Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Department of Biomedical Science, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Department of Physiology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Neuroscience Research Institute, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Cell Rep. 2023 Apr 25;42(4):112291. doi: 10.1016/j.celrep.2023.112291. Epub 2023 Mar 22.
Multiple brain regions are engaged in classical fear conditioning. Despite evidence for cerebellar involvement in fear conditioning, the mechanisms by which cerebellar outputs modulate fear learning and memory remain unclear. We identify a population of deep cerebellar nucleus (DCN) neurons with monosynaptic glutamatergic projections to the lateral parabrachial nucleus (lPBN) (DCN neurons) in mice. While optogenetic suppression of DCN neurons impairs auditory fear memory, activation of DCN neurons elicits freezing behavior only after auditory fear conditioning. Moreover, auditory fear conditioning potentiates DCN-lPBN synapses, and subsequently, auditory cue activates lPBN neurons after fear conditioning. Furthermore, DCN neuron activation can replace the auditory cue but not footshock in fear conditioning. These findings demonstrate that cerebellar nuclei modulate auditory fear conditioning via transmitting conditioned stimuli signals to the lPBN. Collectively, our findings suggest that the DCN-lPBN circuit is a part of neuronal substrates within interconnected brain regions underscoring auditory fear memory.
多个脑区参与经典的恐惧条件反射。尽管有证据表明小脑参与了恐惧条件反射，但小脑输出调节恐惧学习和记忆的机制仍不清楚。我们在小鼠中鉴定出一群具有单突触谷氨酸能投射到外侧臂旁核 (lPBN) 的深部小脑核 (DCN) 神经元 (DCN 神经元)。虽然光遗传学抑制 DCN 神经元会损害听觉恐惧记忆，但 DCN 神经元的激活仅在听觉恐惧条件反射后才会引起冻结行为。此外，听觉恐惧条件反射增强了 DCN-lPBN 突触，随后，恐惧条件反射后，听觉线索激活 lPBN 神经元。此外，DCN 神经元的激活可以取代听觉线索，但不能取代恐惧条件反射中的足底电击。这些发现表明，小脑核通过将条件刺激信号传递到 lPBN 来调节听觉恐惧条件反射。总的来说，我们的发现表明，DCN-lPBN 回路是相互连接的脑区中听觉恐惧记忆的神经元基质的一部分。
