Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the trauma and by a memory impairment that decreases the ability to restrict fear to the appropriate context. Infusion of glucocorticoids in the hippocampus after fear conditioning induces PTSD-like memory impairments and an altered pattern of neural activation in the hippocampal-amygdalar circuit. Mice become unable to identify the context as the correct predictor of the threat and show fear responses to a discrete cue not predicting the threat in normal conditions. These data demonstrate PTSD-like memory impairments in rodents and identify a potential pathophysiological mechanism of this condition.

Convergent data suggest dissociated roles for the lateral (LA) and basolateral (BLA) amygdaloid nuclei in fear conditioning, depending on whether a discrete conditioned stimulus (CS)-unconditional stimulus (US) or context-US association is considered. Here, we show that pretraining inactivation of the BLA selectively impaired conditioning to context. In contrast, inactivation of the LA disrupted conditioning to the discrete tone CS, but also either impaired or enhanced contextual conditioning, depending on whether the context was in the foreground or in the background. Hence, these findings refine the current model of the amygdala function in emotional learning by showing that the BLA and the LA not only differentially contribute to elemental and context-US association, but also promote, through their interaction, the most relevant of these two associations.

Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is thought to play a critical role in the coordination between different memory systems leading to the selection of appropriate behavioral strategies, we hypothesized that this cholinergic signal may control the competing acquisition of amygdala-mediated tone and contextual conditioning. Using pavlovian fear conditioning in mice, we first show a higher level of hippocampal acetylcholine release and a specific pattern of extracellular signalregulated kinase 1/2 (ERK1/2) activation within the lateral (LA) and basolateral (BLA) amygdala under conditions in which the context is a better predictor than a discrete tone stimulus. Second, we demonstrate that levels of hippocampal cholinergic neurotransmission are causally related to the patterns of ERK1/2 activation in amygdala nuclei and actually determine the selection among the context or the simple tone the stimulus that best predicts the aversive event. Specifically, decreasing the hippocampal cholinergic signal not only impaired contextual conditioning but also mimicked conditioning to the discrete tone, both in terms of the behavioral outcome and the LA/BLA ERK1/2 activation pattern. Conversely, increasing this cholinergic signal not only disrupted tone conditioning but also promoted contextual fear conditioning. Hence, these findings highlight that hippocampal cholinergic neurotransmission controls amygdala function, thereby leading to the selection of relevant emotional information.

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.Extensive evidence has implicated the septum in fear and anxiety. On the one hand, previous studies have shown that damage to the septum could result in anxiolytic-like behavioral effects McNaughton 1983, 2000). In this context, Gray (1982) proposed a model according to which activity of the septalhippocampal complex reflects a state of "anxiety" produced when there is a mismatch between predicted and actual sensory events. By preventing animals from detecting such a change, lesions or inactivation of the septum would then cause a decrease in fear or anxiety. On the other hand, septal lesions were also found to profoundly increase fear and anxiety-related behaviors (Thomas 1988), producing the "septal rage syndrome" in many species (Brady and Nauta 1953). This syndrome would result from a generalized disinhibition of fear leading to exacerbated defensive reactions. Hence, a long history of lesion studies indicates that the septum plays a predominant role in fear learning, yet the direction of this control is still a matter of debate.The septal complex is anatomically heterogeneous. While the lateral septum (LS) receives a massive glutamatergic fiber input from the hippocampus by the fornix pathway, the medial septum (MS) sends impressive cholinergic and GABAergic projections to the hippocampus (Jakab and Leranth 1995; Swanson and Risold 2000).Functionally, the MS has been shown to be critically involved in regulating some physiologica...

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In several mammalian species, prenatal exposure to odours can elicit later positive consummatory behaviour in response to substrates bearing that odorant. In birds, the sense of smell has been considerably underestimated, and very little is known about the effects of early sensory experience on the regulation of feeding behaviour. We tested the hypothesis that the feeding behaviour of the domestic chicken could be regulated by olfactory learning during the embryonic life. To that end, chicken embryos were exposed to an olfactory stimulus (blend of essential oil of orange and nature identical vanillin) from embryonic day (ED) 12 to ED20, and chicks were tested between 4 and 9 d of age. In short‐term choice tests, at day 4 and 5, chickens previously exposed to a low concentration (LC) of the olfactory stimulus spent a higher proportion of time eating a familiar or an unfamiliar food bearing the olfactory stimulus compared to non‐exposed control chickens. Conversely, chickens previously exposed to a high concentration (HC) of the olfactory stimulus were found to avoid all foods bearing the olfactory stimulus. On a 24‐ h time scale at day 7–8, LC and HC birds, but not controls, ingest significantly less familiar food containing the olfactory stimulus. This result indicated a long‐term effect of the early olfactory experience on feeding preferences. We demonstrated that chickens can utilize information from their pre‐hatch chemosensory environment to guide their later feeding behaviour. A pre‐hatch effect of the intensity of odour signals in the regulation of feeding behaviour is reported here for the first time.

Previous studies using neuronal cell adhesion molecule (NCAM) −/− knockout (KO) mice provided evidence for a role of NCAMs in social behaviors. However, polysialic acid (PSA), the most important post-translational modification of NCAM, was also absent in these mice, which makes it difficult to distinguish between the specific involvement of either PSA or NCAM in social interactions. To address this issue, we assessed two lines of mice deficient for one of the two sialyltransferase enzymes required for the polysialylation of NCAM, sialyltransferase-X (St8SiaII or STX) and polysialyltransferase (ST8SiaIV or PST), in a series of tests for social behaviors. Results showed that PST KO mice display a decreased motivation in social interaction. This deficit can be partly explained by olfactory deficits and was associated with a clear decrease in PSA-NCAM expression in all brain regions analyzed (amygdala, septum, bed nucleus of the stria terminalis and frontal cortices). STX KO mice displayed both a decreased social motivation and an increased aggressive behavior that cannot be explained by olfactory deficits. This finding might be related to the reduced anxiety-like behavior, increased locomotion and stress-induced corticosterone secretion observed in these mice. Moreover, STX KO mice showed mild increase of PSA-NCAM expression in the lateral septum and the orbitofrontal cortex. Altogether, these findings support a role for PSA-NCAM in the regulation of social behaviors ranging from a lack of social motivation to aggression. They also underscore STX KO mice as an interesting animal model that combines a behavioral profile of violence and hyperactivity with reduced anxiety-like behavior.