Institute of Molecular Biology and Biotechnology-IMBB, Foundation for Research and Technology-Hellas-FORTH, Heraklion, Crete, Greece.
PLoS Comput Biol. 2012;8(4):e1002489. doi: 10.1371/journal.pcbi.1002489. Epub 2012 Apr 26.
Proper functioning of working memory involves the expression of stimulus-selective persistent activity in pyramidal neurons of the prefrontal cortex (PFC), which refers to neural activity that persists for seconds beyond the end of the stimulus. The mechanisms which PFC pyramidal neurons use to discriminate between preferred vs. neutral inputs at the cellular level are largely unknown. Moreover, the presence of pyramidal cell subtypes with different firing patterns, such as regular spiking and intrinsic bursting, raises the question as to what their distinct role might be in persistent firing in the PFC. Here, we use a compartmental modeling approach to search for discriminatory features in the properties of incoming stimuli to a PFC pyramidal neuron and/or its response that signal which of these stimuli will result in persistent activity emergence. Furthermore, we use our modeling approach to study cell-type specific differences in persistent activity properties, via implementing a regular spiking (RS) and an intrinsic bursting (IB) model neuron. We identify synaptic location within the basal dendrites as a feature of stimulus selectivity. Specifically, persistent activity-inducing stimuli consist of activated synapses that are located more distally from the soma compared to non-inducing stimuli, in both model cells. In addition, the action potential (AP) latency and the first few inter-spike-intervals of the neuronal response can be used to reliably detect inducing vs. non-inducing inputs, suggesting a potential mechanism by which downstream neurons can rapidly decode the upcoming emergence of persistent activity. While the two model neurons did not differ in the coding features of persistent activity emergence, the properties of persistent activity, such as the firing pattern and the duration of temporally-restricted persistent activity were distinct. Collectively, our results pinpoint to specific features of the neuronal response to a given stimulus that code for its ability to induce persistent activity and predict differential roles of RS and IB neurons in persistent activity expression.
工作记忆的正常运作涉及前额叶皮层（PFC）锥体神经元中刺激选择性持续活动的表达，这是指在刺激结束后持续数秒的神经活动。PFC 锥体神经元在细胞水平上区分优先输入与中性输入的机制在很大程度上是未知的。此外，存在具有不同放电模式的锥体细胞亚型，如规则放电和内在爆发，这就提出了它们在 PFC 中持续放电中的独特作用是什么的问题。在这里，我们使用分区建模方法来寻找 PFC 锥体神经元传入刺激及其反应的特性中的鉴别特征，这些特征表明哪些刺激将导致持续活动的出现。此外，我们通过实现规则放电（RS）和内在爆发（IB）模型神经元，使用我们的建模方法来研究持续活动特性中的细胞类型特异性差异。我们确定基底树突内的突触位置是刺激选择性的特征。具体来说，与非诱导刺激相比，在两种模型细胞中，持续活动诱导刺激包含位于远离胞体的更远端的激活突触。此外，动作电位（AP）潜伏期和神经元反应的前几个尖峰间隔时间可用于可靠地检测诱导与非诱导输入，这表明下游神经元可以快速解码即将出现的持续活动的潜在机制。虽然两个模型神经元在持续活动出现的编码特征上没有差异，但持续活动的特性，如放电模式和时间限制的持续活动的持续时间是不同的。总的来说，我们的研究结果确定了特定的神经元对给定刺激的反应特征，这些特征可以对其诱导持续活动的能力进行编码，并预测 RS 和 IB 神经元在持续活动表达中的不同作用。
