de Lacalle S, Kulkarni S, Wiley R G
Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
Eur J Neurosci. 1998 Mar;10(3):1054-62. doi: 10.1046/j.1460-9568.1998.00116.x.
The present experiments were designed to determine the effect that lesions of the basal forebrain cholinergic system exert on cholinergic interneurons within the entorhinal cortex (EC) in the rat. Unilateral infusion of 192 IgG-saporin into the nucleus of the horizontal diagonal band of Broca (HDB) decreased the number of ipsilateral choline acetyltransferase immunoreactive (ChAT-ir) neurons by 54%. Two-four weeks after the lesion, the ipsilateral EC exhibited a moderate but significant loss of ChAT-ir fibres and interneurons. Adjacent sections revealed a parallel loss of vasoactive intestinal polypeptide (VIP) immunoreactivity. Cell counts in the cingulate cortex were unaffected, suggesting that this effect was indeed specific to the main target area for HDB neurons. Ibotenic acid lesions also induced a significant 36% decrease in the number of cholinergic neurons in the ipsilateral HDB, and disappearance of ChAT terminals in the EC, whereas the number of ChAT-ir neurons in the EC was unchanged. Since ibotenic acid affects all cells and not only cholinergic ones, our results suggest that the specific degeneration of cholinergic neurons in the HDB after 192 IgG-saporin treatment could be inducing transsynaptic effects on their targets. Injections of 192 IgG-saporin directly into the EC also lesioned the cholinergic projection from the HDB, but had no effect on the intrinsic population. Eight weeks after immunolesion, the number of interneurons immunoreactive for ChAT and VIP in the EC had returned to normal values, and persisted for as long as 6 months after the lesion. By contrast, ChAT-ir neurons in the HDB were permanently lost. Our results suggest that the transient down-regulation of the cholinergic phenotype in entorhinal cortex interneurons could be a manifestation of activity-dependent plasticity, and that the loss of cholinergic innervation from the basal forebrain could be responsible for these effects through an imbalance of inputs. We hypothesize that the recovery of the phenotypic expression of entorhinal interneurons could be due to a recovery in their innervation, perhaps from sprouting axons in the same fields, belonging to surviving cholinergic neurons in the basal forebrain.
本实验旨在确定基底前脑胆碱能系统损伤对大鼠内嗅皮质（EC）中胆碱能中间神经元的影响。向布罗卡水平对角带核（HDB）单侧注入192 IgG-皂草素可使同侧胆碱乙酰转移酶免疫反应性（ChAT-ir）神经元数量减少54%。损伤后2至4周，同侧EC出现中度但显著的ChAT-ir纤维和中间神经元丢失。相邻切片显示血管活性肠肽（VIP）免疫反应性平行降低。扣带回皮质的细胞计数未受影响，表明这种效应确实特异性地作用于HDB神经元的主要靶区。鹅膏蕈氨酸损伤也导致同侧HDB中胆碱能神经元数量显著减少36%，以及EC中ChAT终末消失，而EC中ChAT-ir神经元数量未变。由于鹅膏蕈氨酸影响所有细胞而非仅胆碱能细胞，我们的结果表明，192 IgG-皂草素处理后HDB中胆碱能神经元的特异性变性可能对其靶标产生跨突触效应。直接向EC注射192 IgG-皂草素也损伤了来自HDB的胆碱能投射，但对内在神经元群体无影响。免疫损伤8周后，EC中对ChAT和VIP免疫反应的中间神经元数量已恢复到正常值，并在损伤后长达6个月持续存在。相比之下，HDB中的ChAT-ir神经元永久丢失。我们的结果表明，内嗅皮质中间神经元胆碱能表型的短暂下调可能是活性依赖可塑性的一种表现，并且基底前脑胆碱能神经支配的丧失可能通过输入失衡导致这些效应。我们推测，内嗅中间神经元表型表达的恢复可能是由于其神经支配的恢复，可能来自同一区域发芽的轴突，这些轴突属于基底前脑存活的胆碱能神经元。
