Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV 26506;
Department of Neuroscience, West Virginia University School of Medicine, Morgantown, WV 26506.
Proc Natl Acad Sci U S A. 2018 Oct 2;115(40):E9419-E9428. doi: 10.1073/pnas.1808539115. Epub 2018 Aug 28.
Previous studies have shown changes in membrane properties of neurons in rat deep cerebellar nuclei (DCN) as a function of development, but due to technical difficulties in obtaining viable DCN slices from adult animals, it remains unclear whether there are learning-related alterations in the membrane properties of DCN neurons in adult rats. This study was designed to record from identified DCN cells in cerebellar slices from postnatal day 25-26 (P25-26) rats that had a relatively mature sensory nervous system and were able to acquire learning as a result of tone-shock eyeblink conditioning (EBC) and to document resulting changes in electrophysiological properties. After electromyographic electrode implantation at P21 and inoculation with a fluorescent pseudorabies virus (PRV-152) at P22-23, rats received either four sessions of paired delay EBC or unpaired stimulus presentations with a tone conditioned stimulus and a shock unconditioned stimulus or sat in the training chamber without stimulus presentations. Compared with rats given unpaired stimuli or no stimulus presentations, rats given paired EBC showed an increase in conditioned responses across sessions. Whole-cell recordings of both fluorescent and nonfluorescent DCN projection neurons showed that delay EBC induced significant changes in membrane properties of evoked DCN action potentials including a reduced after-hyperpolarization amplitude and shortened latency. Similar findings were obtained in hyperpolarization-induced rebound spikes of DCN neurons. In sum, delay EBC produced significant changes in the membrane properties of juvenile rat DCN projection neurons. These learning-specific changes in DCN excitability have not previously been reported in any species or task.
先前的研究表明，大鼠小脑深部核（DCN）神经元的膜特性会随发育而发生变化，但由于从成年动物获得可存活的 DCN 切片存在技术困难，因此尚不清楚成年大鼠 DCN 神经元的膜特性是否存在与学习相关的改变。本研究旨在记录来自出生后第 25-26 天（P25-26）大鼠小脑切片中已识别的 DCN 细胞，这些大鼠具有相对成熟的感觉神经系统，并且能够通过音调-电击眨眼条件反射（EBC）进行学习，并记录由此产生的电生理特性变化。在 P21 时植入肌电图电极，并在 P22-23 时接种荧光单纯疱疹病毒（PRV-152）后，大鼠接受了 4 次配对延迟 EBC 或非配对刺激呈现，其中包括音调条件刺激和电击非条件刺激，或者在没有刺激呈现的情况下坐在训练室中。与接受非配对刺激或无刺激呈现的大鼠相比，接受配对 EBC 的大鼠在整个训练过程中表现出条件反应的增加。对荧光和非荧光 DCN 投射神经元的全细胞记录显示，延迟 EBC 诱导诱发的 DCN 动作电位的膜特性发生了显著变化，包括后超极化幅度减小和潜伏期缩短。DCN 神经元的超极化诱发反弹峰也有类似的发现。总之，延迟 EBC 导致幼年大鼠 DCN 投射神经元的膜特性发生了显著变化。在任何物种或任务中，以前都没有报道过 DCN 兴奋性的这种学习特异性变化。
