Björklund A, Nilsson O G, Kalén P
Department of Medical Cell Research, University of Lund, Sweden.
Prog Brain Res. 1990;83:411-26. doi: 10.1016/s0079-6123(08)61265-0.
Subcortical deafferentation of the hippocampal formation is known to induce profound behavioural deficits. Transplants of fetal septal or brainstem tissue are capable of restoring some aspects of normal physiological and behavioural function in subcortically deafferented (i.e. fimbria-fornix or septal lesioned) rats. Such grafts have been shown to re-establish extensive new afferent inputs to the denervated hippocampal formation. As shown for grafted cholinergic and noradrenergic neurons, the ingrowing axons form laminar innervation patterns which closely mimic those of the normal cholinergic and noradrenergic innervations. The ingrowth appears to be very precisely regulated by the denervated target: each neuron type produces distinctly different innervation patterns; the growth is inhibited by the presence of an intact innervation of the same type; and it is stimulated by additional denervating lesions. Both ultrastructually and electrophysiologically the graft-derived fibres have been seen to form extensive functional synaptic contacts. Biochemically, cholinergic septal grafts and noradrenergic locus coeruleus grafts restore transmitter synthesis and turnover in the reinnervated hippocampus. Intracerebral microdialysis has revealed that acetylcholine and noradrenaline release is restored to normal or supranormal levels in the graft-reinnervated hippocampus, and that the grafted neurons can be activated in a normal way from the host through behavioural activation induced by sensory stimulation or electrical stimulation of the lateral habenula. These results indicate that the grafted monoaminergic neurons can restore tonic regulatory neurotransmission at previously denervated synaptic sites even when they are implanted into the ectopic brain sites. Such functional reafferentation may be sufficient for at least partial restoration of function in the subcortically deafferented hippocampus.
已知海马结构的皮质下传入神经切断会导致严重的行为缺陷。胎儿隔区或脑干组织移植能够恢复皮质下传入神经切断（即穹窿海马伞或隔区损伤）大鼠正常生理和行为功能的某些方面。已表明此类移植可重新建立广泛的新传入神经输入至去神经支配的海马结构。如移植的胆碱能和去甲肾上腺素能神经元所示，向内生长的轴突形成层状支配模式，与正常胆碱能和去甲肾上腺素能支配模式极为相似。这种向内生长似乎受到去神经支配靶点的精确调控：每种神经元类型产生明显不同的支配模式；同类型完整支配的存在会抑制生长；额外的去神经损伤则会刺激生长。从超微结构和电生理学角度均已观察到移植来源的纤维形成广泛的功能性突触联系。在生物化学方面，胆碱能隔区移植和去甲肾上腺素能蓝斑移植可恢复再支配海马中的递质合成及更新。脑内微透析显示，移植再支配的海马中乙酰胆碱和去甲肾上腺素释放恢复至正常或超正常水平，并且移植的神经元可通过感觉刺激或外侧缰核电刺激诱导的行为激活以正常方式从宿主获得激活。这些结果表明，即使将移植的单胺能神经元植入异位脑区，它们也能在先前去神经支配的突触部位恢复紧张性调节性神经传递。这种功能性再传入神经可能足以至少部分恢复皮质下传入神经切断的海马中的功能。
