Brain Science Institute, Tamagawa Univ., 6-1-1 Tamagawa-gakuen, Machida, Tokyo 194-8610, Japan.
J Neurophysiol. 2012 Sep;108(6):1781-92. doi: 10.1152/jn.00356.2012. Epub 2012 Jun 27.
Stereotaxic head fixation plays a necessary role in current physiological techniques, such as in vivo whole cell recording and two-photon laser-scanning microscopy, that are designed to elucidate the cortical involvement in animal behaviors. In rodents, however, head fixation often inhibits learning and performance of behavioral tasks. In particular, it has been considered inappropriate for head-fixed rodents to be operantly conditioned to perform skilled movements with their forelimb (e.g., lever-press task), despite the potential applicability of the task. Here we have solved this problem conceptually by integrating a lever (operandum) and a rewarding spout (reinforcer) into one ″spout-lever″ device for efficient operant learning. With this device, head-fixed rats reliably learned to perform a pull manipulation of the spout-lever with their right forelimb in response to an auditory cue signal (external-trigger trial, namely, Go trial) within several days. We also demonstrated stable whole cell recordings from motor cortex neurons while the rats were performing forelimb movements in external-trigger trials. We observed a behavior-related increase in the number of action potentials in membrane potential. In the next session, the rats, which had already learned the external-trigger trial, effortlessly performed similar spout-lever manipulation with no cue presentation (internal-trigger trial) additionally. Likewise, some of the rats learned to keep holding the spout-lever in response to another cue signal (No-go trial) in the following session, so that they mastered the Go/No-go discrimination task in one extra day. Our results verified the usefulness of spout-lever manipulation for behavioral experiments employing cutting-edge physiological techniques.
立体定向头部固定在当前的生理技术中起着必要的作用，例如在体全细胞记录和双光子激光扫描显微镜，旨在阐明皮质在动物行为中的作用。然而，在啮齿动物中，头部固定通常会抑制学习和行为任务的表现。特别是，人们认为固定头部的啮齿动物不适合通过操作条件来执行其前肢的熟练运动（例如，压杆任务），尽管该任务具有潜在的适用性。在这里，我们通过将杠杆（操作对象）和奖励喷嘴（强化物）集成到一个“喷嘴-杠杆”装置中，从概念上解决了这个问题，从而实现了有效的操作学习。使用该装置，头部固定的大鼠在几天内可靠地学会了用右前肢拉动喷嘴-杠杆，以响应听觉提示信号（外部触发试验，即 Go 试验）。我们还证明了在大鼠进行外部触发试验时，可以稳定地从运动皮层神经元进行全细胞记录。我们观察到膜电位中的动作电位数量与行为相关增加。在下一个会话中，已经学习了外部触发试验的大鼠无需提示即可毫不费力地进行类似的喷嘴-杠杆操作（内部触发试验）。同样，一些大鼠学会了在另一个提示信号（No-go 试验）出现时保持握持喷嘴-杠杆，因此它们在一天额外的时间内掌握了 Go/No-go 区分任务。我们的结果验证了使用尖端生理技术进行行为实验时喷嘴-杠杆操作的有用性。
