Carlson Kaitlin S, Whitney Meredith S, Gadziola Marie A, Deneris Evan S, Wesson Daniel W
Department of Neurosciences, Case Western Reserve University , Cleveland, OH, 44106.
eNeuro. 2016 Nov 17;3(5). doi: 10.1523/ENEURO.0257-16.2016. eCollection 2016 Sep-Oct.
The neurotransmitter serotonin (5-HT) is considered a powerful modulator of sensory system organization and function in a wide range of animals. The olfactory system is innervated by midbrain 5-HT neurons into both its primary and secondary odor-processing stages. Facilitated by this circuitry, 5-HT and its receptors modulate olfactory system function, including odor information input to the olfactory bulb. It is unknown, however, whether the olfactory system requires 5-HT for even its most basic behavioral functions. To address this question, we established a conditional genetic approach to specifically target adult brain (), encoding the rate-limiting enzyme in brain 5-HT synthesis, and nearly eliminate 5-HT from the mouse forebrain. Using this novel model, we investigated the behavior of 5-HT-depleted mice during performance in an olfactory go/no-go task. Surprisingly, the near elimination of 5-HT from the forebrain, including the olfactory bulbs, had no detectable effect on the ability of mice to perform the odor-based task. -targeted mice not only were able to learn the task, but also had levels of odor acuity similar to those of control mice when performing coarse odor discrimination. Both groups of mice spent similar amounts of time sampling odors during decision-making. Furthermore, odor reversal learning was identical between 5-HT-depleted and control mice. These results suggest that 5-HT neurotransmission is not necessary for the most essential aspects of olfaction, including odor learning, discrimination, and certain forms of cognitive flexibility.
神经递质5-羟色胺（5-HT）被认为是多种动物感觉系统组织和功能的强大调节因子。嗅觉系统由中脑5-HT神经元支配，涉及初级和次级气味处理阶段。在这种神经回路的作用下，5-HT及其受体调节嗅觉系统功能，包括输入嗅球的气味信息。然而，嗅觉系统是否甚至在其最基本的行为功能中都需要5-HT尚不清楚。为了解决这个问题，我们建立了一种条件性基因方法，专门针对成体大脑中编码大脑5-HT合成限速酶的（此处原文缺失具体基因名称），并几乎从小鼠前脑中消除5-HT。利用这个新模型，我们研究了5-HT缺失小鼠在嗅觉“去/不去”任务中的行为表现。令人惊讶的是，从前脑（包括嗅球）中几乎消除5-HT对小鼠执行基于气味任务的能力没有可检测到的影响。靶向（此处原文缺失具体靶向对象）的小鼠不仅能够学习任务，而且在进行粗略气味辨别时，其气味敏锐度水平与对照小鼠相似。两组小鼠在决策过程中花费相似的时间对气味进行采样。此外，5-HT缺失小鼠和对照小鼠在气味反转学习方面表现相同。这些结果表明，5-HT神经传递对于嗅觉的最基本方面，包括气味学习、辨别和某些形式的认知灵活性来说并非必要。
