Kamigaki Tsukasa, Dan Yang
Division of Neurobiology, Department of Molecular and Cell Biology, Helen Wills Neuroscience Institute, Howard Hughes Medical Institute, University of California, Berkeley, California, USA.
Nat Neurosci. 2017 Jun;20(6):854-863. doi: 10.1038/nn.4554. Epub 2017 Apr 24.
Memory-guided behavior requires maintenance of task-relevant information without sensory input, but the underlying circuit mechanism remains unclear. Calcium imaging in mice performing a delayed Go or No-Go task revealed robust delay activity in dorsomedial prefrontal cortex, with different pyramidal neurons signaling Go and No-Go action plans. Inhibiting pyramidal neurons by optogenetically activating somatostatin- or parvalbumin-positive interneurons, even transiently during the delay, impaired task performance, primarily by increasing inappropriate Go responses. In contrast, activating vasoactive intestinal peptide (VIP)-positive interneurons enhanced behavioral performance and neuronal action plan representation. Furthermore, while endogenous activity of somatostatin and parvalbumin neurons was strongly biased toward Go trials, VIP neurons were similarly active in Go and No-Go trials. Somatostatin or VIP neuron activation also impaired or enhanced performance, respectively, in a delayed two-alternative forced-choice task. Thus, dorsomedial prefrontal cortex is a crucial component of the short-term memory network, and activation of its VIP neurons improves memory retention.
记忆引导行为需要在没有感觉输入的情况下维持与任务相关的信息，但其潜在的神经回路机制仍不清楚。对执行延迟“执行-不执行”任务的小鼠进行钙成像显示，背内侧前额叶皮层存在强烈的延迟活动，不同的锥体神经元发出“执行”和“不执行”行动计划的信号。通过光遗传学激活生长抑素或小白蛋白阳性中间神经元来抑制锥体神经元，即使在延迟期间短暂抑制，也会损害任务表现，主要是通过增加不适当的“执行”反应。相反，激活血管活性肠肽（VIP）阳性中间神经元可增强行为表现和神经元行动计划表征。此外，虽然生长抑素和小白蛋白神经元的内源性活动在很大程度上偏向于“执行”试验，但VIP神经元在“执行”和“不执行”试验中的活动相似。在延迟的二选一强制选择任务中，生长抑素或VIP神经元的激活也分别损害或增强了表现。因此，背内侧前额叶皮层是短期记忆网络的关键组成部分，激活其VIP神经元可改善记忆保持。
