Smith Richard S, Hu Ruilong, DeSouza Andre, Eberly Christian L, Krahe Krista, Chan Wilson, Araneda Ricardo C
Department of Biology, University of Maryland, College Park, Maryland 20742.
Department of Biology, University of Maryland, College Park, Maryland 20742
J Neurosci. 2015 Jul 29;35(30):10773-85. doi: 10.1523/JNEUROSCI.0099-15.2015.
Neuromodulation of olfactory circuits by acetylcholine (ACh) plays an important role in odor discrimination and learning. Early processing of chemosensory signals occurs in two functionally and anatomically distinct regions, the main and accessory olfactory bulbs (MOB and AOB), which receive extensive cholinergic input from the basal forebrain. Here, we explore the regulation of AOB and MOB circuits by ACh, and how cholinergic modulation influences olfactory-mediated behaviors in mice. Surprisingly, despite the presence of a conserved circuit, activation of muscarinic ACh receptors revealed marked differences in cholinergic modulation of output neurons: excitation in the AOB and inhibition in the MOB. Granule cells (GCs), the most abundant intrinsic neuron in the OB, also exhibited a complex muscarinic response. While GCs in the AOB were excited, MOB GCs exhibited a dual muscarinic action in the form of a hyperpolarization and an increase in excitability uncovered by cell depolarization. Furthermore, ACh influenced the input-output relationship of mitral cells in the AOB and MOB differently showing a net effect on gain in mitral cells of the MOB, but not in the AOB. Interestingly, despite the striking differences in neuromodulatory actions on output neurons, chemogenetic inhibition of cholinergic neurons produced similar perturbations in olfactory behaviors mediated by these two regions. Decreasing ACh in the OB disrupted the natural discrimination of molecularly related odors and the natural investigation of odors associated with social behaviors. Thus, the distinct neuromodulation by ACh in these circuits could underlie different solutions to the processing of general odors and semiochemicals, and the diverse olfactory behaviors they trigger.
State-dependent cholinergic modulation of brain circuits is critical for several high-level cognitive functions, including attention and memory. Here, we provide new evidence that cholinergic modulation differentially regulates two parallel circuits that process chemosensory information, the accessory and main olfactory bulb (AOB and MOB, respectively). These circuits consist of remarkably similar synaptic arrangement and neuronal types, yet cholinergic regulation produced strikingly opposing effects in output and intrinsic neurons. Despite these differences, the chemogenetic reduction of cholinergic activity in freely behaving animals disrupted odor discrimination of simple odors, and the investigation of social odors associated with behaviors signaled by the Vomeronasal system.
乙酰胆碱（ACh）对嗅觉回路的神经调节在气味辨别和学习中起重要作用。化学感觉信号的早期处理发生在两个功能和解剖结构不同的区域，即主嗅球和副嗅球（MOB和AOB），它们接收来自基底前脑的广泛胆碱能输入。在这里，我们探讨ACh对AOB和MOB回路的调节，以及胆碱能调制如何影响小鼠的嗅觉介导行为。令人惊讶的是，尽管存在保守回路，但毒蕈碱型ACh受体的激活揭示了输出神经元胆碱能调制的显著差异：AOB中为兴奋，MOB中为抑制。颗粒细胞（GCs）是嗅球中最丰富的内在神经元，也表现出复杂的毒蕈碱反应。虽然AOB中的GCs被兴奋，但MOB中的GCs表现出双重毒蕈碱作用，形式为超极化和细胞去极化后兴奋性增加。此外，ACh对AOB和MOB中二尖瓣细胞的输入-输出关系有不同影响，对MOB中二尖瓣细胞的增益有净效应，而对AOB中则没有。有趣的是，尽管对输出神经元的神经调节作用存在显著差异，但胆碱能神经元的化学遗传抑制在这两个区域介导的嗅觉行为中产生了类似的扰动。减少嗅球中的ACh会破坏对分子相关气味的自然辨别以及对与社会行为相关气味的自然探究。因此，ACh在这些回路中的独特神经调节可能是对一般气味和信息素处理以及它们触发的各种嗅觉行为的不同解决方案的基础。
大脑回路的状态依赖性胆碱能调制对包括注意力和记忆在内的几种高级认知功能至关重要。在这里，我们提供了新的证据，表明胆碱能调制分别对处理化学感觉信息的两个平行回路，即副嗅球和主嗅球（分别为AOB和MOB）进行差异调节。这些回路由非常相似的突触排列和神经元类型组成，但胆碱能调节在输出和内在神经元中产生了明显相反的作用。尽管存在这些差异，但在自由行为动物中胆碱能活性的化学遗传降低破坏了对简单气味的气味辨别以及对与犁鼻器系统发出信号的行为相关的社会气味的探究。
