Walcott E C, Langdon R B
The Neurosciences Institute, 10640 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Neuroscience. 2002;112(4):815-26. doi: 10.1016/s0306-4522(02)00131-8.
Recently, variation upon a well-established hippocampal model has given rise to a new paradigm in which the strength of synaptic inputs to neocortical layer 2/3 is estimated in vitro by recording synaptically driven extracellular potentials elicited there by electrical stimulation applied to underlying layer 4. The analysis of these potentials is commonly based upon an assumption that postsynaptic spiking has played no significant role in their generation. Here, we have tested this assumption by quantifying in rats (using data obtained by cell-attached recording) the rate at which unit spikes are elicited in layer 2/3 under commonly used conditions of stimulation and recording. We found that spike responses were regularly elicited at the same latencies as field potential peaks and the rising phases of intracellularly recorded synaptic currents, and the incidence of such spiking (the fractional rate of cells spiking versus cells sampled) was sufficient to give this higher-order activity a major role in determining response amplitudes. We then analyzed layer 2/3 waveform characteristics before and after inducing long-term potentiation (LTP) by theta-burst stimulation (TBS) and found that the induction of LTP succeeded only when the initial response included a strong spike component. We further observed that LTP expression was always accompanied by a pronounced enhancement of such components. Our data suggest that, unlike in hippocampal CA1, LTP elicited by TBS in this neocortical paradigm depends upon modification of synaptically driven spike activity, through either enhanced synchronization of unitary responses, the recruitment of additional responding units, or both. This potentiation of the spike response could arise (as previously proposed) through an increase in the efficacy of synapses mediating projection from layer 4 to 2/3, but other mechanisms may also contribute, such as modification of short-range recurrent connections within layer 2/3, which are likely to play an important role in defining local-network cell ensembles.
最近，对一个成熟的海马体模型进行的改进催生了一种新的范式，即在体外通过记录施加于下层4的电刺激在新皮层2/3层引发的突触驱动细胞外电位，来估计输入到该层的突触强度。对这些电位的分析通常基于一个假设，即突触后放电在其产生过程中没有发挥重要作用。在这里，我们通过在大鼠中进行量化（使用细胞贴附记录获得的数据），测试了这一假设，即在常用的刺激和记录条件下，2/3层中单位放电的诱发率。我们发现，放电反应在与场电位峰值和细胞内记录的突触电流上升阶段相同的潜伏期有规律地诱发，并且这种放电的发生率（放电细胞与采样细胞的分数率）足以使这种高阶活动在决定反应幅度中起主要作用。然后，我们分析了通过θ波爆发刺激（TBS）诱导长时程增强（LTP）前后2/3层的波形特征，发现只有当初始反应包括强烈的放电成分时，LTP的诱导才会成功。我们进一步观察到，LTP的表达总是伴随着这些成分的显著增强。我们的数据表明，与海马体CA1区不同，在这种新皮层范式中，由TBS诱发的LTP依赖于突触驱动的放电活动修饰，这可能是通过增强单一反应的同步性、招募额外的反应单位，或两者兼而有之。这种放电反应的增强可能（如先前提出的）是通过增加介导从第4层到2/3层投射的突触效能而产生的，但其他机制也可能起作用，如2/3层内短程递归连接的修饰，这可能在定义局部网络细胞集合中起重要作用。
