Determinants of sparse activity in neocortex

摘要 新皮层神经元的突触可塑性与学习和记忆密切相关。几十年的 对急性脑切片的研究已经描述了诱发脑电活动所需的尖峰时间模式， 突触变化的细节，但仍然不知道这些条件是否发生， 足以驱动活体大脑中的突触可塑性。事实上，体内记录表明， 新皮层神经元生活在一个深度抑制的环境中， 并阻止可塑性。那么皮层神经元是如何逃脱这种抑制， 在学习过程中的可塑性的适当条件？新的证据表明小清蛋白 (PV)GABA能神经元可能在调节皮层活动和控制神经元活动中起主导作用。 网络重新布线，特别是在学习的早期阶段。使用多须刺激 再加上水的奖励，我们已经开发了一个感官联想学习的范例， 驱动小鼠桶状皮层兴奋性突触强度的快速变化。重要的是我们的 新的数据表明，PV输出到新皮层锥体神经元的显著抑制， 感觉训练的最初阶段。我们的实验将结合在体和急性脑 切片记录来检验PV神经元是感觉的主要调节者的假设， 诱发活动的小鼠桶皮质。我们认为奖赏相关的乙酰胆碱释放 间接抑制PV神经放电以抑制PV输出并增加感觉诱发的 学习期间的活动。我们的实验将确定皮层去抑制的机制， 促进感觉皮层中的经验依赖性突触可塑性。

ABSTRACT Synaptic plasticity in neocortical neurons is intimately tied to learning and memory. Decades of research in acute brain slices have characterized the patterns of spike timing required to evoke synaptic change in minute detail, but it remains unknown whether these conditions occur and are sufficient to drive synaptic plasticity in the living brain. Indeed, in vivo recordings indicate that neocortical neurons live in an environment of profound inhibition that lowers overall firing rates and prevents plasticity. How then do cortical neurons escape this inhibition to encounter appropriate conditions for plasticity during learning? New evidence suggests that parvalbumin (PV) GABAergic neurons may play a dominant role in regulating cortical activity and controlling network rewiring, particularly at the early stages of learning. Using a multiwhisker stimulus coupled to a water reward, we have developed a paradigm for sensory association learning that drives rapid changes in excitatory synaptic strength in mouse barrel cortex. Importantly, our new data indicate that PV output to neocortical pyramidal neurons is markedly suppressed at the earliest stages of sensory training. Our experiments will integrate in vivo and acute brain slice recordings to test the hypothesis that PV neurons are a dominant regulator of sensory- evoked activity in mouse barrel cortex. We propose that reward-related acetylcholine release indirectly suppresses PV neural firing to depress PV output and increase sensory-evoked activity during learning. Our experiments will identify mechanisms for cortical disinhibition that facilitate experience-dependent synaptic plasticity in sensory cortex.