Neogenin in Amygdala for Neuronal Activity and Information Processing
Neogenin in Amygdala for Neuronal Activity and Information Processing
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DOI：
10.1523/jneurosci.0433-18.2018
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发表时间：
2018-10-31
影响因子：
5.3
通讯作者：
Mei, Lin
中科院分区：
文献类型：
--
作者：
Sun, Xiang-Dong;Chen, Wen-Bing;Mei, Lin
恐惧、学习和记忆对生命的生存至关重要，而恐惧、学习和记忆的功能障碍与各种神经精神疾病有关。杏仁核中适当的神经元激活对恐惧记忆至关重要。然而，基本的监管机制并不清楚。再生蛋白是一种DCC（deleted in colorectal cancer）家族受体，在轴突导航和成体神经发生中起重要作用，在基底外侧杏仁核（BLA）的兴奋性神经元中富集。恐惧记忆在雄性再生蛋白突变小鼠中受损。在突变小鼠中，响应于音调提示的恐惧训练的cFos+神经元的数量减少，表明在再生蛋白不存在的情况下异常的神经元活化。电生理学研究表明，再生蛋白突变减少了皮层传入输入BLA锥体神经元，并损害了诱导和维持长时程增强诱发刺激皮层传入，提示再生蛋白在突触可塑性的作用。同时，棘密度和微型兴奋性突触后电流（mEPSC）的频率降低，但微型抑制性突触后电流没有降低，表明再生蛋白在形成兴奋性突触中的作用。最后，切除成年雄性小鼠BLA中的再生蛋白可能通过降低BLA兴奋性神经元中的mEPSC频率来损害恐惧记忆。这些结果揭示了再生蛋白在杏仁核中通过促进和维持神经传递和突触可塑性来进行信息处理的未被认识的功能，并为杏仁核中神经元激活的分子机制提供了见解。
Fear learning and memory are vital for livings to survive, dysfunctions in which have been implicated in various neuropsychiatric disorders. Appropriate neuronal activation in amygdala is critical for fear memory. However, the underlying regulatory mechanisms are not well understood. Here we report that Neogenin, a DCC (deleted in colorectal cancer) family receptor, which plays important roles in axon navigation and adult neurogenesis, is enriched in excitatory neurons in BLA (Basolateral amygdala). Fear memory is impaired in male Neogenin mutant mice. The number of cFos+ neurons in response to tone-cued fear training was reduced in mutant mice, indicating aberrant neuronal activation in the absence of Neogenin. Electrophysiological studies show that Neogenin mutation reduced the cortical afferent input to BLA pyramidal neurons and compromised both induction and maintenance of Long-Term Potentiation evoked by stimulating cortical afferent, suggesting a role of Neogenin in synaptic plasticity. Concomitantly, there was a reduction in spine density and in frequency of miniature excitatory postsynaptic currents (mEPSCs), but not miniature inhibitory postsynaptic currents, suggesting a role of Neogenin in forming excitatory synapses. Finally, ablating Neogenin in the BLA in adult male mice impaired fear memory likely by reducing mEPSC frequency in BLA excitatory neurons. These results reveal an unrecognized function of Neogenin in amygdala for information processing by promoting and maintaining neurotransmission and synaptic plasticity and provide insight into molecular mechanisms of neuronal activation in amygdala.