Prakash Neal, Cohen-Cory Susana, Penschuck Silke, Frostig Ron D
Departments of Neurobiology and Behavior, University of California, Irvine, California 92697-4550, USA.
J Neurophysiol. 2004 Jan;91(1):424-37. doi: 10.1152/jn.00489.2003. Epub 2003 Sep 24.
We have previously reported that topical application of nerve growth factor (NGF) to the barrel cortex of an adult rat rapidly augmented a whisker functional representation (WFR) by increasing its area and height within minutes after NGF application. In addition, we found that TrkA, the high-affinity NGF receptor, was only found on fibers projecting into the barrel cortex. Here we use a combination of techniques including chronic intrinsic signal optical imaging, neuronal fiber tracking and immunohistological techniques, to test the hypothesis that NGF-induced rapid cortical plasticity is mediated by the cortical projections of the basal forebrain cholinergic system (BFCS). Our studies localize the source of the cells in the BFCS that project to a single WFR and also demonstrate that TrkA-immunoreactive fibers in the cortex are also cholinergic and likely arise from the BFCS. In addition, by selectively lesioning the BFCS cortical fibers with the immunotoxin 192 IgG-saporin, we show that NGF-induced WFR-cortical plasticity is eliminated. These results, taken together with our previously reported imaging results that demonstrated that agonists of the cholinergic system (particularly nicotine) showed transient NGF-like augmentations of a WFR, implicate the BFCS cortical projections as necessary for NGF's rapid plasticity in the adult rat somatosensory cortex.
我们之前报道过,将神经生长因子(NGF)局部应用于成年大鼠的桶状皮质,在应用NGF后的几分钟内,通过增加其面积和高度,能迅速增强触须功能表征(WFR)。此外,我们发现,高亲和力NGF受体TrkA仅在投射到桶状皮质的纤维上被发现。在此,我们运用包括慢性内在信号光学成像、神经元纤维追踪和免疫组织学技术在内的多种技术组合,来检验如下假设:NGF诱导的快速皮质可塑性是由基底前脑胆碱能系统(BFCS)的皮质投射介导的。我们的研究确定了BFCS中投射到单个WFR的细胞来源,还证明了皮质中TrkA免疫反应性纤维也是胆碱能的,并且可能起源于BFCS。此外,通过用免疫毒素192 IgG-皂草素选择性损伤BFCS皮质纤维,我们发现NGF诱导的WFR-皮质可塑性被消除了。这些结果,连同我们之前报道的成像结果(即胆碱能系统的激动剂(特别是尼古丁)显示出WFR的短暂NGF样增强),表明BFCS皮质投射是成年大鼠体感皮质中NGF快速可塑性所必需的。