Hsieh C Y, Cruikshank S J, Metherate R
Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-4550, USA.
Brain Res. 2000 Oct 13;880(1-2):51-64. doi: 10.1016/s0006-8993(00)02766-9.
To investigate synaptic mechanisms underlying information processing in auditory cortex, we examined cholinergic modulation of synaptic transmission in a novel slice preparation containing thalamocortical and intracortical inputs to mouse auditory cortex. Extracellular and intracellular recordings were made in cortical layer IV while alternately stimulating thalamocortical afferents (via medial geniculate or downstream subcortical stimulation) and intracortical afferents. Either subcortical or intracortical stimulation elicited a fast, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive, monosynaptic EPSP followed by long-duration, polysynaptic activity. The cholinergic agonist carbachol suppressed each of the synaptic potentials to different degrees. At low concentrations (5 microM) carbachol strongly reduced (>60%) the polysynaptic slow potentials for both pathways but did not affect the monosynaptic fast potentials. At higher doses (10-50 microM), carbachol also reduced the fast potentials, but reduced the intracortically-elicited fast potential significantly more than the thalamocortically-elicited fast potential, which at times was actually enhanced. Atropine (0.5 microM) blocked the effects of carbachol, indicating muscarinic receptor involvement. We conclude that muscarinic modulation can strongly suppress intracortical synaptic activity while exerting less suppression, or actually enhancing, thalamocortical inputs. Such differential actions imply that auditory information processing may favor sensory information relayed through the thalamus over ongoing cortical activity during periods of increased acetylcholine (ACh) release.
为了研究听觉皮层信息处理背后的突触机制，我们在一种新型脑片标本中检测了突触传递的胆碱能调制，该标本包含小鼠听觉皮层的丘脑皮质和皮质内输入。在皮质第IV层进行细胞外和细胞内记录，同时交替刺激丘脑皮质传入纤维（通过内侧膝状体或下游皮质下刺激）和皮质内传入纤维。皮质下或皮质内刺激均可引发快速的、对6-氰基-7-硝基喹喔啉-2,3-二酮（CNQX）敏感的单突触兴奋性突触后电位（EPSP），随后是长时间的多突触活动。胆碱能激动剂卡巴胆碱对每种突触电位有不同程度的抑制作用。在低浓度（5微摩尔）时，卡巴胆碱强烈降低（>60%）两条通路的多突触慢电位，但不影响单突触快电位。在较高剂量（10-50微摩尔）时，卡巴胆碱也降低快电位，但对皮质内引发的快电位的降低幅度明显大于丘脑皮质引发的快电位，有时丘脑皮质引发的快电位实际上还会增强。阿托品（0.5微摩尔）可阻断卡巴胆碱的作用，表明涉及毒蕈碱受体。我们得出结论，毒蕈碱调制可强烈抑制皮质内突触活动，而对丘脑皮质输入的抑制作用较小，甚至实际上会增强。这种差异作用意味着在乙酰胆碱（ACh）释放增加的时期，听觉信息处理可能更有利于通过丘脑传递的感觉信息而非正在进行的皮质活动。
