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Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex. Learn Mem 2010 Jun;17(6):289-96

Date

05/28/2010

Pubmed ID

20504949

Pubmed Central ID

PMC2884289

DOI

10.1101/lm.1597410

Scopus ID

2-s2.0-77953047945 (requires institutional sign-in at Scopus site)   137 Citations

Abstract

The contribution of the medial prefrontal cortex (mPFC) to the formation of memory is a subject of considerable recent interest. Notably, the mechanisms supporting memory acquisition in this structure are poorly understood. The mPFC has been implicated in the acquisition of trace fear conditioning, a task that requires the association of a conditional stimulus (CS) and an aversive unconditional stimulus (UCS) across a temporal gap. In both rat and human subjects, frontal regions show increased activity during the trace interval separating the CS and UCS. We investigated the contribution of prefrontal neural activity in the rat to the acquisition of trace fear conditioning using microinfusions of the gamma-aminobutyric acid type A (GABA(A)) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-d-aspartate (NMDA) receptor-mediated signaling in trace fear conditioning using the NMDA receptor antagonist 2-amino-5-phosphonovaleric acid (APV). Temporary inactivation of prefrontal activity with muscimol or blockade of NMDA receptor-dependent transmission in mPFC impaired the acquisition of trace, but not delay, conditional fear responses. Simultaneously acquired contextual fear responses were also impaired in drug-treated rats exposed to trace or delay, but not unpaired, training protocols. Our results support the idea that synaptic plasticity within the mPFC is critical for the long-term storage of memory in trace fear conditioning.

Author List

Gilmartin MR, Helmstetter FJ

Author

Fred Helmstetter PhD Professor in the Psychology / Neuroscience department at University of Wisconsin - Milwaukee




MESH terms used to index this publication - Major topics in bold

Animals
Conditioning, Classical
Fear
GABA Agonists
Male
Memory
Muscimol
Neuronal Plasticity
Prefrontal Cortex
Rats
Rats, Long-Evans
Receptors, N-Methyl-D-Aspartate
Synaptic Transmission
Valine