateralised hippocampal sclerosis in 79 of the 84 patients measured (94 %). Temporal lobectomy confirmed the MRI data (side and aetiology) in all 63 operated patients. Patients with normal MRI had an older age of seizure onset and were more often drug-responsive than patients with hippocampal sclerosis. MRI showed temporal lobe abnormalities in 81 % of epileptic patients with varying severity with good neuropathological correlation. Patients with normal MRI had a less severe form of the disease. Received: 19 August 1996 Accepted: 13 November 1996     

Direct excitatory effects of neuropeptide Y (NPY) on rat hippocampal neurones in vitro

Intracellular recordings from granule cells of the rat dentate gyrus show neuropeptide Y (NPY) applied by pressure ejection from pipettes containing 1.2-12 microM by pressures of less than 200 kPa for 1-5 s in duration to consistently evoke membrane depolarisations accompanied by a reduction in membrane resistance. The depolarisations were accompanied by an increase in excitability. Since the depolarisations evoked by NPY were not attenuated by either tetrodotoxin or kynurenic acid a direct excitatory action of NPY is postulated.     

急性缺氧对大鼠海马神经元钙激活钾通道的作用

目的:本实验采用膜片钳单通道技术研究缺氧条件下对培养新生大鼠海马神经元钙激活钾通道的作用;方法:取1 ～3天的SD大鼠海马神经元组织,制成细胞悬液,加入含80 %DMEM(dulbecco' s modified eagle' s medium)、20 %小牛血清培养基进行培养,将培养3 ～5天的形态典型的神经元置于对称性高钾溶液中,用膜钳技术记录单通道电流,其通道电流通过膜片钳放大器(CEZ -2200)放大,滤波(3KHz)后,经A/D、D/A转换器输入计算机,采用pClamp6 .0 .6软件采样分析;结果:在细胞贴附式下,应用氰化钠(20μmol/L)造成细胞急性缺氧,在缺氧早期(5 ～20 min)通道开放概率增加(P<0 .01或P<0 .05 ,n=5) ,而缺氧后期(20 ～30 min) ,通道开放概率明显降低,表明缺氧时间对通道的开放概率有明显影响。结论:缺氧早期神经元钙激活钾通道有自身激活作用,当钙激活钾通道激活时,钾离子外流增加,产生膜的复极化,使去极化不易产生,从而稳定细胞膜及降低细胞的兴奋性,这可能是缺氧早期神经元自身的一种代偿机制。     

Smaller hippocampal volume in patients with recent-onset posttraumatic stress disorder.

BACKGROUND: Previous structural magnetic resonance (MR) research in patients with posttraumatic stress disorder (PTSD) has found smaller hippocampal volumes in patients compared with control subjects. These studies have mostly involved subjects who have had PTSD for a number of years, such as war veterans or adult survivors of childhood abuse. Patients with recent-onset PTSD have rarely been investigated. To our knowledge only one other study has investigated such a group. The aim of this study was to compare hippocampal volumes of patients with recent onset PTSD and nontrauma-exposed control subjects. METHODS: Fifteen patients with PTSD, recruited from an accident and emergency department, were compared with 11, non-trauma-exposed, healthy control subjects. Patients underwent a structural MR scan soon after trauma (mean time = 158 +/- 41 days). Entire brain volumes, voxel size 1 x 1 x 1 mm, were acquired for each subject. Point counting and stereology were used to measure the hippocampal and amygdala volume of each subject. RESULTS: Right-sided hippocampal volume was significantly smaller in PTSD patients than control subjects after controlling for effects of whole brain volume and age. Neither left nor total hippocampal volume were significantly smaller in the PTSD group after correction. Whole brain volume was also found to be significantly smaller in patients. There were no differences in amygdala or white matter volumes between patients and control subjects. CONCLUSIONS: This result replicates previous findings of smaller hippocampal volumes in PTSD patients, but in an underinvestigated population, suggesting that either smaller hippocampal volume is a predisposing factor in the development of PTSD or that damage occurs within months of trauma, rather than a number of years. Either of these two hypotheses have significant implications for the treatment of PTSD. For instance, if it could be shown that screening for hippocampal volume may, in some cases, predict those likely to develop clinical PTSD.     

Dopamine D2 receptor expression in hippocampus and parahippocampal cortex of rat,cat, and human in relation to tyrosine hydroxylase-immunoreactive fibers

A detailed study comparing the distribution of D2 receptors and tyrosine hydroxylase-immunoreactive fibers in the hippocampus and parahippocampal cortices of the rat, cat, and human was conducted. The distribution of [¹²⁵I]epidepride binding to D2 receptors along the transverse and longitudinal axes of the hippocampus and parahippocampus differed among the species. In rat hippocampus, the number of sites was highest in septal portions of lacunosum-moleculare of CA1 and stratum moleculare of the subiculum. Virtually no binding to D2 receptors existed in the temporal hippocamps. For the cat hippocampus, the highest binding existed in the inner one-third of the molecular layer of the dentate gyrus (DG). There were also significant numbers of D2 receptors in strata radiatum and oriens of the CA subfields, with almost undetectable levels in lacunosum moleculare and subiculum. The number of sites was higher in the septal than temporal hippocampus. In the human hippocampus, highest binding was observed in the molecular layer of DG and the subiculum, with lower levels in strata oriens and lacunosum-moleculare of CA3, and very low binding in CA1. The histochemical demonstration of the pattern of mossy fibers revealed an organization complementary to that of D2 receptors in cat and human. In none of the species was there significant expression of D2 receptors in the entorhinal cortex, except in the caudal extreme of this region in the rat. In that region a trilaminar pattern was exhibited that continued into the perirhinal cortex. A trilaminar pattern of D2 receptor expression was observed in the perirhinal cortex of all species, with the highest values in the external and deep laminae and low expression in the middle laminae. The organization of dopamine fibers was assessed by comparing the distribution of tyrosine hydroxylase-positive and dopamine β-hydroxylase-immunoreactive fibers in these same regions. It revealed consistent mismatches between the pattern of D2 receptor expression and dopaminergic innervation in all three species. The implications for this mismatch are discussed. It is hypothesized that the distribution of D2 receptors, and not of dopamine fibers, determines what neural systems dopamine influences in the hippocampal complex. © 1994 Wiley-Liss, Inc.     

Linear relationship between the maintenance of hippocampal long-term potentiation and retention of an associative memory.

The hypothesis that the maintenance or decay of an associative memory trace after an extended retention interval is a function of the residual strength of the synapses originally strengthened during learning was examined in a classical conditioning paradigm in which high-frequency stimulation of a hippocampal input--the medial perforant path--served as a conditioned stimulus. Rats received perforant path stimulus-foot shock pairings while engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever pressing was the behavioral measure of learning and retention of the association. Stimulus trains to the perforant path at an intensity above the threshold for eliciting a population spike induced long-term potentiation of synaptic transmission in the dentate gyrus. Synaptic potentials recorded extracellularly in the dentate gyrus were subsequently monitored for 31 days to examine quantitatively the decay of synaptic potentiation, a period after which retention of the learned association was assessed. All rats learned the association to a similar extent and displayed equivalent amounts of long-term potentiation by the end of conditioning. A slowly decaying function of synaptic potentiation was observed in remembering rats, i.e., rats with high retention performance after the 31-day learning-to-retention interval, while forgetting was associated with a rapid decay of long-term potentiation. Behavioral performance at the long-term memory test was linearly correlated with the amplitude of long-term potentiation maintained just prior to the retention test. The results favor the hypothesis that long-term associative memory depends, at least in part, on the maintenance of elevated synaptic strengths in the pathway activated during learning and suggest a role for the lasting component of long-term potentiation in the maintenance of memory.