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

Behavioural brain research 2014 Feb 1

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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. Copyright © 2013 Elsevier B.V. All rights reserved.

Citation

Kimie Niimi, Yanfei Han, Ying Zhou, Takuro Yoshimoto, Fu Dai, Xiaochun Teng, Xiaoli Tian, Weidong Li, Eiki Takahashi. Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction. Behavioural brain research. 2014 Feb 1;259:45-9