学习运动技能通过单颗粒到达任务小鼠学习
Summary
持续练习提高协调运动的精度。在这里，我们介绍一种单颗粒深远的任务，其目的是评估在小鼠的学习和前肢的记忆技能。
Abstract
为达到和检索对象需要精确和协调运动动作中的前肢。当小鼠被反复训练来掌握和持久性的训练之后取回定位在特定位置的食物奖励，其机动性能（定义为精度和速度）随时间逐步提高，并且台地。一旦达到这样的功力被掌握，其进一步维护不需要不断的实践。在这里，我们介绍一种单颗粒深远的任务，研究技术前肢运动小鼠的获取和维护。在这段视频中，我们首先描述小鼠被在此学习和记忆范式经常遇到的行为，然后讨论如何分类这些行为并量化观察到的结果。结合小鼠遗传学，这种模式可以用来作为一种行为的平台，探索解剖基础，生理特性，以及学习和记忆的分子机制。
Introduction
了解底层机制的学习和记忆是神经科学中最大的挑战之一。在电机系统，购置新的运 动技能和实践通常被称为运动学习，而先前学到运动技能的保留被视为运动记忆1。学习一项新的运动技能通常是体现在改善所需的电机性能随着时间的推移，直到当运动技能要么是完善还是令人满意的一致点。在大多数情况下，所获取的运动记忆可以持续相当长的时间周期，即使是在没有实践的。在人类中，利用正电子发射断层扫描（PET）和功能磁共振成像（fMRI）的神经影像学研究表明，初级运动皮层（M1）的活性变化过程中运动技能学习2-4的采集阶段，并通过货币供应量M1的活动临时干预低频经颅磁刺激导致显ficantly打乱保留马达改善行为5。同样地，前肢特定训练对大鼠诱导功能和解剖可塑性中的货币供应量M1，在M1高速公路对侧前肢训练两者的c-fos基因的活性和突触/神经元的比例在运动技能学习6的后期增加例证。此外，类似的训练模式也加强层在对侧M1三分之二水平连接对应于训练的前肢，从而降低了长时程增强（LTP）和增强长期抑制（LTD）大鼠获得的任务7之后。例如突触修饰，然而，没有在对应于未受过训练的前肢或后肢8的M1皮层区域观察到。或者，当M 1是通过笔划损坏，有在前肢特定电动机技能9戏剧性的缺陷。虽然大多数电动机行为研究已经在人类，猴子进行s和大鼠2-8,10-17，小鼠会因为其强大的遗传学和低成本的一个有吸引力的模型系统。
在这里，我们提出了一个具体的前肢运动技能学习范式：单颗粒深远的任务。在这个范例中，老鼠被训练通过一个狭窄的缝隙的前肢伸到把握和检索定位在一个固定的位置，类似于学习射箭，飞镖投掷，射击和篮球在人类行为的食物颗粒（小米）。这达到了任务已经被修改已显示出小鼠和大鼠18之间类似的结果以前的大鼠的研究。利用双光子成像颅，我们以前的工作一直遵循的树突棘（多数为兴奋性突触的突触后结构）随时间的动态这次培训过程中。我们发现，一个单一的训练导致的锥体神经元新的树突棘的运动皮层对侧前肢训练迅速出现。 S同样深远的任务ubsequent培训优先稳定这些学习引起的刺，它坚持很久以后的训练结束19。此外，在达到任务的重复涌现刺倾向于沿着树突聚集，而串联到达执行任务，另一前肢专用电机的任务（ 即面食处理任务）过程中形成的刺没有集群20。
在本视频中，我们描述了一步一步的这种行为模式的设置，从最初的食品匮乏到整形，并以动作训练。我们还描述了小鼠的一般行为执行该行为范式的过程中，以及如何将这些行为进行分类和分析。最后，我们讨论到实践这样的学习模式所需的预防措施，并可能在数据分析中遇到的问题。
Protocol
Representative Results
Discussion
重要的塑造阶段：
因为从一个未知的环境是增加焦虑，它通常是困难的小鼠在新环境中21,22的培训。因此，整形的目的是熟悉小鼠的培训室，培训师（ 即降低他们的焦虑程度），任务要求（ 即识别种子作为食物源）。成形的另一个目标是确定为未来训练个体小鼠的优选的肢体。塑造过程中，至关重要的是，小鼠未过形，因为它可以提供多余的“深远的练?…
Offenlegungen
The authors have nothing to disclose.
Acknowledgements
这项工作是由精神卫生研究所授予（1R01MH094449-01A1）以YZ
Materials
| Training chamber in clear acrylic box | For dimensions, see Fig. 1A |
| Tilted tray for shaping | custom-made from glass slides, see Fig. 1B |
| Food platform for training | For dimensions, see Fig. 1C |
| Millet seeds | filtered from “Wild Bird Food Dove and Quail Blend Wild Bird Food (All Living Things) |
| Forceps | For placing the seeds |
| A weighing scale | For daily body weight measurement |
| A stopwatch | For time measurement during shaping/training sessions |
Referenzen
- Schmidt, R. A. Motor Learning Principles for Physical Therapy. Foundations for Physical Therapy. Contemporary Management of Motor Control Problems, Proceedings of the II STEP Conference. , 49-63 (1991).
- Honda, M., Deiber, M. P., Ibanez, V., Pascual-Leone, A., Zhuang, P., Hallett, M. Dynamic cortical involvement in implicit and explicit motor sequence learning. A PET study.. Brain. 121, 2159-2173 (1998).
- Karni, A., Meyer, G., Jezzard, P., Adams, M. M., Turner, R., Ungerleider, L. G. Functional MRI evidence for adult motor cortex plasticity during motor skill learning. Nature. 377, 155-158 (1995).
- Karni, A., et al. The acquisition of skilled motor performance: fast and slow experience-driven changes in primary motor cortex. Proc. Natl Acad. Sci. U.S.A. 95, 861-868 (1998).
- Muellbacher, W., et al. Early consolidation in human primary motor cortex. Nature. 415, 640-644 (2002).
- Kleim, J. A., Hogg, T. M., VandenBerg, P. M., Cooper, N. R., Bruneau, R., Remple, M. Cortical synaptogenesis and motor map reorganization occur during late, but not early, phase of motor skill learning. J. Neurosci. 24, 628-633 (2004).
- Rioult-Pedotti, M. S., Friedman, D., Donoghue, J. P. Learning-induced LTP in neocortex. Science. 290, 533-536 (2000).
- Rioult-Pedotti, M. S., Friedman, D., Hess, G., Donoghue, J. P. Strengthening of horizontal cortical connections following skill learning. Nat. Neurosci. 1, 230-234 (1998).
- Farr, T. D., Whishaw, I. Q. Quantitative and qualitative impairments in skilled reaching in the mouse (Mus musculus) after a focal motor cortex stroke. Stroke J. Cereb. Circ. 33, 1869-1875 (2002).
- Huang, V. S., Haith, A., Mazzoni, P., Krakauer, J. W. Rethinking motor learning and savings in adaptation paradigms: model-free memory for successful actions combines with internal models. Neuron. 70, 787-801 (2011).
- Smith, M. A., Ghazizadeh, A., Shadmehr, R. Interacting adaptive processes with different timescales underlie short-term motor learning. PLoS Biol. 4, (2006).
- Pavlides, C., Miyashita, E., Asanuma, H. Projection from the sensory to the motor cortex is important in learning motor skills in the monkey. J. Neurophysiol. 70, 733-741 (1993).
- Paz, R., Boraud, T., Natan, C., Bergman, H., Vaadia, E. Preparatory activity in motor cortex reflects learning of local visuomotor skills. Nat. Neurosci. 6, 882-890 (2003).
- Paz, R., Vaadia, E. Learning-induced improvement in encoding and decoding of specific movement directions by neurons in the primary motor cortex. PLoS Biol. 2, (2004).
- Plautz, E. J., Milliken, G. W., Nudo, R. J. Effects of repetitive motor training on movement representations in adult squirrel monkeys: role of use versus learning. Neurobiol. Learn. Mem. 74, 27-55 (2000).
- Hosp, J. A., Pekanovic, A., Rioult-Pedotti, M. S., Luft, A. R. Dopaminergic projections from midbrain to primary motor cortex mediate motor skill learning. J. Neurosci. 31, 2481-2487 (2011).
- Adkins, D. L., Boychuk, J., Remple, M. S., Kleim, J. A. Motor training induces experience-specific patterns of plasticity across motor cortex and spinal cord. 101, 1776-1782 (2006).
- Whishaw, I. Q. An endpoint, descriptive, and kinematic comparison of skilled reaching in mice (Mus musculus) with rats (Rattus norvegicus). Behav. Brain Res. 78, 101-111 (1996).
- Xu, T., et al. Rapid formation and selective stabilization of synapses for enduring motor memories. Nature. 462, 915-919 (2009).
- Fu, M., Yu, X., Lu, J., Zuo, Y. Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature. 483, 92-95 (2012).
- Whishaw, I. Q., Whishaw, P., Gorny, B. The structure of skilled forelimb reaching in the rat: a movement rating scale. J .Vis. Exp. , (2008).
- Bailey, K. R., Crawley, J. N. Anxiety-Related Behavior in Mice. In Buccafusco JJ (Ed.) Methods of Behavior Analysis in Neuroscience. Chapter 5, 2nd ed. , (2009).
- Yu, X., Zuo, Y. Spine plasticity in the motor cortex. Curr. Opin. Neurobiol. 21, 169-174 (2011).
- Qian, Y., Chen, M., Forssberg, H., Diaz Heijtz, R. Genetic variation in dopamine-related gene expression influences motor skill learning in mice. Genes Brain Behav. 12, 604-614 (2013).
- MacLellan, C. L., Gyawali, S., Colbourne, F. Skilled reaching impairments follow intrastriatal hemorrhagic stroke in rats. Behav. Brain Res. 175, 82-89 (2006).
- Hong, S. M., et al. Reduced hippocampal neurogenesis and skill reaching performance in adult Emx1 mutant mice. Exp. Neurol. 206, 24-32 (2007).
- Bureau, G., Carrier, M., Lebel, M., Cyr, M. Intrastriatal inhibition of extracellular signal-regulated kinases impaired the consolidation phase of motor skill learning. Neurobiol. Learn. Mem. 94, 107-115 (2010).
- McCormick, D. A., Lavond, D. G., Thompson, R. F. Neuronal responses of the rabbit brainstem during performance of the classically conditioned nictitating membrane (NM)/eyelid response. Brain Res. 271, 73-88 (1983).
- Molinari, M., et al. Cerebellum and procedural learning: evidence from focal cerebellar lesions. Brain. 120, 1753-1762 (1997).
- Willuhn, I., Steiner, H. Motor-skill learning in a novel running-wheel task is dependent on D1 dopamine receptors in the striatum. Neurowissenschaften. 153, 249-258 (2008).
