1. Neogenin in Amygdala for Neuronal Activity and Information Processing
- Author
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Anilkumar Pillai, Lin Mei, Lei Xiong, Dong Sun, Yuan Quan Li, Jie Huang, Ya-Nan Wang, Wen Bing Chen, Kai Zhao, Zhaoqi Dong, Shen Ting Zhao, Aiguo Xuan, Jin-Xiu Pan, Wen Cheng Xiong, Xiang Dong Sun, and Hongsheng Wang
- Subjects
Male ,0301 basic medicine ,Mice, Transgenic ,Neurotransmission ,Biology ,Inhibitory postsynaptic potential ,Amygdala ,Mice ,03 medical and health sciences ,Organ Culture Techniques ,0302 clinical medicine ,medicine ,Animals ,Learning ,Research Articles ,Neurons ,Basolateral Nuclear Complex ,General Neuroscience ,Neurogenesis ,Excitatory Postsynaptic Potentials ,Membrane Proteins ,Long-term potentiation ,Fear ,030104 developmental biology ,medicine.anatomical_structure ,nervous system ,Synaptic plasticity ,Excitatory postsynaptic potential ,Neuroscience ,030217 neurology & neurosurgery ,Basolateral amygdala - Abstract
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 maleNeogeninmutant 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 thatNeogeninmutation 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, ablatingNeogeninin 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.SIGNIFICANCE STATEMENTAppropriate neuronal activation in amygdala is critical for information processing. However, the underlying regulatory mechanisms are not well understood. Neogenin is known to regulate axon navigation and adult neurogenesis. Here we show that it is critical for neurotransmission and synaptic plasticity in the amygdala and thus fear memory by using a combination of genetic, electrophysiological, behavioral techniques. Our studies identify a novel function of Neogenin and provide insight into molecular mechanisms of neuronal activation in amygdala for fear processing.
- Published
- 2018