Defensive responses to visually threatening stimuli represent an essential fear-related survival instinct, widely detected across species. The neural circuitry mediating visually triggered defensive responses has been delineated in the midbrain. However, the molecular mechanisms regulating the development and function of these circuits remain unresolved. Here, we show that midbrain-specific deletion of the transcription factor Brn3b causes a loss of neurons projecting to the lateral posterior nucleus of the thalamus. Brn3b deletion also down-regulates the expression of the neuropeptide tachykinin 2 (Tac2). Furthermore, Brn3b mutant mice display impaired defensive freezing responses to visual threat precipitated by social isolation. This behavioral phenotype could be ameliorated by overexpressing Tac2, suggesting that Tac2 acts downstream of Brn3b in regulating defensive responses to threat. Together, our experiments identify specific genetic components critical for the functional organization of midbrain fear-related visual circuits. Similar mechanisms may contribute to the development and function of additional long-range brain circuits underlying fear-associated behavior.

中文翻译：

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Brn3b 调节与恐惧相关的中脑回路的形成以及对视觉威胁的防御反应。

对视觉威胁刺激的防御反应代表了一种与恐惧相关的基本生存本能，在各个物种中广泛存在。介导视觉触发的防御反应的神经回路已在中脑中描绘出来。然而，调节这些回路的发育和功能的分子机制仍未解决。在这里，我们发现中脑特异性删除转录因子 Brn3b 会导致投射到丘脑外侧后核的神经元丢失。Brn3b 缺失还会下调神经肽速激肽 2 (Tac2) 的表达。此外，Brn3b 突变小鼠对社会孤立引起的视觉威胁表现出防御性冻结反应受损。这种行为表型可以通过过度表达 Tac2 得到改善，这表明 Tac2 在调节对威胁的防御反应方面发挥着 Brn3b 下游的作用。我们的实验共同确定了对中脑恐惧相关视觉回路的功能组织至关重要的特定遗传成分。类似的机制可能有助于恐惧相关行为背后的额外远程大脑回路的发育和功能。