Salman Farzaan, Jonaitis Julius, Ralston Jacob D, Cook Oliver M, Bennett Marryn M, Sizemore Tyler R, Ramachandra Keshav L, Coates Kaylynn E, Fox Jessica L, Dacks Andrew M
Department of Biology, West Virginia University, Morgantown, United States of America.
Department of Neurobiology, Harvard Medical School, Boston, United States of America.
bioRxiv. 2025 Aug 22:2025.08.19.671125. doi: 10.1101/2025.08.19.671125.
Inhibitory local interneurons (LNs) play an essential role in sensory processing by refining stimulus representations via a diverse collection of mechanisms. The morphological and physiological traits of individual LN types, as well as their connectivity within sensory networks, enable each LN type to support different computations such as lateral inhibition or gain control and are therefore ideal targets for modulatory neurons to have widespread impacts on network activity. In this study, we combined detailed connectivity analyses, serotonin receptor expression, neurophysiology, and computational modeling to demonstrate the functional impact of serotonin on a constrained LN network in the olfactory system of . This subnetwork is composed of three LN types and we describe each of their distinctive morphology, connectivity, biophysical properties and odor response properties. We demonstrate that each LN type expresses different combinations of serotonin receptors and that serotonin differentially impacts the excitability of each LN type. Finally, by applying these serotonin induced changes in excitability to a computational model that simulates the impact of inhibition exerted by each LN-type, we predict a role for serotonin in adjusting the dynamic range of antennal lobe output neurons and in noise reduction in odor representations. Thus, a single modulatory system can differentially impact LN types that subserve distinct roles within the olfactory system.
抑制性局部中间神经元(LNs)在感觉处理中起着至关重要的作用,它们通过多种机制优化刺激表征。单个LN类型的形态和生理特征,以及它们在感觉网络中的连接性,使每种LN类型能够支持不同的计算,如侧向抑制或增益控制,因此是调节性神经元对网络活动产生广泛影响的理想靶点。在本研究中,我们结合了详细的连接性分析、5-羟色胺受体表达、神经生理学和计算建模,以证明5-羟色胺对果蝇嗅觉系统中一个受限的LN网络的功能影响。这个子网由三种LN类型组成,我们描述了它们各自独特的形态、连接性、生物物理特性和气味反应特性。我们证明每种LN类型表达不同组合的5-羟色胺受体,并且5-羟色胺对每种LN类型的兴奋性有不同的影响。最后,通过将这些由5-羟色胺诱导的兴奋性变化应用于一个模拟每种LN类型施加的抑制作用影响的计算模型,我们预测5-羟色胺在调节触角叶输出神经元的动态范围和减少气味表征中的噪声方面发挥作用。因此,一个单一的调节系统可以对在嗅觉系统中发挥不同作用的LN类型产生不同的影响。