Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System
Dynamic Impairment of Olfactory Behavior and Signaling Mediated by an Olfactory Corticofugal System
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DOI：
10.1523/jneurosci.2667-19.2020
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发表时间：
2020-08
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影响因子：
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通讯作者：
Renata Medinaceli Quintela;Jennifer Bauer;Lutz Wallhorn;K. Le;Daniela Brunert;Markus Rothermel
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作者：
Renata Medinaceli Quintela;Jennifer Bauer;Lutz Wallhorn;K. Le;Daniela Brunert;Markus Rothermel
嗅觉信息的处理是由皮质区域的离心式投射调节的，然而在大多数情况下，它们的行为相关性和潜在的神经机制仍然不清楚。前嗅核(AON)是嗅皮层的一部分，它与多个上下游脑中心的广泛联系使其在调节嗅觉系统早期感觉信息方面处于有利地位。在这里，我们表明，觉醒的雄性和雌性小鼠的Aon神经元的光遗传激活并不被认为是气味等同的线索。然而，气味呈现过程中的AON激活可靠地抑制了行为气味反应。这种Aon介导的效应在不同气味和浓度下都是快速和恒定的。同样，向嗅球(OB)的谷氨酸能AON投射的激活，一过性地抑制将嗅觉输入传递到大脑皮层的二尖瓣/簇状细胞(MTCs)的兴奋性。单单位MTC记录显示，OB区谷氨酸能Aon终末的光遗传激活可暂时降低感觉诱发的MTC峰，而与感觉反应的强度或极性无关。在清醒小鼠的记录中，证实了光遗传刺激期间MTC放电的减少。这些发现表明，谷氨酸能AON投射到OB区，通过抑制OB区的输出神经元，从而动态地将感觉传递到大脑皮层，从而阻碍早期的嗅觉信号传递。意义前嗅核(AON)作为嗅觉信息处理区，向多个大脑中枢发送广泛的投射，但其激活的行为后果很少被研究。使用行为测试和光基因操作相结合，我们表明，与之前提出的相反，Aon似乎没有形成气味感知，而是抑制了不同气味物质和浓度的行为气味反应。此外，本研究表明，在麻醉和清醒的小鼠中，AON的激活都抑制了嗅球输出神经元，这表明了一种潜在的机制，通过这种机制，嗅觉皮质可以主动和动态地将感觉传递到更高的大脑中心。
Processing of olfactory information is modulated by centrifugal projections from cortical areas, yet their behavioral relevance and underlying neural mechanisms remain unclear in most cases. The anterior olfactory nucleus (AON) is part of the olfactory cortex, and its extensive connections to multiple upstream and downstream brain centers place it in a prime position to modulate early sensory information in the olfactory system. Here, we show that optogenetic activation of AON neurons in awake male and female mice was not perceived as an odorant equivalent cue. However, AON activation during odorant presentation reliably suppressed behavioral odor responses. This AON-mediated effect was fast and constant across odors and concentrations. Likewise, activation of glutamatergic AON projections to the olfactory bulb (OB) transiently inhibited the excitability of mitral/tufted cells (MTCs) that relay olfactory input to the cortex. Single-unit MTC recordings revealed that optogenetic activation of glutamatergic AON terminals in the OB transiently decreased sensory-evoked MTC spiking, regardless of the strength or polarity of the sensory response. The reduction in MTC firing during optogenetic stimulation was confirmed in recordings in awake mice. These findings suggest that glutamatergic AON projections to the OB impede early olfactory signaling by inhibiting OB output neurons, thereby dynamically gating sensory throughput to the cortex. SIGNIFICANCE STATEMENT The anterior olfactory nucleus (AON) as an olfactory information processing area sends extensive projections to multiple brain centers, but the behavioral consequences of its activation have been scarcely investigated. Using behavioral tests in combination with optogenetic manipulation, we show that, in contrast to what has been suggested previously, the AON does not seem to form odor percepts but instead suppresses behavioral odor responses across odorants and concentrations. Furthermore, this study shows that AON activation inhibits olfactory bulb output neurons in both anesthetized as well as awake mice, pointing to a potential mechanism by which the olfactory cortex can actively and dynamically gate sensory throughput to higher brain centers.