Dissociated roles for the lateral and medial septum in elemental and contextual fear conditioning.

L. Calandreau, R. Jaffard, A. Desmedt
Learning & Memory. 2007-06-06; 14(6): 422-429
DOI: 10.1101/lm.531407

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Extensive evidence indicates that the septum plays a predominant role in fear
learning, yet the direction of this control is still a matter of debate.
Increasing data suggest that the medial (MS) and lateral septum (LS) would be
differentially required in fear conditioning depending on whether a discrete
conditional stimulus (CS) predicts, or not, the occurrence of an aversive
unconditional stimulus (US). Here, using a tone CS-US pairing (predictive
discrete CS, context in background) or unpairing (context in foreground)
conditioning procedure, we show, in mice, that pretraining inactivation of the LS
totally disrupted tone fear conditioning, which, otherwise, was spared by
inactivation of the MS. Inactivating the LS also reduced foreground contextual
fear conditioning, while sparing the higher level of conditioned freezing to the
foreground (CS-US unpairing) than to the background context (CS-US pairing). In
contrast, inactivation of the MS totally abolished this training-dependent level
of contextual freezing. Interestingly, inactivation of the MS enhanced background
contextual conditioning under the pairing condition, whereas it reduced
foreground contextual conditioning under the unpairing condition. Hence, the
present findings reveal a functional dissociation between the LS and the MS in
Pavlovian fear conditioning depending on the predictive value of the discrete CS.
While the requirement of the LS is crucial for the appropriate processing of the
tone CS-US association, the MS is crucial for an appropriate processing of
contextual cues as foreground or background information.

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