Changes in Synaptic Excitability in the Lateral Septum Associated with Contextual and Auditory Fear Conditioning in Mice

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Abstract
Synaptic excitability in the lateral septum (LS) was assessed electrophysiologically in freely moving mice either submitted to a painful stimulus (shock) or tested on two forms of conditioned fear: contextual conditioning and auditory cue conditioning. Only the amplitude of the N3 component of the two negative waves (N2 and N3) evoked by fimbrial stimulation displayed significant changes in these tests. Experiment 1 showed that both the painful stimulus and subsequent re-exposure (24 h later) to the conditioning foreground context induced significant and context specific decrease in the N3 amplitude. In Experiment 2, a phasic tone (conditioned stimulus: CS) was paired (paired group) with the footshock (unconditioned stimulus: US) or not (unpaired group) and, 24 h later, animals were re-exposed successively to the auditory cue and to the context. During the auditory cue test, only the paired group displayed significant freezing and this occurred only during presentation of the CS. In this group, however, a significant reduction in the N3 amplitude was only observed immediately after the cessation of the CS. During the context test, the percentage and time-course of freezing across the 10 mm session were similar in each group. However, in the unpaired group the N3 amplitude reduction was significant and outlasted the duration of the freezing behaviour itself. These results show that alterations in LS synaptic excitability may be dissociated from fear-induced freezing behaviour. We suggest that LS synapses are part of a brain circuit that predict if and when the US is going to occur.