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首页> 外文学位 >The role of adenosine A(2) receptors in hippocampal synaptic transmission between the Schaffer collateral pathway and CA1 pyramidal neurons.
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The role of adenosine A(2) receptors in hippocampal synaptic transmission between the Schaffer collateral pathway and CA1 pyramidal neurons.

机译：腺苷A（2）受体在Schaffer侧支通路和CA1锥体神经元之间海马突触传递中的作用。

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摘要

Adenosine receptor activation can markedly alter levels of synaptic transmission. Reductions in neurotransmission have been reported in response to agonist-mediated adenosine A1 receptor activation. However, the implications of A2 receptor activation on synaptic transmission have not been well explored. The focus of this thesis was to examine the role adenosine A 2 receptors play in the efficacy of excitatory glutamatergic neurotransmission in the Schaffer collateral-CA1 pathway in the rat transverse hippocampal slice.;Activation of adenosine A2 receptors with the A2 agonist DPMA (N6-[2-(3,5-Dimethyoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine) enhanced normal synaptic transmission by selectively increasing AMPA receptor responses. The A2a receptor agonist, CGS21680, had no effect on synaptic transmission suggesting that the effects of DPMA were through activation of A2b receptors. Both paired stimulation and isolated NMDA receptor responses before and during DPMA exposure showed that enhancement was not a result of presynaptic modulation. The intracellular pathways mediating the effects of A2 receptors were also examined. Inhibition of the cyclic adenosine monophosphate (cAMP)-dependent kinase (PKA) and calcium (Ca 2+) chelation blocked the effect of DPMA, while calcium/calmodulin kinase blockade significantly reduced it.;The level of A2 activation significantly modulated the level of tetanus induced long term potentiation (LTP). This effect was occluded by prior tetanic stimulation. A2 receptor blockade by DMPX and 8-(p-Sulfophenyl)theophylline prevented LTP. Either forskolin or 8-Bromo-cAMP reconstituted LTP during A2 receptor blockade, but not 1,9-dideoxy-forskolin, an inactive forskolin analog.;A slow onset NMDA-independent LTP could be induced by a tetanus during perfusion of DPMA with the NMDA blocker AP5 (50 mum). Blockade of L-type Ca channels with nifedipine (10 muM) had no effect on normal synaptic transmission but reduced NMDA-independent LTP. Very little NMDA-independent LTP could be induced following prior saturation of NMDA-dependent LTP indicating that both forms of LTP are ultimately convergent on a common mechanism, presumably the postsynaptic AMPA receptor response.;The hippocampus plays an important role in forming long term memories. LTP has been proposed as the mechanism that underlies memory formation. This work shows that adenosine A2 receptors can play a significant role in manipulation of neurotransmission in the hippocampus. Because the concentration of extracellular adenosine is greatly increased during neuronal activity, this purine may also play a critical modulatory role in memory formation.
机译：腺苷受体激活可以明显改变突触传递的水平。已经报道了对激动剂介导的腺苷A1受体活化的响应，神经传递的减少。但是，尚未很好地探讨A2受体激活对突触传递的影响。本论文的重点是研究腺苷A 2受体在大鼠海马横断面Schaffer侧支CA1途径中兴奋性谷氨酸能神经传递的功效中的作用。; A2激动剂DPMA激活腺苷A2受体（N6- [2-（3,5-二甲氧基苯基）-2-（2-甲基苯基）-乙基]腺苷）通过选择性增加AMPA受体反应来增强正常的突触传递。 A2a受体激动剂CGS21680对突触传递没有影响，表明DPMA的作用是通过激活A2b受体。在DPMA暴露之前和期间，成对的刺激和孤立的NMDA受体响应均显示增强不是突触前调节的结果。还检查了介导A2受体作用的细胞内途径。抑制环磷酸腺苷（cAMP）依赖性激酶（PKA）和钙（Ca 2+）螯合可阻断DPMA的作用，而钙/钙调蛋白激酶的阻断则显着降低DPMA的作用。破伤风诱发的长期增强（LTP）。先前的强直性刺激无法掩盖这种效果。 DMPX和8-（对-磺基苯基）茶碱对A2受体的阻滞可防止LTP。在A2受体阻滞过程中，福司可林或8-Bromo-cAMP均会重建LTP，而无效的福司可林类似物1,9-二脱氧-福司可林则不能; NMDA阻滞剂AP5（50毫米）。硝苯地平（10μM）阻断L型Ca通道对正常的突触传递没有影响，但减少了非NMDA依赖性LTP。先前的NMDA依赖性LTP饱和后，几乎不会诱导NMDA依赖性LTP，这表明这两种形式的LTP最终都收敛于一个共同的机制，大概是突触后AMPA受体反应。；海马在形成长期记忆中起重要作用。已经提出了LTP作为构成存储器形成基础的机制。这项工作表明，腺苷A2受体可以在海马神经传递的操纵中发挥重要作用。因为在神经元活动期间细胞外腺苷的浓度大大增加，所以该嘌呤在记忆形成中也可能起关键的调节作用。

著录项

  • 作者

    Kessey, Kofi.;

  • 作者单位

    Northwestern University.;

  • 授予单位 Northwestern University.;
  • 学科 Biology Neuroscience.
  • 学位 Ph.D.
  • 年度 1999
  • 页码 130 p.
  • 总页数 130
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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