Spatially anisotropic and isotropic lateral inhibition: Convergent circuit designs in the insect antennal lobe and vertebrate olfactory bulb

抑制性神经元是神经系统的重要组成部分，平衡和调节兴奋性神经子网络的输出。在动物王国的嗅觉系统中，抑制作用尤其占主导地位。高度复杂和密集的抑制回路控制感觉神经元输入的影响。然而更引人注目的是，抑制神经元是彼此缺乏直接突触接触的二级主神经元之间相互作用的主要介质。这些通路被认为以状态依赖的方式调节嗅觉灵敏度，提供增益控制，同步主神经元集合的尖峰活动，并通过它们的响应模式的去相关来增强相似气味的表征的对比度。昆虫和脊椎动物的底层网络解剖结构极其相似--这是趋同进化的一个典型例子。在这里，我们的目标是进一步澄清细胞相关的早期嗅觉过程中定义的抑制性相互作用跨门。更具体地说，我们将调查的细胞基础和功能的影响，在苍蝇触角叶和大鼠嗅球，即经常性抑制和各向同性和各向异性的侧抑制，后者允许直接相互作用的个别肾小球通道，甚至可能是硬连线的抑制形式。除了SPP资助期的第一阶段，重点是跨门的各向异性抑制，并且由于大流行而部分延迟，我们现在计划还确定果蝇中复发性抑制和各向同性侧抑制的解剖学相关性，最终将所提到的特定抑制相互作用分配给定义的中间神经元类型。接下来，我们将在实验中测试这些分配及其功能影响，这些实验涉及在先天和习得的气味引导行为期间相应的中间神经元亚型的靶向沉默。与此同时，我们计划将这些和以前的研究结果整合到谱系特异性网络模型中，这些模型基于来自最近超微结构数据和我们自己和他人工作的功能数据的现实神经解剖学参数。最终，我们的目标是使用这些模型来开发一个新的通用网络模型的收敛嗅觉系统，与其他成员的优先程序与计算和电路专业知识的紧密合作。

Inhibitory neurons are an essential component of nervous systems, balancing and modulating the output from excitatory neural subnetworks. Across olfactory systems in the animal kingdom, inhibition is particularly dominant. Highly complex and dense inhibitory circuits control the impact of sensory neuron input. Yet more strikingly, inhibitory neurons are the main mediators of interactions between second order principal neurons that lack direct synaptic contacts with each other. These pathways are thought to regulate olfactory sensitivity in a state-dependent manner, provide gain control, synchronize the spiking activity of principal neuron ensembles, and enhance the contrast of representations of similar odorants via decorrelation of their response patterns. The architecture of the underlying network anatomy is astonishingly similar across insects and vertebrates - a prime example of convergent evolution. Here we aim to further clarify the cellular correlates of defined inhibitory interactions within early olfactory processing across phylae. More specifically, we will investigate the cellular basis and functional impact of dominant forms of inhibition within the fly antennal lobe and the rat olfactory bulb, namely recurrent inhibition and isotropic and anisotropic lateral inhibition, the latter allowing for directed interactions between individual glomerular channels that might be even hard-wired. Beyond the first phase of the SPP funding period, that was focussed on anisotropic inhibition across phylae and in partly delayed due to the pandemic, we now plan to also identify the anatomical correlates of recurrent inhibition and isotropic lateral inhibition in the fly, to ultimately assign the mentioned specific inhibitory interactions to defined interneuron types. Next, we will test these assignments and their functional impact in experiments that involve targeted silencing of the respective interneuron subtypes during innate and learned odor-guided behavior. In parallel we plan to integrate the results of these and previous investigations into lineage-specific network models that are based on realistic neuroanatomical parameters derived from recent ultrastructural data and functional data from our own and others work. Ultimately, we aim to use these models to develop a new generic network model of the convergent olfactory system, in tight collaboration with other members of the priority program with computational and circuits expertise.