Saar Drorit, Dadon Moran, Leibovich Marcela, Sharabani Hagar, Grossman Yoram, Heldman Eliahu
Department of Physiology, Faculty for Health Sciences and Zlotowski Center for Neuroscience, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Learn Mem. 2007 Mar 9;14(3):224-8. doi: 10.1101/lm.452307. Print 2007 Mar.
We combined pharmacological studies and electrophysiological recordings to investigate modifications in muscarinic acetylcholine (ACh) receptors (mAChR) in the rat olfactory (piriform) cortex, following odor-discrimination rule learning. Rats were trained to discriminate between positive and negative cues in pairs of odors, until they reached a phase of high capability to learn unfamiliar odors, using the same paradigm ("rule learning"). It has been reported that at 1-3 d after the acquisition of odor-discrimination rule learning, pyramidal neurons in the rat piriform cortex show enhanced excitability, due to a reduction in the spike-activated potassium current I(AHP), which is modulated by ACh. Further, ACh and its analog, carbachol (CCh), lost the ability to reduce the I(AHP) in neurons from trained rats. Here we show that the reduced sensitivity to CCh in the piriform cortex results from a decrease in the number of mAChRs, as well as a reduction in the affinity of the receptors to CCh. Also, it has been reported that 3-8 d after the acquisition of odor-discrimination rule learning, synaptic transmission in the piriform cortex is enhanced, and paired-pulse facilitation (PPF) in response to twin stimulations is reduced. Here, intracellular recordings from pyramidal neurons show that CCh increases PPF in the piriform cortex from odor-trained rats more than in control rats, suggesting enhanced effect of ACh in inhibiting presynaptic glutamate release after odor training.
我们结合药理学研究和电生理记录，以探究大鼠嗅觉（梨状）皮质中，在气味辨别规则学习后毒蕈碱型乙酰胆碱（ACh）受体（mAChR）的变化。大鼠接受训练以辨别成对气味中的正性和负性线索，直到它们使用相同范式（“规则学习”）达到能够高效学习陌生气味的阶段。据报道，在获得气味辨别规则学习后的1 - 3天，大鼠梨状皮质中的锥体神经元兴奋性增强，这是由于由ACh调节的锋电位激活钾电流I(AHP)减少所致。此外，ACh及其类似物卡巴胆碱（CCh）失去了降低训练大鼠神经元中I(AHP)的能力。在此我们表明，梨状皮质中对CCh敏感性降低是由于mAChRs数量减少以及受体对CCh的亲和力降低所致。另外，据报道，在获得气味辨别规则学习后的3 - 8天，梨状皮质中的突触传递增强，并且对双脉冲刺激的双脉冲易化（PPF）降低。在此，锥体神经元的细胞内记录显示，CCh在气味训练大鼠的梨状皮质中比在对照大鼠中更能增加PPF，这表明气味训练后ACh在抑制突触前谷氨酸释放方面的作用增强。
