Steckler T, Keith A B, Wiley R G, Sahgal A
MRC Neurochemical Pathology Unit, Newcastle General Hospital, Newcastle-upon-Tyne, U.K.
Neuroscience. 1995 May;66(1):101-14. doi: 10.1016/0306-4522(94)00603-3.
Two experiments examined the effects of cholinergic basal forebrain lesions by intraventricular and intrahippocampal infusions of the immunotoxin 192 IgG-saporin on recognition memory in an operant delayed-non-matching-to-position task in rats. Intraventricular infusions produced extensive reductions in cortical and hippocampal choline acetyltransferase activity in the first experiment. Behaviourally, a mixed delay-dependent/independent accuracy deficit and increased biased responding was observed post-lesioning. Thus, both mnemonic as well as non-mnemonic processes were affected by the lesion. This performance deficit was indistinguishable from the impairment induced by acute intraventricular injections of the choline uptake inhibitor hemicholinium-3, which suggests that cholinergic damage induced by 192 IgG-saporin disrupted performance. In the second experiment more discrete intrahippocampal 192 IgG-saporin lesions were made, which reduced hippocampal choline acetyltransferase activity about 57%, although this reduction was not as extensive as following intraventricular injections. Although intrahippocampal lesions also impaired non-matching accuracy, this effect failed to reach significance during most stages of the experiment. Scopolamine just failed to significantly impair (P = 0.053) performance in hippocampal lesioned rats more than in controls. The nicotinic antagonist mecamylamine did not affect the lesion-induced changes in performance. These results suggest that the cholinergic basal forebrain, including the septohippocampal system, is important for the mediation of recognition memory, and muscarinic receptor-mediated mechanisms may be of greater importance than alterations of nicotinic receptor-mediated processes in the septohippocampal system.
两项实验研究了通过脑室内和海马内注射免疫毒素192 IgG-皂草素造成胆碱能基底前脑损伤对大鼠操作性延迟位置不匹配任务中识别记忆的影响。在第一个实验中，脑室内注射导致皮质和海马胆碱乙酰转移酶活性大幅降低。行为学上，损伤后观察到混合的延迟依赖性/非依赖性准确性缺陷以及偏倚反应增加。因此，记忆过程和非记忆过程均受到损伤的影响。这种行为表现缺陷与急性脑室内注射胆碱摄取抑制剂半胱氨酸-3所诱导的损伤无法区分，这表明192 IgG-皂草素诱导的胆碱能损伤破坏了行为表现。在第二个实验中，制作了更离散的海马内192 IgG-皂草素损伤，海马胆碱乙酰转移酶活性降低了约57%，尽管这种降低不如脑室内注射后那么广泛。虽然海马内损伤也损害了不匹配准确性，但在实验的大多数阶段，这种影响未达到显著水平。东莨菪碱仅未能显著损害（P = 0.053）海马损伤大鼠的行为表现，其程度超过对照组。烟碱拮抗剂美加明不影响损伤诱导的行为表现变化。这些结果表明，包括隔海马系统在内的胆碱能基底前脑对于识别记忆的介导很重要，并且毒蕈碱受体介导的机制可能比隔海马系统中烟碱受体介导过程的改变更为重要。
