Trace and contextual fear conditioning require neural activity and NMDA receptor-dependent transmission in the medial prefrontal cortex

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 g-aminobutyric acid type A (GABA A ) receptor agonist muscimol. We also investigated the role of prefrontal N-methyl-D-aspartate (NMDA) receptormediated 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.

Systemic Administration of γ-Hydroxybutyric Acid in Adolescent Rat Impairs Contextual Fear Conditioning, But Not Cued Conditioning

“…Alcohol has been reported to disrupt contextual freezing in young animals, and this alcohol-induced memory deficit is associated with significant CA1 pyramidal neuronal loss [6,35,59]. Some other brain areas that are thought to support contextual fear conditioning include parahippocampal structures [18,46], medial prefrontal cortex [20], medial geniculate nucleus [31], and cerebellum [48].…”

Effects of Elevation of Brain Magnesium on Fear Conditioning, Fear Extinction, and Synaptic Plasticity in the Infralimbic Prefrontal Cortex and Lateral Amygdala

“…1 E). Other studies show that other brain regions within the PFC, such as PrL-PFC (Gilmartin and Helmstetter, 2010) and/or anterior cingulate cortex (Han et al, 2003), also contribute to trace fear conditioning. Since MgT treatment enhanced NMDAR signaling in the PFC, it might have contributed to the improved ability to process temporal information in MgT-treated rats.…”

Activation of β2-adrenoceptor enhances synaptic potentiation and behavioral memory via cAMP-PKA signaling in the medial prefrontal cortex of rats

“…Post-training activation of b2-AR enhances trace fear memory in the mPFC Synaptic plasticity within the cortex is critical for trace fear memory (Gilmartin and Helmstetter 2010). LTP enhancement in layer 2/3 pyramidal cells of the cortex has been proposed to correspond with enhancement in trace fear conditioning (Wu et al 2008).…”

“…The PFC has been proposed to be involved in the acquisition and the storage of trace fear memory (Sacchetti et al 2002;Runyan et al 2004;Gilmartin and McEchron 2005). Synaptic plasticity within the mPFC is critical for the storage of trace fear memory (Gilmartin and Helmstetter 2010). However, the effect of mPFC noradrenergic modulation on trace fear memory remains unknown.…”