Zheng F, Khanna S
Department of Physiology MD9, The National University of Singapore, 2 Medical Drive, 117597, Singapore, Singapore.
Neuroscience. 2001;103(4):985-98. doi: 10.1016/s0306-4522(01)00006-9.
Using extracellular recording techniques in urethane- (1g/kg, i.p.) anaesthetized rats, we investigated the influence exercised by medial septal cholinergic neurons on dorsal hippocampus field CA1 neural responses to a hind paw injection of formalin (5%, 0.05 ml, s.c.). Cholinergic neurons of the medial septal region were destroyed by local microinjection of the immunotoxin 192 IgG-saporin. Compared to control vehicle microinjected animals, immunotoxin-treatment attenuated the amplitude, but not frequency, of CA1 theta induced by intraseptal injection of carbachol. This suggested a selective destruction of medial septal cholinergic neurons by the immunotoxin. Such destruction also abolished; (i) intraseptal carbachol-induced suppression of CA1 population spike, and (ii) stimulation-intensity dependent increase in amplitude, but not frequency, of theta evoked on electrical stimulation in the region of oral part of pontine reticular nucleus. Further, in comparison to vehicle-treated animals, selective cholinergic destruction attenuated formalin-induced; (i) theta activation, (ii) suppression of CA1 pyramidal cell population spike and dendritic field excitatory post-synaptic potential, (iii) inhibition of complex spike cell extracellular activity, and (iv) excitation and theta-rhythmicity of local putative GABAergic interneurons. However, pretreatment with the immunotoxin did not alter the strength and proportion of complex spike cells excited following injection of formalin. From these findings we suggest that medial septal cholinergic neurons mediate, at least partly, the amplitude of theta and pyramidal cell suppression via an inhibitory network involving CA1 interneurons. The data also indicates that during formalin theta, the cholinergic-mediated inhibitory processing does not modulate the strength and selectivity of complex spike cell excitation. This points to formalin-induced, non-overlapping inhibitory and excitatory processes that might have different functional relevance.
利用细胞外记录技术，在腹腔注射氨基甲酸乙酯（1g/kg）麻醉的大鼠中，我们研究了内侧隔区胆碱能神经元对后爪注射福尔马林（5%，0.05ml，皮下注射）时海马背侧CA1区神经反应的影响。通过局部微量注射免疫毒素192 IgG-皂草素破坏内侧隔区的胆碱能神经元。与注射对照载体的动物相比，免疫毒素处理减弱了由隔区内注射卡巴胆碱诱导的CA1区θ波的振幅，但不影响其频率。这表明免疫毒素选择性地破坏了内侧隔区的胆碱能神经元。这种破坏还消除了：（i）隔区内卡巴胆碱诱导的CA1区群体峰电位的抑制，以及（ii）脑桥网状核口部区域电刺激诱发的θ波振幅随刺激强度的增加，但不影响其频率。此外，与载体处理的动物相比，选择性胆碱能破坏减弱了福尔马林诱导的：（i）θ波激活，（ii）CA1锥体细胞群体峰电位和树突野兴奋性突触后电位的抑制，（iii）复合峰电位细胞细胞外活动的抑制，以及（iv）局部假定的GABA能中间神经元的兴奋和θ节律。然而，用免疫毒素预处理并没有改变注射福尔马林后兴奋的复合峰电位细胞的强度和比例。从这些发现中我们认为，内侧隔区胆碱能神经元至少部分地通过涉及CA1中间神经元的抑制性网络介导θ波的振幅和锥体细胞的抑制。数据还表明，在福尔马林诱发的θ波期间，胆碱能介导的抑制性处理不会调节复合峰电位细胞兴奋的强度和选择性。这表明福尔马林诱导了不重叠的抑制性和兴奋性过程，它们可能具有不同的功能相关性。
