Koranda Jessica L, Masino Susan A, Blaise J Harry
Department of Engineering, Trinity College, Hartford, CT 06106, United States.
J Neurosci Methods. 2008 Jan 30;167(2):160-6. doi: 10.1016/j.jneumeth.2007.08.001. Epub 2007 Aug 7.
There is significant interest in in vivo synaptic plasticity in mice due to the many relevant genetic mutants now available. Nevertheless, use of in vivo models remains limited. To date long-term potentiation (LTP) has been studied infrequently, and long-term depression (LTD) has not been characterized in the mouse in vivo. Herein we describe protocols and improved methodologies we developed to record hippocampal synaptic plasticity reliably from the dentate gyrus of the awake freely behaving mouse. Seven days prior to recording, we implanted microelectrodes encapsulated within a lightweight, low profile head stage assembly. On the day of recording, we induced either LTP or LTD in the awake freely behaving animal, and monitored subsequent changes in population spike amplitude for at least 24h. Using this protocol we attained 80% success in inducing and maintaining either LTP or LTD. Recording from a chronic implant using this improved methodology is best suited to reveal naturally occurring brain activity and avoids both acute effects of local electrode insertion and drifts in neuronal excitability associated with anesthesia. Ultimately a reliable freely behaving mouse model of bi-directional synaptic plasticity is invaluable for full characterization of genetic models of disease states and manipulations of the mechanisms implicated in learning and memory.
由于现在有许多相关的基因变异小鼠，人们对小鼠体内的突触可塑性产生了浓厚兴趣。然而，体内模型的使用仍然有限。到目前为止，长期增强（LTP）很少被研究，而长期抑制（LTD）在小鼠体内尚未得到表征。在此，我们描述了我们开发的方案和改进方法，以从清醒自由活动小鼠的齿状回可靠地记录海马突触可塑性。在记录前7天，我们植入了封装在轻便、低轮廓头部组件内的微电极。在记录当天，我们在清醒自由活动的动物中诱导LTP或LTD，并监测群体峰电位幅度随后至少24小时的变化。使用该方案，我们在诱导和维持LTP或LTD方面取得了80%的成功率。使用这种改进方法从慢性植入物进行记录最适合揭示自然发生的大脑活动，并且避免了局部电极插入的急性效应以及与麻醉相关的神经元兴奋性漂移。最终，一个可靠的双向突触可塑性自由活动小鼠模型对于全面表征疾病状态的遗传模型以及对学习和记忆相关机制的操纵具有重要价值。
