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Abstract：
Theta oscillations in the hippocampal local field potential (LFP) appear during translational movement and arousal, modulate the activity of principal cells, and are associated with spatial cognition and episodic memory function. All known anxiolytics slightly but consistently reduce hippocampal theta frequency. However, whether this electrophysiological effect is mechanistically related to the decreased behavioral expression of anxiety is currently unclear. Here, we propose that a reduction in theta frequency affects synaptic plasticity and mnemonic function and that this can explain the reduction in anxiety behavior. We test this hypothesis in a biophysical model of contextual fear conditioning. First, we confirm that our model reproduces previous empirical results regarding the dependence of synaptic plasticity on presynaptic firing rate. Next, we investigate how theta frequency during contextual conditioning impacts learning. These simulations demonstrate that learned associations between threat and context are attenuated when learning takes place under reduced theta frequency. Additionally, our simulations demonstrate that learned associations result in increased theta activity in the amygdala, consistent with empirical data. In summary, we propose a mechanism that can account for the behavioral effect of anxiolytics by impairing the integration of threat attributes of an environment into the cognitive map due to reduced synaptic potentiation.
摘要：
海马局部场电位（LFP）的θ振荡出现在平移运动和唤醒过程中，调节主细胞的活性，并与空间认知和情景记忆功能有关。所有已知的抗焦虑药都会略微但始终降低海马θ频率。然而,目前尚不清楚这种电生理效应是否与焦虑的行为表达减少有机制关系.这里,我们认为theta频率的降低会影响突触可塑性和记忆功能，这可以解释焦虑行为的减少。我们在上下文恐惧条件的生物物理模型中检验了这一假设。首先,我们证实，我们的模型再现了先前关于突触可塑性对突触前放电率依赖性的经验结果。接下来,我们研究了在语境条件下theta频率如何影响学习。这些模拟表明，当学习在降低的theta频率下进行时，威胁和上下文之间的学习关联会减弱。此外,我们的模拟表明，学习关联导致杏仁核theta活性增加，与经验数据一致。总之,我们提出了一种机制，该机制可以通过减少突触增强而损害环境的威胁属性到认知图的整合来解释抗焦虑药的行为效应。
