Role of TRPC6 in conditioning and extinction of contextual fear memory in mice

Yiqin TIAN; Xiuxiu CHEN; Chen BIAN; Min LI

doi:10.16016/j.1000-5404.201909229

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Role of TRPC6 in conditioning and extinction of contextual fear memory in mice

Clinical Medicine | 更新时间：2026-01-09

- Role of TRPC6 in conditioning and extinction of contextual fear memory in mice
- Journal of Third Military Medical University Vol. 42, Issue 5, Pages: 533-538(2020)
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)医学心理系：军事心理学教研室
  2.400038 重庆，陆军军医大学(第三军医大学)医学心理系：军人发展心理学教研室
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(31500896);the Program of Natural Science Foundation of Chongqing(CSTC2016jcyjA0587);the Project of Military Medical Advanced Research(2016XYY06);the Key Project of Youth Innovation Fund of Faculty of Medical Psychology of Army Medical University(KY2018101)
- DOI：10.16016/j.1000-5404.201909229
  CLC： R329.27;R338.64;R395.1
- Received：30 September 2019，
  
  Revised：2019-12-18，
  
  Published：15 March 2020
- 稿件说明：
移动端阅览
Yiqin TIAN, Xiuxiu CHEN, Chen BIAN, et al. Role of TRPC6 in conditioning and extinction of contextual fear memory in mice[J]. Journal of Third Military Medical University, 2020, 42(5): 533-538.
DOI：

Yiqin TIAN, Xiuxiu CHEN, Chen BIAN, et al. Role of TRPC6 in conditioning and extinction of contextual fear memory in mice[J]. Journal of Third Military Medical University, 2020, 42(5): 533-538. DOI： 10.16016/j.1000-5404.201909229.

摘要

目的

探讨瞬时受体电位阳离子通道6(transient receptor potential canonical 6，TRPC6)在情景性条件恐惧记忆建立和消退中的作用。

方法

取6~8周龄雄性成年C57BL/6J小鼠32只，采用随机数字表法分为条件恐惧对照组(

=8)、条件恐惧干扰组(

=8)、恐惧消退对照组(

=8)和恐惧消退干扰组(

=8)。干扰组双侧海马注射携带TRPC6干扰RNA的腺相关病毒，对照组双侧海马注射等量空病毒。于注射后20 d采用免疫荧光和Western blot检测小鼠海马TRPC6的表达。恐惧记忆建立实验:于病毒注射后21 d进行情景性条件恐惧的建立(由5次0.7 mA、2 s、间隔58 s不可逃避的足底电击组成)，22 d进行恐惧记忆测试；恐惧消退实验:于注射后4 d进行情景条件恐惧的建立，21 d进行消退训练，22 d进行消退记忆测试。

结果

病毒注射后20 d，小鼠海马CA1区锥体细胞层均可见大量GFP阳性表达细胞，Western blot结果显示:病毒干扰组海马TRPC6的表达显著低于空病毒对照组(

0.01)。在恐惧记忆建立实验中，条件恐惧干扰组的僵直行为百分比上升趋势较条件恐惧对照组显著减慢(

0.05)，24 h后的恐惧记忆检测中，条件恐惧干扰组的僵直行为百分比也显著低于条件恐惧对照组(

0.05)。在情景恐惧记忆消退实验中，恐惧消退干扰组的僵直行为百分比下降趋势较恐惧消退对照组显著减慢(

0.05)，24 h后的消退记忆检测中恐惧消退干扰组的僵直行为百分比也显著高于恐惧消退对照组(

0.05)。

结论

海马TRPC6参与情景恐惧记忆的形成和消退过程，抑制海马TRPC6的表达会破坏恐惧记忆的形成和消退。

Abstract

Objective

To explore the role of transient receptor potential canonical 6 (TRPC6) on conditioning and extinction in contextual fear memory.

Methods

A total of 32 male C57BL/6J mice (6~8 weeks old) were randomized into fear conditioning (Cond group

=16) and fear extinction (Ext group

=16). Both groups were further divided into sh-TRPC6 subgroup (

=8) and GFP subgroup (

=8). Stereotaxic injection of adeno-associated virus (AAV)-TRPC6 or AAV-green fluorescent protein (AAV-GFP) was performed into the hippocampus of the corresponding mice bilaterally for intervention of fear. Immunofluorescence assay and Western blotting were used to detect the expression of TRPC6 in hippocampus of each sub-group in 20 d after stereotaxic injection. On day 21

fear conditioning was established though inescapable foot shock (footshock of 0.7 mA for 2 s and intertrial interval for 58 s

totally 5 cycles)

and fear test was carried out on day 22. For the mice from the Ext group

fear conditioning begun in 4 d after stereotaxic injection

fear extinction training started on day 21

and fear test was also carried out on day 22.

Results

At 20 d after injection

massive GFP-positive cells were observed in the pyramidal layer of hippocampal CA1 region

and Western blotting showed AAV-TRPC6 injection significantly reduced the hippocampal TRPC6 expression in the sh-TRPC6 subgroup than the GFP subgroup (

0.01). In the experiment of fear conditioning

the upward trend of the Freezing% levels in sh-TRPC6 subgroup was obviously slower (

0.05)

and its Freezing% levels were notably lower in fear test when compared with the GFP subgroup (

0.05). In the experiment of fear extinction

the downward trend of the Freezing% levels in sh-TRPC6 subgroup was significantly slower (

0.05)

and its Freezing% levels were significantly higher in fear test when compared with the GFP subgroup (

0.05).

Conclusion

Hippocampal TRPC6 participates in the conditioning and extinction in contextual fear memory

and suppression of its expression can destroy the processes.

关键词

Keywords

references

YEHUDA R, HOGE C W, MCFARLANE A C, et al . Post-traumatic stress disorder[J ] . Nat Rev Dis Primers, 2015, 1: 15057. DOI:10.1038/nrdp.2015.57.

DUNSMOOR J E, MURTY V P, DAVACHI L, et al . Emotional learning selectively and retroactively strengthens memories for related events[J ] . Nature, 2015, 520(7547): 345-348. DOI:10.1038/nature14106.

MAREN S, PHAN K L, LIBERZON I. The contextual brain: implications for fear conditioning, extinction and psychopathology[J]. Nat Rev Neurosci, 2013, 14(6): 417-428. DOI:10.1038/nrn3492.

BENDER C L, GIACHERO M, COMAS-MUTIS R, et al . Stress influences the dynamics of hippocampal structural remodeling associated with fear memory extinction[J ] . Neurobiol Learn Mem, 2018, 155: 412-421. DOI:10.1016/j.nlm.2018.09.002.

LAI C S W, ADLER A, GAN W B. Fear extinction reverses dendritic spine formation induced by fear conditioning in the mouse auditory cortex[J]. Proc Natl Acad Sci USA, 2018, 115(37): 9306-9311. DOI:10.1073/pnas.1801504115.

REBOREDA A, THEISSEN F M, VALERO-ARACAMA M J, et al . Do TRPC channels support working memory? Compar ing modulations of TRPC channels and working memory through G-protein coupled receptors and neuromodulators[J ] . Behav Brain Res, 2018, 354: 64-83. DOI:10.1016/j.bbr.2018.02.042.

NEUNER S M, WILMOTT L A, HOPE K A, et al . TRPC3 channels critically regulate hippocampal excitability and contextual fear memory[J ] . Behav Brain Res, 2015, 281: 69-77. DOI:10.1016/j.bbr.2014.12.018.

ZHOU J, DU W L, ZHOU K C, et al . Critical role of TRPC6 channels in the formation of excitatory synapses[J ] . Nat Neurosci, 2008, 11(7): 741-743. DOI:10.1038/nn.2127.

HAIT N C, WISE L E, ALLEGOOD J C, et al . Active, phosphorylated fingolimod inhibits histone deacetylases and facilitates fear extinction memory[J ] . Nat Neurosci, 2014, 17(7): 971-980. DOI:10.1038/nn.3728.

NAGAYOSHI T, ISODA K, MAMIYA N, et al . Hippocampal calpain is required for the consolidation and reconsolidation but not extinction of contextual fear memory[J ] . Mol Brain, 2017, 10(1): 61. DOI:10.1186/s13041-017-0341-8.

SOTRES-BAYON F, BUSH D E, LEDOUX J E. Acquisition of fear extinction requires activation of NR2B-containing NMDA receptors in the lateral amygdala[J]. Neuropsychopharmacology, 2007, 32(9): 1929-1940. DOI:10.1038/sj.npp.1301316.

MILAD M R, QUIRK G J. Fear extinction as a model for translational neuroscience: ten years of progress[J]. Annu Rev Psychol, 2012, 63: 129-151. DOI:10.1146/annurev.psych.121208.131631.

LACAGNINA A F, BROCKWAY E T, CROVETTI C R, et al . Distinct hippocampal engrams control extinction and relapse of fear memory[J ] . Nat Neurosci, 2019, 22(5): 753-761. DOI:10.1038/s41593-019-0361-z.

PAULA-LIMA A C, ADASME T, HIDALGO C. Contribution of Ca 2+ release channels to hippocampal synaptic plasticity and spatial memory: potential redox modulation[J ] . Antioxid Redox Signal, 2014, 21(6): 892-914. DOI:10.1089/ars.2013.5796.

崔龙彪, 金晓航, 史娟.中枢神经系统内的TRPC6离子通道[J].神经解剖学杂志, 2011, 27(5): 565-570.

CUI L B, JIN X H, SHI J. TRPC6 channels in the central nervous system[J]. Chin J Neuroanat, 2011, 27(5): 565-570.

MONTECINOS-OLIVA C, SCHULLER A, PARODI J, et al . Effects of tetrahydrohyperforin in mouse hippocampal sli ces: neuroprotection, long-term potentiation and TRPC channels[J ] . Curr Med Chem, 2014, 21(30): 3494-3506. DOI:10.2174/0929867321666140716091229.

LEUNER K, LI W, AMARAL M D, et al . Hyperforin modulates dendritic spine morphology in hippocampal pyramidal neurons by activating Ca 2+ -permeable TRPC6 channels[J ] . Hippocampus, 2013, 23(1): 40-52. DOI:10.1002/hipo.22052..

HEISER J H, SCHUWALD A M, SILLANI G, et al . TRPC6 channel-mediated neurite outgrowth in PC12 cells and hippocampal neurons involves activation of RAS/MEK/ERK, PI3K, and CAMKIV signaling[J ] . J Neurochem, 2013, 127(3): 303-313. DOI:10.1111/jnc.12376.

TAI Y L, FENG S J, GE R L, et al . TRPC6 channels promote dendritic growth via the CaMKIV-CREB pathway[J ] . J Cell Sci, 2008, 121(Pt 14): 2301-2307. DOI:10.1242/jcs.026906..

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