Department of Physiology, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan.
Uonuma Institute of Community Medicine, Niigata University Medical Hospital, Niigata, Japan.
Cereb Cortex. 2019 May 1;29(5):2183-2195. doi: 10.1093/cercor/bhz022.
The hippocampus is functionally heterogeneous between the dorsal and ventral subfields with left-right asymmetry. To determine the possible location of contextual memory, we performed an inhibitory avoidance task to analyze synaptic plasticity using slice patch-clamp technique. The training bilaterally increased the AMPA/NMDA ratio at dorsal CA3-CA1 synapses, whereas the training did not affect the ratio at ventral CA3-CA1 synapses regardless of the hemisphere. Moreover, sequential recording of miniature excitatory postsynaptic currents and miniature inhibitory postsynaptic currents from the same CA1 neuron clearly showed learning-induced synaptic plasticity. In dorsal CA1 neurons, the training dramatically strengthened both excitatory and inhibitory postsynaptic responses in both hemispheres, whereas the training did not promote the plasticity in either hemisphere in ventral CA1 neurons. Nonstationary fluctuation analysis further revealed that the training bilaterally increased the number of AMPA or GABAA receptor channels at dorsal CA1 synapses, but not at ventral CA1 synapses, suggesting functional heterogeneity of learning-induced receptor mobility. Finally, the performance clearly impaired by the bilateral microinjection of plasticity blockers in dorsal, but not ventral CA1 subfields, suggesting a crucial role for contextual learning. The quantification of synaptic diversity in specified CA1 subfields may help us to diagnose and evaluate cognitive disorders at the information level.
海马体在背侧和腹侧亚区之间存在功能异质性,并存在左右不对称性。为了确定情景记忆的可能位置,我们使用切片膜片钳技术进行了抑制性回避任务来分析突触可塑性。双侧训练增加了背侧 CA3-CA1 突触处的 AMPA/NMDA 比值,而无论半球如何,训练都不会影响腹侧 CA3-CA1 突触处的比值。此外,从同一 CA1 神经元进行的微小兴奋性突触后电流和微小抑制性突触后电流的顺序记录清楚地表明了学习诱导的突触可塑性。在背侧 CA1 神经元中,训练显著增强了两个半球的兴奋性和抑制性突触后反应,而在腹侧 CA1 神经元中,训练并未促进任何一个半球的可塑性。非稳态波动分析进一步表明,训练双侧增加了背侧 CA1 突触处的 AMPA 或 GABA A 受体通道的数量,但在腹侧 CA1 突触处没有增加,这表明学习诱导的受体流动性存在功能异质性。最后,在背侧 CA1 亚区而非腹侧 CA1 亚区的双侧微注射可塑性阻滞剂明显损害了性能,这表明情景学习起着至关重要的作用。在特定 CA1 亚区中对突触多样性进行定量分析可能有助于我们在信息水平上诊断和评估认知障碍。