期刊
CELLS
卷 11, 期 24, 页码 -出版社
MDPI
DOI: 10.3390/cells11244019
关键词
hippocampus; learning and memory; contextual fear conditioning; MEN1 rescue; alpha 7 nicotinic receptors; AVV viral transfection; neurons; tamoxifen
类别
Cholinergic neuronal networks in the hippocampus play a crucial role in regulating learning and memory in mammals, and disruptions to these networks are associated with neurodegenerative diseases. This study provides direct evidence that deletion of the MEN1 gene in the CA1 region of the hippocampus leads to deficits in contextual fear conditioning in conditional knockout animals. The study also demonstrates that overexpressing MEN1 can restore this loss of function.
Cholinergic neuronal networks in the hippocampus play a key role in the regulation of learning and memory in mammals. Perturbations of these networks, in turn, underlie neurodegenerative diseases. However, the mechanisms remain largely undefined. We have recently demonstrated that an in vitro MEN1 gene deletion perturbs nicotinic cholinergic plasticity at the hippocampal glutamatergic synapses. Furthermore, MEN1 neuronal conditional knockout in freely behaving animals has also been shown to result in learning and memory deficits, though the evidence remains equivocal. In this study, using an AVV viral vector transcription approach, we provide direct evidence that MEN1 gene deletion in the CA1 region of the hippocampus indeed leads to contextual fear conditioning deficits in conditional knockout animals. This loss of function was, however, recovered when the same animals were re-injected to overexpress MEN1. This study provides the first direct evidence for the sufficiency and necessity of MEN1 in fear conditioning, and further endorses the role of menin in the regulation of cholinergic synaptic machinery in the hippocampus. These data underscore the importance of further exploring and revisiting the cholinergic hypothesis that underlies neurodegenerative diseases that affect learning and memory.
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