Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: Implications for ischemia and Huntington's disease
Striatal spiny neurons and cholinergic interneurons express differential ionotropic glutamatergic responses and vulnerability: Implications for ischemia and Huntington's disease
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DOI：
10.1002/ana.410430506
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发表时间：
1998-05-01
影响因子：
11.2
通讯作者：
Bernardi, G
中科院分区：
文献类型：
--
作者：
Calabresi, P;Centonze, D;Bernardi, G
纹状体棘状神经元在亨廷顿病（HD）和缺血中选择性地脆弱，而纹状体的大棘状（LA）胆碱能中间神经元在这些病理条件下幸免。我们已经调查了是否有不同的敏感性离子型amatergic激动剂可能占这种差异的脆弱性。从形态学鉴定的纹状体棘神经元和LA获得细胞内记录。胆碱能中间神经元，使用大鼠脑片制备。这两种纹状体神经元亚型具有显著不同的内在膜特性。这两种亚型的兴奋性突触后电位皮质刺激反应：这些电位，但是，有不同的时间过程和药理学的两类细胞。有趣的是，膜去极化和内向电流产生的外源性谷氨酸受体激动剂（AMPA，红藻氨酸，和NMDA）显着较大的棘神经元比LA interneurons。此外，浓度的激动剂产生可逆的膜变化LA interneurons引起不可逆的去极化多刺细胞。我们的数据表明，不同的生理反应诱导的离子型谷氨酸受体的激活可能占纹状体神经元在缺血和HD的细胞类型特异性的脆弱性。
Striatal spiny neurons are selectively vulnerable in Huntington's disease (HD) and ischemia, whereas large aspiny (LA) cholinergic interneurons of the striatum are spared in these pathological conditions. We have investigated whether a different sensitivity to ionotropic glutamatergic agonists might account for this differential vulnerability. Intracellular recordings were obtained from morphologically identified striatal spiny neurons and LA. cholinergic interneurons by using a rat brain slice preparation. The two striatal neuronal subtypes had strikingly different intrinsic membrane properties. Both subtypes responded to cortical stimulation with excitatory postsynaptic potentials: these potentials, however, had a different time course and pharmacology in the two classes of cells. Interestingly, membrane depolarizations and inward currents produced by exogenous glutamate receptor agonists (AMPA, kainate, and NMDA) were remarkably larger in spiny neurons than in LA interneurons. Moreover, concentrations of agonists producing reversible membrane changes in LA interneurons caused irreversible depolarizations in spiny cells. Our data suggest that the different physiological responses induced by the activation of ionotropic glutamate receptors may account for the cell type-specific vulnerability of striatal neurons in ischemia and HD.