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Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction.
Behav Brain Res. 2014 Feb 01; 259:45-9.BB

Abstract

Although fear extinction requires N-methyl-d-aspartate (NMDA) receptor signaling, Cav2.1-regulated synaptic function in extinction remains unknown. This study examined whether Cav2.1-mediated signaling plays role in consolidation of extinction. Wild-type mice received intracerebroventricular injection of Cav2.1 blocker (ω-agatoxin IVA, 4.0 pg/side) showed impaired extinction behavior and increased expression of CREB-dependent gene Arc in medial prefrontal cortex (mPFC). Intra-mPFC injections of NMDA receptor antagonist (MK-801, 0.5 μg/midline), which was ineffective in wild-type controls, blocked extinction in heterozygous rolling Nagoya (rol/+) mice carrying Cav2.1α1 gene mutation rol/+ mice. These results indicate that Cav2.1-mediated NMDA receptor signaling is functional pathway in mPFC-dependent fear extinction. Our results also indicate that the combination of pharmacological and genetic approaches can be used to study functional signaling pathways in neuronal circuits.

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Publisher Full Text (DOI)

Authors+Show Affiliations

Niimi K
Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Han Y
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China.
Zhou Y
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China.
Yoshimoto T
Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
Dai F
Hefei First People's Hospital, Huaihe Road 390, Hefei 230061, PR China.
Teng X
Department of Endocrinology and Metabolism, The First Affiliated Hospital, China Medical University, Shenyang, Liaoning 110001, PR China.
Tian X
Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095-1690, USA.
Li W
Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: liwd@sjtu.edu.cn.
Takahashi E
Research Resources Center, RIKEN Brain Science Institute, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200240, PR China. Electronic address: etakahashi@brain.riken.jp.

MeSH

Analysis of VarianceAnimalsCalcium Channel BlockersCalcium Channels, N-TypeConditioning, PsychologicalDizocilpine MaleateDose-Response Relationship, DrugExcitatory Amino Acid AntagonistsExtinction, PsychologicalFearMiceMice, Inbred C57BLPrefrontal CortexReceptors, N-Methyl-D-AspartateSignal TransductionTime Factorsomega-Agatoxin IVA

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24177210

Citation

Niimi, Kimie, et al. "Blockade of Cav2.1-mediated NMDA Receptor Signaling Disrupts Conditioned Fear Extinction." Behavioural Brain Research, vol. 259, 2014, pp. 45-9.
Niimi K, Han Y, Zhou Y, et al. Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction. Behav Brain Res. 2014;259:45-9.
Niimi, K., Han, Y., Zhou, Y., Yoshimoto, T., Dai, F., Teng, X., Tian, X., Li, W., & Takahashi, E. (2014). Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction. Behavioural Brain Research, 259, 45-9. https://doi.org/10.1016/j.bbr.2013.10.033
Niimi K, et al. Blockade of Cav2.1-mediated NMDA Receptor Signaling Disrupts Conditioned Fear Extinction. Behav Brain Res. 2014 Feb 1;259:45-9. PubMed PMID: 24177210.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction. AU - Niimi,Kimie, AU - Han,Yanfei, AU - Zhou,Ying, AU - Yoshimoto,Takuro, AU - Dai,Fu, AU - Teng,Xiaochun, AU - Tian,Xiaoli, AU - Li,Weidong, AU - Takahashi,Eiki, Y1 - 2013/10/28/ PY - 2013/09/11/received PY - 2013/10/17/revised PY - 2013/10/20/accepted PY - 2013/11/2/entrez PY - 2013/11/2/pubmed PY - 2014/8/5/medline KW - Cav2.1 KW - Fear extinction KW - Neuronal circuits KW - Rolling Nagoya mice KW - ω-Agatoxin IVA SP - 45 EP - 9 JF - Behavioural brain research JO - Behav Brain Res VL - 259 N2 - Although fear extinction requires N-methyl-d-aspartate (NMDA) receptor signaling, Cav2.1-regulated synaptic function in extinction remains unknown. This study examined whether Cav2.1-mediated signaling plays role in consolidation of extinction. Wild-type mice received intracerebroventricular injection of Cav2.1 blocker (ω-agatoxin IVA, 4.0 pg/side) showed impaired extinction behavior and increased expression of CREB-dependent gene Arc in medial prefrontal cortex (mPFC). Intra-mPFC injections of NMDA receptor antagonist (MK-801, 0.5 μg/midline), which was ineffective in wild-type controls, blocked extinction in heterozygous rolling Nagoya (rol/+) mice carrying Cav2.1α1 gene mutation rol/+ mice. These results indicate that Cav2.1-mediated NMDA receptor signaling is functional pathway in mPFC-dependent fear extinction. Our results also indicate that the combination of pharmacological and genetic approaches can be used to study functional signaling pathways in neuronal circuits. SN - 1872-7549 UR - https://www.unboundmedicine.com/medline/citation/24177210/Blockade_of_Cav2_1_mediated_NMDA_receptor_signaling_disrupts_conditioned_fear_extinction_ DB - PRIME DP - Unbound Medicine ER -