Referenced in: none

Automatically associated channels: Cav2.1

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

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

Journal, date & volume: Behav. Brain Res., 2014 Feb 1 , 259, 45-9

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24177210

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.