Brain Science Institute, Korea Institute of Science and Technology, Seoul, Korea.
Nat Neurosci. 2011 Dec 25;15(2):308-14. doi: 10.1038/nn.2999.
The mediodorsal thalamic nucleus has been implicated in the control of memory processes. However, the underlying neural mechanism remains unclear. Here we provide evidence for bidirectional modulation of fear extinction by the mediodorsal thalamic nucleus. Mice with a knockout or mediodorsal thalamic nucleus-specific knockdown of phospholipase C β4 exhibited impaired fear extinction. Mutant mediodorsal thalamic nucleus neurons in slices showed enhanced burst firing accompanied by increased T-type Ca(2+) currents; blocking of T channels in vivo rescued the fear extinction. Tetrode recordings in freely moving mice revealed that, during extinction, the single-spike (tonic) frequency of mediodorsal thalamic nucleus neurons increased in wild-type mice, but was static in mutant mice. Furthermore, tonic-evoking microstimulations of the mediodorsal thalamic nucleus, contemporaneous with the extinction tones, rescued fear extinction in mutant mice and facilitated it in wild-type mice. In contrast, burst-evoking microstimulation suppressed extinction in wild-type mice, mimicking the mutation. These results suggest that the firing mode of the mediodorsal thalamic nucleus is critical for the modulation of fear extinction.
背内侧丘脑核在记忆过程的控制中起作用。然而，其潜在的神经机制仍不清楚。在这里，我们提供了背内侧丘脑核对恐惧消退进行双向调节的证据。磷脂酶 Cβ4 敲除或背内侧丘脑核特异性敲低的小鼠表现出恐惧消退受损。切片中的突变体背内侧丘脑核神经元表现出增强的爆发放电，伴随着增加的 T 型 Ca(2+)电流；体内阻断 T 型通道可挽救恐惧消退。在自由活动的小鼠中进行的四极管记录显示，在消退期间，野生型小鼠中背内侧丘脑核神经元的单脉冲（紧张性）频率增加，但在突变体小鼠中保持静态。此外，在与消退音同时进行的背内侧丘脑核的紧张性诱发微刺激，挽救了突变体小鼠的恐惧消退，并促进了野生型小鼠的恐惧消退。相比之下，爆发性诱发微刺激抑制了野生型小鼠的消退，模拟了突变。这些结果表明，背内侧丘脑核的放电模式对恐惧消退的调节至关重要。
