Determinants of sparse activity in neocortex

摘要 新皮质神经元的突触可塑性与学习和记忆密切相关。几十年来 对急性脑片的研究已经表征了唤醒所需的尖峰定时的模式 突触的微小变化，但目前尚不清楚这些情况是否会发生 足以驱动活着的大脑中的突触可塑性。事实上，活体记录表明 新皮质神经元生活在一个严重抑制的环境中，从而降低了整体放电 评估和防止可塑性。那么，皮质神经元是如何逃脱这种抑制而遇到 在学习过程中有合适的可塑性条件？新证据表明，小白蛋白 (PV)GABA能神经元可能在调节皮质活动和控制 网络重新布线，特别是在学习的早期阶段。使用多胡须刺激 再加上水的奖励，我们开发了一种感官联想学习的范例 引起小鼠桶状皮质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，新皮质锥体神经元的PV输出在 感觉训练的最早阶段。我们的实验将把活体和急性脑 脑片记录来测试PV神经元是感觉的主要调节器的假设- 小鼠桶状皮质的诱发活动。我们认为与奖励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 在学习过程中的活动。我们的实验将确定大脑皮质去抑制的机制 促进感觉皮层中经验依赖型突触的可塑性。

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.