Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.

IF 6.2 2区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cell and Bioscience Pub Date : 2025-08-12 DOI:10.1186/s13578-025-01458-y

Nicola Brandt, Arne Battefeld, Olga Suckau, Konstantin Stadler, Bhumika Singh, Pei Zhang, Junken Aoki, Jerold Chun, Christian Henneberger, Rosemarie Grantyn, Johannes Vogt, Robert Nitsch, Ulf Strauss, Anja U Bräuer

{"title":"Lysophosphatidic acid selectively modulates excitatory transmission in hippocampal neurons.","authors":"Nicola Brandt, Arne Battefeld, Olga Suckau, Konstantin Stadler, Bhumika Singh, Pei Zhang, Junken Aoki, Jerold Chun, Christian Henneberger, Rosemarie Grantyn, Johannes Vogt, Robert Nitsch, Ulf Strauss, Anja U Bräuer","doi":"10.1186/s13578-025-01458-y","DOIUrl":null,"url":null,"abstract":"Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid that affects hippocampal excitatory synaptic transmission.Results: Here we provide in vitro evidence that LPA elicits intracellular calcium concentration ([Ca2+]i) transients by LPA2 receptor activation in primary cultured hippocampal mouse neurons. Downstream and via Gi-coupling, this led to phospholipase C (PLC) activation, inositol (1,4,5) trisphosphate (IP3)-induced Ca2+ release (IICR) and voltage gated Ca2+ channel activation. In addition, we found that LPA elevated [Ca2+]i, not only in the soma but also in presynaptic terminals. This altered the frequency of spontaneous vesicle release specifically in excitatory synapses. However, against our expectations, LPA reduced the frequency of miniature excitatory postsynaptic currents. This was due to a depletion of releasable vesicles resulting from a slowed recycling. SynaptopHluorin based measurements indicated a transient augmentation of release followed by prolonged persistence of vesicles at the membrane. Concordant to our previous findings on ex vivo brain slices, LPA increased spontaneous glutamatergic vesicle release in Banker style astrocytic co-cultures. Our results indicate that pro-excitatory LPA effects critically depend on stable vesicle pools.Conclusions: Taken together, our data further support membrane derived phospholipids as active modulators of excitatory synaptic transmission.","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"117"},"PeriodicalIF":6.2000,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12341218/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-025-01458-y","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Lysophosphatidic acid (LPA) is a bioactive phospholipid that affects hippocampal excitatory synaptic transmission.

Results: Here we provide in vitro evidence that LPA elicits intracellular calcium concentration ([Ca²⁺]_i) transients by LPA₂ receptor activation in primary cultured hippocampal mouse neurons. Downstream and via G_i-coupling, this led to phospholipase C (PLC) activation, inositol (1,4,5) trisphosphate (IP₃)-induced Ca²⁺ release (IICR) and voltage gated Ca²⁺ channel activation. In addition, we found that LPA elevated [Ca²⁺]_i, not only in the soma but also in presynaptic terminals. This altered the frequency of spontaneous vesicle release specifically in excitatory synapses. However, against our expectations, LPA reduced the frequency of miniature excitatory postsynaptic currents. This was due to a depletion of releasable vesicles resulting from a slowed recycling. SynaptopHluorin based measurements indicated a transient augmentation of release followed by prolonged persistence of vesicles at the membrane. Concordant to our previous findings on ex vivo brain slices, LPA increased spontaneous glutamatergic vesicle release in Banker style astrocytic co-cultures. Our results indicate that pro-excitatory LPA effects critically depend on stable vesicle pools.

Conclusions: Taken together, our data further support membrane derived phospholipids as active modulators of excitatory synaptic transmission.

查看原文本刊更多论文

溶血磷脂酸选择性调节海马神经元的兴奋性传递。

背景：溶血磷脂酸（LPA）是一种影响海马兴奋性突触传递的生物活性磷脂。结果：本研究提供了LPA通过激活LPA2受体在原代培养的小鼠海马神经元中诱导细胞内钙浓度（[Ca2+]i）瞬态的体外证据。在下游，通过gi偶联，这导致磷脂酶C （PLC）激活，肌醇（1,4,5）三磷酸（IP3）诱导的Ca2+释放（IICR）和电压门控Ca2+通道激活。此外，我们发现LPA不仅在胞体而且在突触前终末升高[Ca2+]i。这改变了自发囊泡释放的频率，特别是在兴奋性突触中。然而，与我们的预期相反，LPA降低了微型兴奋性突触后电流的频率。这是由于可释放的囊泡由于缓慢的再循环而耗竭。基于synaptophorin的测量表明，释放短暂增加，随后是膜上囊泡的持续时间延长。与我们之前在离体脑切片上的发现一致，LPA增加了Banker型星形细胞共培养中自发的谷氨酸能囊泡释放。我们的研究结果表明，促兴奋性LPA效应严重依赖于稳定的囊泡池。结论：综上所述，我们的数据进一步支持膜源磷脂作为兴奋性突触传递的主动调节剂。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Cell and Bioscience BIOCHEMISTRY & MOLECULAR BIOLOGY-

CiteScore

10.70

自引率

0.00%

发文量

187

审稿时长

>12 weeks

期刊介绍： Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.