Rosenblad C, Nilsson O G
Department of Medical Cell Research, University of Lund, Sweden.
Neuroscience. 1993 Jul;55(2):353-62. doi: 10.1016/0306-4522(93)90504-9.
Acetylcholine release in the frontal cortex of awake rats after acute or chronic lesions of the nucleus basalis magnocellularis and grafting of cholinergic-rich basal forebrain tissue was studied by in vivo microdialysis. Three to four weeks and five months after a unilateral quisqualic acid lesion of the nucleus basalis, and five months after lesion and cortical implantation of a basal forebrain cell suspension, acetylcholine release was characterized during a range of pharmacological and behavioural manipulations. Neostigmine (5 microM) was added to the perfusion fluid in order to inhibit the degradation of acetylcholine. The extracellular levels of acetylcholine in normal animals increased three- to four-fold when KCl (100 mM) was added to the perfusion medium and was reduced by 80% after addition of tetrodotoxin (1 microM). The nucleus basalis lesion resulted in a 60% reduction in baseline acetylcholine levels compared to normal and the response to KCl-evoked depolarization was significantly reduced. There were no differences between the acute and chronic lesion groups during any of the manipulations performed. Rats with grafts showed baseline levels of acetylcholine about 70% higher than normal, and responded to both KCl (two-fold increased acetylcholine release) and tetrodotoxin (85% reduced levels). All groups showed lower acetylcholine levels during halothane anaesthesia (on average 70-85% reduction). Sensory stimulation by handling resulted in a two-fold increase in acetylcholine release in normal animals, whereas the absolute responses in the lesioned controls were significantly weaker. Rats with grafts increased their acetylcholine release after handling to an extent not different to normal or lesioned controls. Immobilization stress induced an almost two-fold increase in cortical acetylcholine levels in normal rats, whereas the effect in the lesion-only groups was very weak. The grafts responded to the immobilization with an enhanced acetylcholine overflow that was significantly higher than in lesioned controls. The results showed that the reduction in frontocortical acetylcholine release induced by excitotoxic lesions of the nucleus basalis did not recover spontaneously over several months. Intracortical cholinergic-rich grafts obtained from the fetal basal forebrain provided a source of acetylcholine release with firing-dependent properties which could be modulated by behaviourally stressful stimuli. The ability of the grafts to respond to behavioural manipulation strongly suggests that the host brain can functionally influence graft neuronal activity during ongoing behaviour. Host control of graft activity may play a role in the recovery of the lesion-induced deficits seen with these types of grafts.
通过体内微透析研究了在基底大细胞核急性或慢性损伤以及富含胆碱能的基底前脑组织移植后清醒大鼠额叶皮质中的乙酰胆碱释放情况。在基底核单侧喹啉酸损伤后的三到四周和五个月，以及损伤并植入基底前脑细胞悬液后的五个月，在一系列药理和行为操作过程中对乙酰胆碱释放进行了表征。向灌注液中添加新斯的明（5微摩尔）以抑制乙酰胆碱的降解。当向灌注培养基中添加氯化钾（100毫摩尔）时，正常动物细胞外乙酰胆碱水平增加三到四倍，添加河豚毒素（1微摩尔）后降低80%。与正常情况相比，基底核损伤导致基线乙酰胆碱水平降低60%，对氯化钾诱发的去极化反应明显减弱。在进行的任何操作过程中，急性和慢性损伤组之间均无差异。移植大鼠的乙酰胆碱基线水平比正常水平高约70%，对氯化钾（乙酰胆碱释放增加两倍）和河豚毒素（水平降低85%）均有反应。所有组在氟烷麻醉期间乙酰胆碱水平均较低（平均降低70 - 85%）。通过处理进行感觉刺激导致正常动物乙酰胆碱释放增加两倍，而损伤对照组的绝对反应明显较弱。移植大鼠在处理后乙酰胆碱释放增加，增加程度与正常或损伤对照组无差异。固定应激在正常大鼠中诱导皮质乙酰胆碱水平几乎增加两倍，而仅损伤组的效应非常微弱。移植对固定应激的反应是乙酰胆碱溢出增强，明显高于损伤对照组。结果表明，基底核兴奋性毒性损伤引起的额叶皮质乙酰胆碱释放减少在几个月内不会自发恢复。从胎儿基底前脑获得的皮质内富含胆碱能的移植物提供了一种具有放电依赖性特性的乙酰胆碱释放源，其可受到行为应激刺激的调节。移植物对行为操作作出反应的能力强烈表明，宿主大脑在持续行为过程中可在功能上影响移植物神经元活动。宿主对移植物活动的控制可能在这些类型移植物所见的损伤诱导缺陷的恢复中起作用。
