RRC ID 27919
Author Niimi K, Han Y, Zhou Y, Yoshimoto T, Dai F, Teng X, Tian X, Li W, Takahashi E.
Title Blockade of Cav2.1-mediated NMDA receptor signaling disrupts conditioned fear extinction.
Journal Behav. Brain Res.
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.
Volume 259
Pages 45-9
Published 2014-2-1
DOI 10.1016/j.bbr.2013.10.033
PII S0166-4328(13)00648-7
PMID 24177210
MeSH Analysis of Variance Animals Calcium Channel Blockers / pharmacology Calcium Channels, N-Type / metabolism* Conditioning (Psychology) / drug effects Conditioning (Psychology) / physiology* Dizocilpine Maleate / pharmacology Dose-Response Relationship, Drug Excitatory Amino Acid Antagonists / pharmacology Extinction, Psychological / drug effects Fear / drug effects Fear / physiology* Mice Mice, Inbred C57BL Prefrontal Cortex / drug effects Prefrontal Cortex / metabolism Receptors, N-Methyl-D-Aspartate / metabolism* Signal Transduction / drug effects Signal Transduction / physiology Time Factors omega-Agatoxin IVA / pharmacology
IF 2.77
Times Cited 2
Mice PROD-rol/+(RBRC00388)