Johnson F, Hohmann S E, DiStefano P S, Bottjer S W
Department of Psychology, Florida State University, Tallahassee, Florida 32306-1051, USA.
J Neurosci. 1997 Mar 15;17(6):2101-11. doi: 10.1523/JNEUROSCI.17-06-02101.1997.
Studies of the developing nervous system led to the general view that growth factors promote neuronal survival in a "retrograde" manner. For example, release of NGF from postsynaptic peripheral targets followed by uptake and retrograde transport by presynaptic neurons provided a widely accepted conceptual framework for the action of neurotrophins. In contrast, although presynaptic or "anterograde" influences on the survival of developing neurons have been recognized for some time, the mechanisms by which afferent input regulates the survival of postsynaptic cells have received considerably less attention. In the forebrain network for learned vocal behavior in zebra finches, lesions of a cortical region for song control, the lateral magnocellular nucleus of the anterior neostriatum (lMAN), remove presynaptic input to a motor-cortical song region, the robust nucleus of the archistriatum (RA), and cause massive RA neuron death in young birds that are entering the sensitive period for song learning. Here we report that lesions of lMAN followed by infusions of neurotrophins directly into RA completely suppress neuronal apoptosis in RA. Moreover, we show that lMAN neurons are able to transport neurotrophins in the anterograde direction to RA, that neurotrophin-like immunoreactivity is present in cells in lMAN and RA, and that neurotrophin receptor-like immunoreactivity is present in RA. Expression of neurotrophins in lMAN and RA suggests that lMAN presynaptic input could regulate RA neuron survival by synthesizing, transporting, and releasing neurotrophins anterogradely or by regulating the auto/paracrine release of neurotrophins within RA, or perhaps by both. These data provide the first in vivo demonstration that neurotrophins can prevent the death of deafferented cortical neurons, and they raise the possibility that nonretrograde signaling by neurotrophins may be a common means of promoting neuronal survival in the vertebrate telencephalon. Anterograde and auto/paracrine neurotrophin signaling, along with the more established view that neurotrophins regulate neuron survival via retrograde mechanisms, suggests multidirectional neurotrophin signaling in the vertebrate telencephalon.
对发育中的神经系统的研究得出了一个普遍观点，即生长因子以“逆行”方式促进神经元存活。例如，突触后外周靶标释放神经生长因子（NGF），随后由突触前神经元摄取并逆行运输，这为神经营养因子的作用提供了一个被广泛接受的概念框架。相比之下，尽管突触前或“顺行”对发育中神经元存活的影响已被认识一段时间了，但传入输入调节突触后细胞存活的机制却很少受到关注。在斑胸草雀用于学习发声行为的前脑网络中，一个用于控制鸣叫的皮质区域——新纹状体前部大细胞外侧核（lMAN）受损，会消除对运动皮质鸣叫区域——古纹状体粗核（RA）的突触前输入，并导致进入鸣叫学习敏感期的幼鸟中大量RA神经元死亡。在此，我们报告，lMAN受损后将神经营养因子直接注入RA可完全抑制RA中的神经元凋亡。此外，我们表明lMAN神经元能够将神经营养因子顺行运输至RA，lMAN和RA中的细胞存在神经营养因子样免疫反应性，且RA中存在神经营养因子受体样免疫反应性。lMAN和RA中神经营养因子的表达表明，lMAN的突触前输入可能通过顺行合成、运输和释放神经营养因子，或通过调节RA内神经营养因子的自分泌/旁分泌释放，或者可能通过两者来调节RA神经元的存活。这些数据首次在体内证明神经营养因子可防止去传入皮质神经元的死亡，并提出神经营养因子的非逆行信号传导可能是脊椎动物端脑中促进神经元存活的常见方式的可能性。顺行和自分泌/旁分泌神经营养因子信号传导，以及神经营养因子通过逆行机制调节神经元存活这一更为确定的观点，表明脊椎动物端脑中存在多向神经营养因子信号传导。
