Modulation of coordinated activity across cortical layers by plasticity of inhibitory synapses

In the neocortex, synaptic inhibition shapes all forms of spontaneous and sensory-evoked activity. Importantly, inhibitory transmission is highly plastic, but the functional role of inhibitory synaptic plasticity is unknown. In the mouse barrel cortex, activation of layer (L) 2/3 pyramidal neurons (PNs) elicited strong feed-forward perisomatic inhibition (FFI) onto L5 PNs. We found that FFI involving PV cells was strongly potentiated by postsynaptic PN burst firing. FFI plasticity modified PN excitation-to-inhibition (E/I) ratio, strongly modulated PN gain and altered information transfer across cortical layers. Moreover, our LTPi-inducing protocol modified the firing of L5 PNs and altered the temporal association of PN spikes to γ-oscillations both in vitro and in vivo. All these effects were captured by unbalancing the E/I ratio in a feed-forward inhibition circuit model. Altogether, our results indicate that activity-dependent modulation of perisomatic inhibitory strength effectively influences the participation of single principal cortical neurons to cognitive-relevant network activity. Original Data relative to figures 1-6 and S1-S10在新皮层中，突触抑制塑造了所有形式的自发放电与感觉诱发电活动。值得注意的是，抑制性传递具有高度可塑性，但抑制性突触可塑性的功能作用迄今仍未明确。在小鼠桶状皮层中，激活第2/3层锥体神经元（pyramidal neurons, PNs）可在第5层锥体神经元上诱发强烈的前馈胞周抑制（feed-forward perisomatic inhibition, FFI）。我们发现，包含小白蛋白（parvalbumin, PV）细胞的FFI可通过突触后PN的爆发式放电得到显著增强。FFI可塑性改变了锥体神经元的兴奋-抑制（excitation-to-inhibition, E/I）比值，强烈调控神经元的响应增益，并改变了皮层各层级间的信息传递。此外，我们的抑制性长时程增强（long-term potentiation of inhibition, LTPi）诱导方案，在体外与体内实验中均改变了第5层锥体神经元的放电模式，并调整了锥体神经元锋电位与γ振荡的时间关联。所有上述效应均可在前馈抑制环路模型中，通过失衡E/I比值得以复现。综上，本研究结果表明，活动依赖性的胞周抑制强度调控，可有效影响单个皮层锥体神经元参与认知相关网络活动的能力。本研究的原始数据对应图1-6及补充图S1-S10