Short-Term Plasticity Explains Irregular Persistent Activity in Working Memory Tasks
Short-Term Plasticity Explains Irregular Persistent Activity in Working Memory Tasks
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DOI：
10.1523/jneurosci.3455-12.2013
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发表时间：
2013-01-02
影响因子：
5.3
通讯作者：
Mato, German
中科院分区：
文献类型：
--
作者：
Hansel, David;Mato, German
大脑皮质的持续活动是工作记忆的神经关联。在持续活动中，棘波序列高度不规则，甚至比基线时更多。这一看似无害的特征挑战了我们目前对WM背后的突触机制的理解。在这里，我们认为在WM中，前额叶皮质(PFC)在一种平衡的兴奋和抑制状态下工作，观察到的时间不规则反映了这种状态。我们表明，这要求持续活动的非线性主要存在于PFC神经元之间的神经元相互作用中。我们还表明，短期突触易化可能是这些非线性的生理底物，由此产生的平衡持久活动的机制是强大的，特别是关于连接性的变化。作为例子，我们提出了涉及眼动延迟反应任务的PFC电路的计算模型。这个模型的新奇之处在于，反复出现的兴奋性突触促进了这一过程。我们证明了该模型显示了方向选择性的持续活动。我们发现，即使内存最终会因为异构性而降低，它也可以存储几秒钟，以保证合理的网络大小和连接性。这一模型解释了大量的实验结果，例如，发现持续状态下的放电比基线期间更不规则，神经元反应非常多样化，线索和延迟期的首选方向强烈相关，但调谐宽度不相关。
Persistent activity in cortex is the neural correlate of working memory (WM). In persistent activity, spike trains are highly irregular, even more than in baseline. This seemingly innocuous feature challenges our current understanding of the synaptic mechanisms underlying WM. Here we argue that in WM the prefrontal cortex (PFC) operates in a regime of balanced excitation and inhibition and that the observed temporal irregularity reflects this regime. We show that this requires that nonlinearities underlying the persistent activity are primarily in the neuronal interactions between PFC neurons. We also show that short-term synaptic facilitation can be the physiological substrate of these nonlinearities and that the resulting mechanism of balanced persistent activity is robust, in particular with respect to changes in the connectivity. As an example, we put forward a computational model of the PFC circuit involved in oculomotor delayed response task. The novelty of this model is that recurrent excitatory synapses are facilitating. We demonstrate that this model displays direction-selective persistent activity. We find that, even though the memory eventually degrades because of the heterogeneities, it can be stored for several seconds for plausible network size and connectivity. This model accounts for a large number of experimental findings, such as the findings that have shown that firing is more irregular during the persistent state than during baseline, that the neuronal responses are very diverse, and that the preferred directions during cue and delay periods are strongly correlated but tuning widths are not.