Department of Neurobiology, Northwestern University, Evanston, United States.
Elife. 2020 Mar 24;9:e54302. doi: 10.7554/eLife.54302.
Innate defensive behaviors, such as freezing, are adaptive for avoiding predation. Freezing-related midbrain regions project to the cerebellum, which is known to regulate rapid sensorimotor integration, raising the question of cerebellar contributions to freezing. Here, we find that neurons of the mouse medial (fastigial) cerebellar nuclei (mCbN), which fire spontaneously with wide dynamic ranges, send glutamatergic projections to the ventrolateral periaqueductal gray (vlPAG), which contains diverse cell types. In freely moving mice, optogenetically stimulating glutamatergic vlPAG neurons that express Chx10 reliably induces freezing. In vlPAG slices, mCbN terminals excite ~20% of neurons positive for Chx10 or GAD2 and ~70% of dopaminergic TH-positive neurons. Stimulating either mCbN afferents or TH neurons augments IPSCs and suppresses EPSCs in Chx10 neurons by activating postsynaptic D receptors. The results suggest that mCbN activity regulates dopaminergic modulation of the vlPAG, favoring inhibition of Chx10 neurons. Suppression of cerebellar output may therefore facilitate freezing.
先天防御行为，如冻结，是适应于避免被捕食的。与冻结相关的中脑区域投射到小脑，小脑已知调节快速感觉运动整合，这就提出了小脑对冻结的贡献的问题。在这里，我们发现，具有广泛动态范围的自发放电的小鼠内侧（fastigial）小脑核（mCbN）神经元向包含多种细胞类型的腹外侧导水管周围灰质（vlPAG）投射谷氨酸能投射。在自由活动的小鼠中，光遗传学刺激表达 Chx10 的谷氨酸能 vlPAG 神经元可靠地诱导冻结。在 vlPAG 切片中，mCbN 末梢兴奋 Chx10 或 GAD2 阳性的神经元约 20%，多巴胺能 TH 阳性神经元约 70%。刺激 mCbN 传入或 TH 神经元通过激活突触后 D 受体增加 Chx10 神经元中的 IPSCs 并抑制 EPSCs。结果表明，mCbN 活性调节 vlPAG 中的多巴胺能调制，有利于抑制 Chx10 神经元。因此，小脑输出的抑制可能有助于冻结。
