Colonnese Matthew T, Shen Jing, Murata Yasunobu
Department of Pharmacology and Physiology, Institute for Neuroscience, The George Washington UniversityWashington, DC, United States.
Front Cell Neurosci. 2017 Sep 20;11:289. doi: 10.3389/fncel.2017.00289. eCollection 2017.
Synchronous firing among the elements of forming circuits is critical for stabilization of synapses. Understanding the nature of these local network interactions during development can inform models of circuit formation. Within cortex, spontaneous activity changes throughout development. Unlike the adult, early spontaneous activity occurs in discontinuous population bursts separated by long silent periods, suggesting a high degree of local synchrony. However, whether the micro-patterning of activity within early bursts is unique to this early age and specifically tuned for early development is poorly understood, particularly within the column. To study this we used single-shank multi-electrode array recordings of spontaneous activity in the visual cortex of non-anesthetized neonatal mice to quantify single-unit firing rates, and applied multiple measures of network interaction and synchrony throughout the period of map formation and immediately after eye-opening. We find that despite co-modulation of firing rates on a slow time scale (hundreds of ms), the number of coactive neurons, as well as pair-wise neural spike-rate correlations, are both lower before eye-opening. In fact, on post-natal days (P)6-9 correlated activity was lower than expected by chance, suggesting active decorrelation of activity during early bursts. Neurons in lateral geniculate nucleus developed in an opposite manner, becoming less correlated after eye-opening. Population coupling, a measure of integration in the local network, revealed a population of neurons with particularly strong local coupling present at P6-11, but also an adult-like diversity of coupling at all ages, suggesting that a neuron's identity as locally or distally coupled is determined early. The occurrence probabilities of unique neuronal "words" were largely similar at all ages suggesting that retinal waves drive adult-like patterns of co-activation. These findings suggest that the bursts of spontaneous activity during early visual development do not drive hyper-synchronous activity within columns. Rather, retinal waves provide windows of potential activation during which neurons are active but poorly correlated, adult-like patterns of correlation are achieved soon after eye-opening.
正在形成的神经回路中各元件之间的同步放电对于突触的稳定至关重要。了解发育过程中这些局部网络相互作用的本质可为神经回路形成模型提供依据。在皮质内，自发活动在整个发育过程中会发生变化。与成年期不同，早期自发活动以不连续的群体爆发形式出现，中间间隔很长的静息期，这表明存在高度的局部同步性。然而，早期爆发内活动的微模式是否是这个早期阶段所特有的，并且是否专门针对早期发育进行了调整，目前还知之甚少，尤其是在柱状结构内。为了研究这一点，我们使用单杆多电极阵列记录未麻醉新生小鼠视觉皮质中的自发活动，以量化单个神经元的放电率，并在图谱形成期间和睁眼后立即应用多种网络相互作用和同步性测量方法。我们发现，尽管放电率在缓慢的时间尺度（数百毫秒）上共同调制，但睁眼之前共同激活的神经元数量以及成对神经元的放电率相关性都较低。事实上，在出生后第（P）6 - 9天，相关活动低于随机预期水平，这表明早期爆发期间活动存在主动去相关。外侧膝状核中的神经元则以相反的方式发育，睁眼后相关性降低。群体耦合是局部网络整合的一种测量方法，它揭示了在P6 - 11存在一群具有特别强局部耦合的神经元，但在所有年龄段也都存在类似成年期的耦合多样性，这表明神经元作为局部或远距离耦合的身份在早期就已确定。独特神经元“单词”的出现概率在所有年龄段大致相似，这表明视网膜波驱动类似成年期的共同激活模式。这些发现表明，早期视觉发育期间的自发活动爆发不会驱动柱状结构内的超同步活动。相反，视网膜波提供了潜在激活的窗口，在此期间神经元活跃但相关性较差，类似成年期的相关模式在睁眼后不久就会形成。
