Dai Jiaman, Sun Qian-Quan
Department of Zoology and Physiology, University of Wyoming, Laramie, WY82071, USA.
Wyoming Sensory Biology Center of Biomedical Research Excellence, University of Wyoming, Laramie, WY82071, USA.
bioRxiv. 2023 Sep 1:2023.08.30.555603. doi: 10.1101/2023.08.30.555603.
During learning, multi-dimensional inputs are integrated within the sensory cortices. However, the strategies by which the sensory cortex employs to achieve learning remains poorly understood. We studied the sensory cortical neuronal coding of trace eyeblink conditioning (TEC) in head-fixed, freely running mice, where whisker deflection was used as a conditioned stimulus (CS) and an air puff to the cornea delivered after an interval was used as unconditioned stimulus (US). After training, mice learned the task with a set of stereotypical behavioral changes, most prominent ones include prolonged closure of eyelids, and increased reverse running between CS and US onset. The local blockade of the primary somatosensory cortex (S1) activities with muscimol abolished the behavior learning suggesting that S1 is required for the TEC. In naive animals, based on the response properties to the CS and US, identities of the small proportion (~20%) of responsive primary neurons (PNs) were divided into two subtypes: CR (i.e. CS-responsive) and UR neurons (i.e. US-responsive). After animals learned the task, identity of CR and UR neurons changed: while the CR neurons are less responsive to CS, UR neurons gain responsiveness to CS, a new phenomenon we defined as 'learning induced neuronal identity switch (LINIS)'. To explore the potential mechanisms underlying LINIS, we found that systemic and local (i.e. in S1) administration of the nicotinic receptor antagonist during TEC training blocked the LINIS, and concomitantly disrupted the behavior learning. Additionally, we monitored responses of two types of cortical interneurons (INs) and observed that the responses of the somatostatin-expressing (SST), but not parvalbumin-expressing (PV) INs are negatively correlated with the learning performance, suggesting that SST-INs contribute to the LINIS. Thus, we conclude that L2/3 PNs in S1 encode perceptual learning by LINIS like mechanisms, and cholinergic pathways and cortical SST interneurons are involved in the formation of LINIS.
在学习过程中，多维输入在感觉皮层内进行整合。然而，感觉皮层用于实现学习的策略仍知之甚少。我们研究了在头部固定、自由活动的小鼠中追踪眨眼条件反射（TEC）的感觉皮层神经元编码，其中触须偏转用作条件刺激（CS），间隔一段时间后向角膜吹气用作非条件刺激（US）。训练后，小鼠通过一系列刻板的行为变化学会了该任务，最显著的变化包括眼睑长时间闭合，以及在CS和US开始之间反向奔跑增加。用蝇蕈醇对初级体感皮层（S1）活动进行局部阻断消除了行为学习，这表明S1是TEC所必需的。在未训练的动物中，根据对CS和US的反应特性，一小部分（约20%）有反应的初级神经元（PNs）可分为两种亚型：CR（即CS反应性）神经元和UR（即US反应性）神经元。动物学会任务后，CR和UR神经元的特性发生了变化：CR神经元对CS的反应性降低，而UR神经元获得了对CS的反应性，我们将这一新现象定义为“学习诱导的神经元特性转换（LINIS）”。为了探究LINIS潜在的机制，我们发现，在TEC训练期间全身和局部（即S1内）给予烟碱受体拮抗剂可阻断LINIS，并同时破坏行为学习。此外，我们监测了两种类型的皮层中间神经元（INs）的反应，发现表达生长抑素的（SST）而非表达小白蛋白的（PV）INs的反应与学习表现呈负相关，这表明SST-INs对LINIS有作用。因此，我们得出结论，S1中的L2/3 PNs通过类似LINIS的机制编码感知学习，胆碱能通路和皮层SST中间神经元参与LINIS的形成。
