Dorsal hippocampus NMDA receptors differentially mediate trace and contextual fear conditioning

Abstract

The dorsal hippocampus (DH) is critically involved in the acquisition and expression of trace and contextual fear conditioning. NMDA/glutamate receptor-mediated transmission is thought to be one mechanism mediating the plastic changes that support long-term memories in the DH. However, their precise involvement in acquisition and expression processes has not been defined. To examine this issue, the NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid (APV; 10 microg/microl; 0.5 microl), was infused into the DH prior to conditioning and/or testing, using a trace fear conditioning procedure. All rats were tested for freezing to both tone and context in separate, counterbalanced sessions. The three sessions (1 training and 2 test) were separated by approximately 24 h. Using this design, it was possible to assess the role for DH NMDA receptors in the acquisition versus expression of trace and contextual fear conditioning. APV disrupted acquisition, but not expression, of contextual fear conditioning. By contrast, APV attenuated both acquisition and expression of trace fear memories. Thus, DH NMDA receptors appear to contribute to retrieval of some, but not all, fear memories.

Nicotine withdrawal disrupts both foreground and background contextual fear conditioning but not pre-pulse inhibition of the acoustic startle response in C57BL/6 mice

“…For instance, contextual fear conditioning may depend more on the dorsal hippocampus than the ventral hippocampus [3,54,67]. In support, Lee and Kesner [49] demonstrated that all three subregions of the dorsal hippocampus (CA3, CA1, and dentate gyrus) contribute to the acquisition of contextual memory.…”

“…Although fear conditioning and PPI both depend upon the hippocampus [3,36,49,54,67,85], each task may differentially recruit subregions of the hippocampus [3,36,43,49,54,67,85]. For instance, contextual fear conditioning may depend more on the dorsal hippocampus than the ventral hippocampus [3,54,67].…”

“…Like fear conditioning, PPI is dependent on the hippocampus [3,36,49,54,67,85] and thus may serve as a control for general deficits in hippocampal function during nicotine withdrawal. PPI is a phenomenon in which a low threshold initial stimulus, called a pre-pulse, suppresses subsequent responding to a startling stimulus [40] and is used as a measure of sensory gating [2,23,79].…”

Role of a Hippocampal Src-Family Kinase-Mediated Glutamatergic Mechanism in Drug Context-Induced Cocaine Seeking

“…For instance, NMDAR stimulation is necessary for the retrieval or expression of spatial, inhibitory avoidance, and trace fear memory (Corcoran et al, 2011;Matus-Amat et al, 2007;Melik et al, 2006;Quinn et al, 2005;Rodrigues et al, 2001), but not contextual fear memory (Fellini et Pound sign represents significant difference relative to all other time points (ANOVA time simple main effect, Tukey test, po0.05). Yoshihara and Ichitani, 2004).…”

Genetic variability in nicotinic acetylcholine receptors and nicotine addiction: Converging evidence from human and animal research

“…Mice acquire a context-US and a CS-US association, but the insertion of a time interval between the CS and US requires working memory to be engaged [15]. Therefore, the hippocampus is required for both the context-US and CS-US associations [114,134]. Research from our lab has demonstrated that β2 KO mice show no enhancement of trace cued conditioning by acute nicotine, whereas WT littermates do [34].…”