Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.
Optogenetic Stimulation of Prefrontal Glutamatergic Neurons Enhances Recognition Memory.
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DOI：
10.1523/jneurosci.2933-15.2016
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发表时间：
2016-05-04
期刊：
影响因子：
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通讯作者：
Robinson ES
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文献类型：
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作者：
Benn A;Barker GR;Stuart SA;Roloff EV;Teschemacher AG;Warburton EC;Robinson ES
寻找有效的认知增强剂是一个重大的健康挑战;然而，调节海马神经传递有可能提高识别记忆任务的表现。先前使用谷氨酸受体拮抗剂的研究表明，内侧前额叶皮层（mPFC）在联想识别记忆中起着核心作用。本研究采用光遗传学方法，以啮齿类动物mPFC内的海马能神经元为靶点，研究短时识别记忆。在正常动物中，选择性刺激海马能神经元在信息在线维持期间增强联想识别记忆。这种认知增强作用通过局部输注AMPakine CX 516而不是CX 546来复制，其对EPSP的作用不同。这表明，增强兴奋性突触电流的幅度，而不是持续时间，提高记忆性能。通过输注mGluR 7突触前受体拮抗剂MMPIP增加谷氨酸释放对性能没有影响。这些结果提供了新的机制信息，可以指导未来的认知增强剂的靶向。我们的工作表明，通过选择性地使用光遗传学方法增强内源性海马神经元活性，可以实现改善的联想识别记忆。基于这些观察，我们使用增强EPSP振幅的药物治疗来概括这种效应;然而，改变EPSP持续时间或增加谷氨酸释放的药物缺乏疗效。这表明，神经和时间特异性都需要实现认知增强。
Finding effective cognitive enhancers is a major health challenge; however, modulating glutamatergic neurotransmission has the potential to enhance performance in recognition memory tasks. Previous studies using glutamate receptor antagonists have revealed that the medial prefrontal cortex (mPFC) plays a central role in associative recognition memory. The present study investigates short-term recognition memory using optogenetics to target glutamatergic neurons within the rodent mPFC specifically. Selective stimulation of glutamatergic neurons during the online maintenance of information enhanced associative recognition memory in normal animals. This cognitive enhancing effect was replicated by local infusions of the AMPAkine CX516, but not CX546, which differ in their effects on EPSPs. This suggests that enhancing the amplitude, but not the duration, of excitatory synaptic currents improves memory performance. Increasing glutamate release through infusions of the mGluR7 presynaptic receptor antagonist MMPIP had no effect on performance. SIGNIFICANCE STATEMENT These results provide new mechanistic information that could guide the targeting of future cognitive enhancers. Our work suggests that improved associative-recognition memory can be achieved by enhancing endogenous glutamatergic neuronal activity selectively using an optogenetic approach. We build on these observations to recapitulate this effect using drug treatments that enhance the amplitude of EPSPs; however, drugs that alter the duration of the EPSP or increase glutamate release lack efficacy. This suggests that both neural and temporal specificity are needed to achieve cognitive enhancement.