LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits.
LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits.
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LRRTM3调节拓扑连接的海马神经回路中突触特性的活性依赖性同步。
DOI：
10.1073/pnas.2110196119
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发表时间：
2022-01-18
影响因子：
11.1
通讯作者：
Ko J
中科院分区：
文献类型：
--
作者：
Kim J;Park D;Seo NY;Yoon TH;Kim GH;Lee SH;Seo J;Um JW;Lee KJ;Ko J
本研究使用常规和条件性Lrrtm 3-KO小鼠，利用成像、电生理学和三维高分辨率电子显微镜分析来研究LRRTM 3在体内的神经回路作用。我们发现LRRTM 3是齿状回突触的内侧穿通通路的特异性组装和功能所必需的。此外，LRRTM 3是苔藓纤维-CA 3突触的适当兴奋性突触连接和长期突触可塑性所必需的。引人注目的是，内侧穿通通路-齿状回（MPP-DG）回路活动的突触前失活完全挽救了Lrrtm 3-KO小鼠受损的兴奋性突触输入和长期突触可塑性，表明LRRTM 3参与了活动依赖性海马兴奋性突触的细化/稳定，这是由海马能神经传递决定和同步的。突触细胞粘附分子（CAM）组织神经回路的结构和性能。然而，突触CAM是否参与特定神经回路的活动依赖性重塑尚不完全清楚。富含亮氨酸重复跨膜蛋白3（LRRTM 3）是海马齿状回（DG）颗粒神经元兴奋性突触发育所必需的。在这里，我们报告说，Lrrtm 3缺陷小鼠表现出选择性减少兴奋性突触密度和突触强度的预测涉及内侧内嗅皮层（MEC）和DG颗粒神经元，伴随着增加神经递质释放和减少颗粒神经元的兴奋性。LRRTM 3缺失显著减少DG颗粒神经元的海马苔藓纤维（Mf）对海马CA 3神经元中的多刺赘生物的兴奋性突触神经支配。此外，DG神经元中的LRRTM 3损失显著降低苔藓纤维长时程增强（Mf-LTP）。值得注意的是，沉默MEC-DG电路保护DG和CA 3神经元的兴奋性突触输入减少，DG颗粒神经元的兴奋性，和Lrrtm 3缺陷小鼠的Mf-LTP。这些结果表明LRRTM 3可能是MEC-DG-CA 3兴奋性突触连接拓扑结构的活动依赖性同步化的关键因素。总的来说，我们的数据表明，LRRTM 3形状的特定海马电路的目标特定的结构和功能特性。
The present study utilized imaging, electrophysiology, and three-dimensional high-resolution electron microscopy analyses to address the neural circuit role of LRRTM3 in vivo, using both conventional and conditional Lrrtm3-KO mice. We found that LRRTM3 is required for the specific assembly and function of the medial perforant path to dentate gyrus synapses. Moreover, LRRTM3 is required for proper excitatory synaptic connectivity and long-term synaptic plasticity at mossy fiber–CA3 synapses. Strikingly, presynaptic inactivation of medial perforant path–dentate gyrus (MPP–DG) circuit activities completely rescued the impaired excitatory synaptic inputs and long-term synaptic plasticity of Lrrtm3-KO mice, demonstrating that LRRTM3 is involved in activity-dependent hippocampal excitatory synapse refinement/stabilization, which is dictated and synchronized by glutamatergic neurotransmission. Synaptic cell-adhesion molecules (CAMs) organize the architecture and properties of neural circuits. However, whether synaptic CAMs are involved in activity-dependent remodeling of specific neural circuits is incompletely understood. Leucine-rich repeat transmembrane protein 3 (LRRTM3) is required for the excitatory synapse development of hippocampal dentate gyrus (DG) granule neurons. Here, we report that Lrrtm3-deficient mice exhibit selective reductions in excitatory synapse density and synaptic strength in projections involving the medial entorhinal cortex (MEC) and DG granule neurons, accompanied by increased neurotransmitter release and decreased excitability of granule neurons. LRRTM3 deletion significantly reduced excitatory synaptic innervation of hippocampal mossy fibers (Mf) of DG granule neurons onto thorny excrescences in hippocampal CA3 neurons. Moreover, LRRTM3 loss in DG neurons significantly decreased mossy fiber long-term potentiation (Mf-LTP). Remarkably, silencing MEC–DG circuits protected against the decrease in the excitatory synaptic inputs onto DG and CA3 neurons, excitability of DG granule neurons, and Mf-LTP in Lrrtm3-deficient mice. These results suggest that LRRTM3 may be a critical factor in activity-dependent synchronization of the topography of MEC–DG–CA3 excitatory synaptic connections. Collectively, our data propose that LRRTM3 shapes the target-specific structural and functional properties of specific hippocampal circuits.
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影响因子：
64.8
作者：
Berns DS;DeNardo LA;Pederick DT;Luo L
通讯作者：
Luo L
影响因子：
16.2
作者：
Ko, Jaewon;Fuccillo, Marc V.;Malenka, Robert C.;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
5.3
作者：
Bernier, Brian E.;Lacagnina, Anthony F.;Drew, Michael R.
通讯作者：
Drew, Michael R.
影响因子：
2.5
作者：
AMARAL, DG;DENT, JA
通讯作者：
DENT, JA
影响因子：
3.5
作者：
Chierzi, Sabrina;Stachniak, Tevye J.;Murai, Keith K.
通讯作者：
Murai, Keith K.