A two-layer biophysical model of cholinergic neuromodulation in olfactory bulb.
A two-layer biophysical model of cholinergic neuromodulation in olfactory bulb.
复制标题
DOI：
10.1523/jneurosci.2831-12.2013
复制
发表时间：
2013-02-13
期刊：
影响因子：
--
通讯作者：
Cleland TA
中科院分区：
文献类型：
--
作者：
Li G;Cleland TA
来自基底前脑的胆碱能输入调节多种嗅球（OB）功能，包括气味识别，知觉学习和短期记忆。先前的研究表明，烟碱能受体的激活使二尖瓣细胞的化学感受野变得尖锐，这可能是通过小球粒内回路实现的。尽管毒蕈碱受体与嗅觉学习和海马和皮质同步振荡动力学的调节有关，但对毒蕈碱能的激活知之甚少。为了了解OB中胆碱能神经调节的机制，我们建立了OB神经元网络的生物物理模型，包括肾小球层和外丛状层（EPL）的计算，并结合烟碱和毒蕈碱的神经调节作用。我们的模拟显示，即使在没有EPL回路的情况下，肾小球回路中的尼古丁激活如何使二尖瓣细胞化学感受野变得尖锐，但不促进内在振荡或尖峰同步。相比之下，毒毒碱受体激活通过增强颗粒细胞的兴奋性和EPL内的横向抑制相互作用，增加二尖瓣细胞尖峰同步和场振荡功率，但对二尖瓣细胞放电率几乎没有影响，因此在速率度量下不会增强嗅觉表征。这些结果与EPL相互作用调节二尖瓣细胞动作电位的时间而不是存在的理论是一致的，并根据基于尖峰时间的度量进行计算。这个通用模型表明，烟碱受体和毒蕈碱受体在嗅球中的作用既不同又互补，共同调节提升胆碱能输入对嗅球转化的影响。
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 has little effect on mitral cell firing rates and hence will 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.