Neurobiology Research Unit, Okinawa Institute of Science and Technology (OIST), Okinawa, Japan.
PLoS Comput Biol. 2013 Apr;9(4):e1002954. doi: 10.1371/journal.pcbi.1002954. Epub 2013 Apr 11.
Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of 10 ~ 20% and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around 15% connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics - it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is optimized to generate stimulus dependent activity patterns for long periods after variations in cortical excitation.
纹状体(基底神经节的主要输入结构)中的缓慢变化活动对于运动序列的学习和执行很重要。纹状体中间神经元(MSN)形成细胞集合,其群体放电率在慢行为相关时间尺度上相干地变化。已经表明,这种活动出现在局部 MSN 网络模型中,但仅在 10 到 20%的实际连接性下,并且仅当 MSN 产生的抑制性突触后电位(IPSP)具有实际大小时才出现。在这里,我们提出了一个原因。我们研究了 MSN 网络生成的群体活动如何与随时间变化的皮质驱动活动相互作用,就像在行为任务中那样。我们发现,在不切实际的高连接性下,会发现一个稳定的胜者通吃类型的状态,其中网络活动分为固定刺激相关的规则发射和静止组件。在这种状态下,只有少数群体放电率组件与皮质刺激变化相互作用。在大约 15%的连接性下,会发生向更动态活跃状态的转变,其中所有细胞都会不断在活动和静止之间切换。在这个低连接性状态下,MSN 群体组件随机漫游,并且与皮质驱动的变化也无关。只有在过渡状态下,皮质驱动的微弱变化才会与许多群体组件相互作用,从而在刺激开始后数百毫秒内可重复地激活序列细胞集合,并且在时程直方图中显示出强烈的刺激和时间特异性。我们表明,令人惊讶的是,这种活动在纹状体实际连接性和 IPSP 大小下最大化。因此,我们认为局部 MSN 网络具有最佳特性 - 它既不会过于稳定而无法以动态复杂的方式对皮质变化做出反应,也不会过于不稳定而无法以一致的可重复方式做出反应。相反,它是优化的,以便在皮质兴奋变化后很长一段时间内产生与刺激相关的活动模式。