División de Neurociencias, Universidad Pablo de Olavide, Sevilla, Spain.
PLoS One. 2011;6(8):e23538. doi: 10.1371/journal.pone.0023538. Epub 2011 Aug 15.
We studied the interactions between short- and long-term plastic changes taking place during the acquisition of a classical eyeblink conditioning and following high-frequency stimulation (HFS) of the reuniens nucleus in behaving mice. Synaptic changes in strength were studied at the reuniens-medial prefrontal cortex (mPFC) and the reuniens-CA1 synapses. Input/output curves and a paired-pulse study enabled determining the functional capabilities of the two synapses and the optimal intensities to be applied at the reuniens nucleus during classical eyeblink conditioning and for HFS applied to the reuniens nucleus. Animals were conditioned using a trace paradigm, with a tone as conditioned stimulus (CS) and an electric shock to the trigeminal nerve as unconditioned stimulus (US). A single pulse was presented to the reuniens nucleus to evoke field EPSPs (fEPSPs) in mPFC and CA1 areas during the CS-US interval. No significant changes in synaptic strength were observed at the reuniens-mPFC and reuniens-CA1 synapses during the acquisition of eyelid conditioned responses (CRs). Two successive HFS sessions carried out during the first two conditioning days decreased the percentage of CRs, without evoking any long-term potentiation (LTP) at the recording sites. HFS of the reuniens nucleus also prevented the proper acquisition of an object discrimination task. A subsequent study revealed that HFS of the reuniens nucleus evoked a significant decrease of paired-pulse facilitation. In conclusion, reuniens nucleus projections to prefrontal and hippocampal circuits seem to participate in the acquisition of associative learning through a mechanism that does not required the development of LTP.
我们研究了在经典眨眼条件反射获得过程中以及在行为小鼠的 reuniens 核高频刺激 (HFS) 后发生的短期和长期塑性变化之间的相互作用。在 reuniens-内侧前额叶皮层 (mPFC) 和 reuniens-CA1 突触处研究了强度的突触变化。输入/输出曲线和成对脉冲研究使我们能够确定两个突触的功能能力以及在经典眨眼条件反射期间应用于 reuniens 核的最佳强度,以及应用于 reuniens 核的 HFS 的最佳强度。动物使用痕迹范式进行条件反射,以音调作为条件刺激 (CS),以三叉神经电击作为非条件刺激 (US)。在 CS-US 间隔期间,向 reuniens 核发送单个脉冲以在 mPFC 和 CA1 区域中诱发电场 EPSPs (fEPSPs)。在获得眼睑条件反射反应 (CR) 期间,在 reuniens-mPFC 和 reuniens-CA1 突触处未观察到突触强度的显著变化。在头两个条件反射日期间进行的两次连续 HFS 会话降低了 CR 的百分比,而在记录部位未引起任何长时程增强 (LTP)。reuniens 核的 HFS 还阻止了物体辨别任务的正确获得。随后的一项研究表明,reuniens 核的 HFS 可引起成对脉冲易化的显著降低。总之,reuniens 核投射到前额叶和海马回路似乎通过不需要 LTP 发展的机制参与联想学习的获得。