Contextual Conditioned Fear Blocks the Induction But Not the Maintenance of Lateral Septal LTP in Behaving Mice

1997 ◽  
Vol 78 (1) ◽  
pp. 76-81 ◽  
Author(s):  
René Garcia ◽  
Rose Marie Vouimba ◽  
Robert Jaffard

Garcia, René, Rose Marie Vouimba, and Robert Jaffard. Contextual conditioned fear blocks the induction but not the maintenance of lateral septal LTP in behaving mice. J. Neurophysiol. 78: 76–81, 1997. High-frequency stimulation (HFS) of the fimbria induces long-term potentiation (LTP) in the lateral septum. This study was aimed at investigating the effect of contextual fear conditioning on septal LTP with the use of behaving C57 BL/6 mice as subjects. For the acquisition of contextual fear conditioning, animals were placed in a conditioning chamber, where they were subjected to footshocks (FSs, 0.6 mA); the following day (retention), animals were reexposed to the chamber. Animals from the first group received HFS in their home cages before being submitted to conditioning; animals from the second group were first submitted to conditioning before receiving HFS during reexposure to the conditioning chamber; animals from the third group were submitted to the same regimen as those from the second group, except that no FS was delivered in the conditioning chamber; and animals from the fourth group received FS in the conditioning chamber but were maintained in their home cages the day after for LTP induction. Before conditioning, animals from the first group, placed in a familiar context (home cage), displayed an LTP of the N3 wave of septal field potential. After conditioning, reexposure of these animals to the conditioning chamber produced a transient decrease in the amplitude of N3 but did not interfere with the duration of maintenance of LTP. Conversely, in animals from the second group, when HFS was applied during reexposure to the conditioning chamber the induction of LTP was totally blocked. However, mice from the two other groups (3rd and 4th) displayed normal levels of LTP. Taken together with previous findings, these data suggest that contextual conditioned fear may interfere with certain forms of learning via blockade of hippocampal-septal LTP.

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 193 ◽  
Author(s):  
Ivar S. Stein ◽  
Michaela S. Donaldson ◽  
Johannes W. Hell

Learning and memory as well as long-term potentiation (LTP) depend on Ca2+ influx through the NMDA-type glutamate receptor (NMDAR) and the resulting activation of the Ca2+ and calmodulin-dependent protein kinase (CaMKII). Ca2+ influx via the NMDAR triggers CaMKII binding to the NMDAR for enhanced CaMKII accumulation at post-synaptic sites that experience heightened activity as occurring during LTP. Previously, we generated knock-in (KI) mice in which we replaced two residues in the NMDAR GluN2B subunit to impair CaMKII binding to GluN2B. Various forms of LTP at the Schaffer collateral synapses in CA1 are reduced by 50%. Nevertheless, working memory in the win-shift 8 arm maze and learning of the Morris water maze (MWM) task was normal in the KI mice although recall of the task was impaired in these mice during the period of early memory consolidation. We now show that massed training in the MWM task within a single day resulted in impaired learning. However, learning and recall of the Barnes maze task and contextual fear conditioning over one or multiple days were surprisingly unaffected. The differences observed in the MWM compared to the Barnes maze and contextual fear conditioning suggest a differential involvement of CaMKII and the specific interaction with GluN2B, probably depending on varying degrees of stress, cognitive demand or even potentially different plasticity mechanisms associated with the diverse tasks.


10.1038/nn791 ◽  
2002 ◽  
Vol 5 (2) ◽  
pp. 155-161 ◽  
Author(s):  
Jonathan Levenson ◽  
Edwin Weeber ◽  
Joel C. Selcher ◽  
Lorna S. Kategaya ◽  
J. David Sweatt ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Katy L. H. Marshall-Phelps ◽  
Gernot Riedel ◽  
Peer Wulff ◽  
Marta Woloszynowska-Fraser

AbstractPurkinje cells are the only output cell of the cerebellar cortex. Their spatiotemporal activity is controlled by molecular layer interneurons (MLIs) through GABAA receptor-mediated inhibition. Recently, it has been reported that the cerebellar cortex is required for consolidation of conditioned fear responses during fear memory formation. Although the relevance of MLIs during fear memory formation is currently not known, it has been shown that synapses made between MLIs and Purkinje cells exhibit long term plasticity following fear conditioning. The present study examined the role of cerebellar MLIs in the formation of fear memory using a genetically-altered mouse line (PC-∆γ2) in which GABAA receptor-mediated signaling at MLI to Purkinje cell synapses was functionally removed. We found that neither acquisition nor recall of fear memories to tone and context were altered after removal of MLI-mediated inhibition.


2002 ◽  
Vol 9 (4) ◽  
pp. 233-247 ◽  
Author(s):  
R. C. B. Silva ◽  
A. P. M. Cruz ◽  
V. Avanzi ◽  
J. Landeira-Fernandez ◽  
M. L. Brandão

Ascending 5-HT projections from the median raphe nucleus (MRN), probably to the hippocampus, are implicated in the acquisition of contextual fear (background stimuli), as assessed by freezing behavior. Foreground cues like light, used as a conditioned stimulus (CS) in classical fear conditioning, also cause freezing through thalamic transmission to the amygdala. As the MRN projects to the hippocampus and amygdala, the role of this raphe nucleus in fear conditioning to explicit cues remains to be explained. Here we analyzed the behavior of rats with MRN electrolytic lesions in a contextual conditioning situation and in a fear-potentiated startle procedure. The animals received MRN electrolytic lesions either before or on the day after two consecutive training sessions in which they were submitted to 10 conditioning trials, each in an experimental chamber (same context) where they. received foot-shocks (0.6 mA, 1 sec) paired to a 4-sec light CS. Seven to ten days later, the animals were submitted to testing sessions for assessing conditioned fear when they were placed for five shocks, and the duration of contextual freezing was recorded. The animals were then submitted to a fear-potentiated startle in response to a 4-sec light-CS, followed by white noise (100 dB, 50 ms). Control rats (sham) tested in the same context showed more freezing than did rats with pre- or post-training MRN lesions. Startle was clearly potentiated in the presence of light CS in the sham-lesioned animals. Whereas pretraining lesions reduced both freezing and fear-potentiated startle, the post-training lesions reduced only freezing to context, without changing the fear-potentiated startle. In a second experiment, neurotoxic lesions of the MRN with local injections of N-methyl-D-aspartate or the activation of5-HT1Asomatodendritic auto-receptors of the MRN by microinjections of the5-HT1Areceptor agonist 8-hydroxy- 2-(di-n-propylamino)tetralin (8-OH-DPAT) before the training sessions also reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in posttraining lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN.


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