Computational Physiology Laboratory, Department of Psychology, Cornell University, Ithaca, New York 14853, USA.
J Neurosci. 2013 Feb 13;33(7):3037-58. doi: 10.1523/JNEUROSCI.2831-12.2013.
Cholinergic inputs from the basal forebrain regulate multiple olfactory bulb (OB) functions, including odor discrimination, perceptual learning, and short-term memory. Previous studies have shown that nicotinic cholinergic receptor activation sharpens mitral cell chemoreceptive fields, likely via intraglomerular circuitry. Muscarinic cholinergic activation is less well understood, though muscarinic receptors are implicated in olfactory learning and in the regulation of synchronized oscillatory dynamics in hippocampus and cortex. To understand the mechanisms underlying cholinergic neuromodulation in OB, we developed a biophysical model of the OB neuronal network including both glomerular layer and external plexiform layer (EPL) computations and incorporating both nicotinic and muscarinic neuromodulatory effects. Our simulations show how nicotinic activation within glomerular circuits sharpens mitral cell chemoreceptive fields, even in the absence of EPL circuitry, but does not facilitate intrinsic oscillations or spike synchronization. In contrast, muscarinic receptor activation increases mitral cell spike synchronization and field oscillatory power by potentiating granule cell excitability and lateral inhibitory interactions within the EPL, but it has little effect on mitral cell firing rates and hence does not sharpen olfactory representations under a rate metric. These results are consistent with the theory that EPL interactions regulate the timing, rather than the existence, of mitral cell action potentials and perform their computations with respect to a spike timing-based metric. This general model suggests that the roles of nicotinic and muscarinic receptors in olfactory bulb are both distinct and complementary to one another, together regulating the effects of ascending cholinergic inputs on olfactory bulb transformations.
基底前脑的胆碱能输入调节多个嗅球 (OB) 功能，包括气味辨别、感知学习和短期记忆。先前的研究表明，烟碱型胆碱能受体的激活使僧帽细胞的化学感受野变锐，这可能是通过肾小球内的电路实现的。而对于毒蕈碱型胆碱能受体的激活则了解较少，尽管毒蕈碱型受体参与嗅觉学习以及海马体和皮层中同步振荡动力学的调节。为了了解 OB 中胆碱能神经调节的机制，我们开发了一个包括肾小球层和外丛状层 (EPL) 计算在内的 OB 神经元网络的生物物理模型，并整合了烟碱型和毒蕈碱型的神经调节效应。我们的模拟结果表明，在肾小球回路中激活烟碱型受体可以使僧帽细胞的化学感受野变锐，即使没有 EPL 回路也是如此，但不会促进固有振荡或尖峰同步。相比之下，毒蕈碱型受体的激活通过增强 EPL 中的颗粒细胞兴奋性和侧向抑制相互作用，增加了僧帽细胞的尖峰同步和场振荡功率，但对僧帽细胞的放电率影响不大，因此在基于尖峰时间的度量下，不会使嗅觉表示变锐。这些结果与 EPL 相互作用调节僧帽细胞动作电位的时间而不是存在的理论一致，并根据基于尖峰时间的度量来执行其计算。这个通用模型表明，烟碱型和毒蕈碱型受体在嗅球中的作用既独特又相互补充，共同调节上行胆碱能输入对嗅球转换的影响。
