Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction

Kimie Niimi, Yanfei Han, Ying Zhou, Takuro Yoshimoto, Fu Dai, Xiaochun Teng, Xiaoli Tian, Weidong Li, Eiki Takahashi

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)45-49
Number of pages5
JournalBehavioural Brain Research
Volume259
DOIs
Publication statusPublished - Feb 1 2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Behavioral Neuroscience

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