An 8-day extensive elemental, but not contextual, fear conditioning potentiates hippocampal-lateral septal synaptic efficacy in mice.

Previous findings have suggested a critical role for hippocampal-lateral septal (HPC-LS) synaptic transmission in the modulation of elemental vs. contextual fear conditioning. Pharmacologically- or electrophysiologically-induced increases in HPC-LS neurotransmission were shown to be associated with both an increase in elemental and a decrease in contextual fear conditioning. However, elemental conditioning, induced by an unconditional stimulus (US) that was explicitly paired with a simple conditional stimulus (CS), did not result in any change in this neurotransmission when two tone CS-footshock US pairings were provided. The present experiment was thus designed to investigate directly, in mice, whether extensive elemental conditioning (repeated CS-US pairings) could induce an increase in HPC-LS neurotransmission. For that purpose, over 8 days, an elemental conditioning group was repeatedly submitted to CS-US pairings in either one context (A) or another (B) depending on the training day. Hence, whichever the context, the tone CS was the relevant predictive stimulus for the occurrence of the footshock US. In contrast, a contextual conditioning group was submitted to the same regimen except that the US was delivered only in context A and was never paired with the CS, making, thereby, the context A the relevant predictor for the US regardless of the occurrence of the tone CS. Results show that during re-exposure of the animals to either context A or B, a significant increase in HPC-LS neurotransmission was selectively associated with the repeated elemental conditioning. This study supports the idea that changes in HPC-LS neurotransmission may modulate the strength of simple CS-US associations, and suggests that alterations of hippocampal functioning might be involved.