scholarly journals Remote contextual fear retrieval engages activity from salience network regions in rats

2021 ◽  
Author(s):  
Moisés dos Santos Corrêa ◽  
Gabriel David Vieira Grisanti ◽  
Isabelle Anjos Fernandes Franciscatto ◽  
Tatiana Suemi Anglas Tarumoto ◽  
Paula Ayako Tiba ◽  
...  

The ability to retrieve contextual fear memories depends on the coordinated activation of a brain-wide circuitry. Transition from recent to remote memories seems to involve the reorganization of this circuitry, a process called systems consolidation that has been associated with time-dependent fear generalization. However, it is not known whether emotional memories acquired under different levels of stress can undergo different systems consolidation processes. Here, we explored the activation pattern and functional connectivity of key brain regions associated with contextual fear conditioning (CFC) retrieval after recent (2 days) or remote (28 days) memory tests performed in rats submitted to strong (1.0mA footshock) or mild (0.3mA footshock) training. We used brain tissue from Wistar rats from a previous study, where we observed that increasing training intensity promotes fear memory generalization over time, possibly due to an increase in corticosterone levels during memory consolidation. Analysis of Fos expression across 8 regions of interest (ROIs) allowed us to identify coactivation between them at both timepoints following memory recall. Our results showed that strong CFC elicits higher Fos activation in the anterior insular and prelimbic cortices during remote retrieval, which was - along with the basolateral amygdala - positively correlated with freezing. Rats trained either with mild or strong CFC showed a broad functional connectivity at the recent timepoint whereas only animals submitted to the strong CFC showed a widespread loss of coactivation during remote retrieval. Our findings suggest that increasing training intensity results in differential processes of systems consolidation, possibly associated with increased post-training corticosterone release, and that strong CFC engages activity from areas associated with the salience network during remote retrieval.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew R. Baker ◽  
Ryan Y. Wong

AbstractLearning to anticipate potentially dangerous contexts is an adaptive behavioral response to coping with stressors. An animal’s stress coping style (e.g. proactive–reactive axis) is known to influence how it encodes salient events. However, the neural and molecular mechanisms underlying these stress coping style differences in learning are unknown. Further, while a number of neuroplasticity-related genes have been associated with alternative stress coping styles, it is unclear if these genes may bias the development of conditioned behavioral responses to stressful stimuli, and if so, which brain regions are involved. Here, we trained adult zebrafish to associate a naturally aversive olfactory cue with a given context. Next, we investigated if expression of two neural plasticity and neurotransmission-related genes (npas4a and gabbr1a) were associated with the contextual fear conditioning differences between proactive and reactive stress coping styles. Reactive zebrafish developed a stronger conditioned fear response and showed significantly higher npas4a expression in the medial and lateral zones of the dorsal telencephalon (Dm, Dl), and the supracommissural nucleus of the ventral telencephalon (Vs). Our findings suggest that the expression of activity-dependent genes like npas4a may be differentially expressed across several interconnected forebrain regions in response to fearful stimuli and promote biases in fear learning among different stress coping styles.


2020 ◽  
Author(s):  
Ashley N Opalka ◽  
Dong V Wang

AbstractLearning and memory involves a large neural network of many brain regions, including the notable hippocampus along with the retrosplenial cortex (RSC) and lateral septum (LS). Previous studies have established that the dorsal hippocampus (dHPC) plays a critical role during the acquisition and expression of episodic memories. However, the role of downstream circuitry from the dHPC, including the dHPC-to-RSC and dHPC-to-LS pathways, has come under scrutiny only recently. Here, we employed an optogenetic approach with contextual fear conditioning in mice to determine whether the above two pathways are involved in acquisition and expression of contextual fear memory. We found that a selective inhibition of the dHPC neuronal terminals in either the RSC or LS during acquisition impaired subsequent memory performance, suggesting that both the dHPC-to-RSC and dHPC-to-LS pathways play a critical role in memory acquisition. We also selectively inhibited the two dHPC efferent pathways during memory expression and found a differential effect on memory performance. These results indicate the intricacies of memory processing and that hippocampal efferents to cortical and subcortical regions may be differentially involved in aspects of physiological and cognitive memory processes.


2021 ◽  
Author(s):  
Tanya Procyshyn ◽  
MIchael Lombardo ◽  
Meng-Chuan Lai ◽  
Bonnie Auyeung ◽  
Sarah Crockford ◽  
...  

Background: Oxytocin is hypothesized to promote positive social interactions by enhancing the salience of social stimuli, which may be reflected by altered amygdala activation. While previous neuroimaging studies have reported that oxytocin enhances amygdala activation to emotional face stimuli in autistic men, effects in autistic women remain unclear. Methods: The influence of intranasal oxytocin on neural response to emotional faces vs. shapes were tested in 16 autistic and 21 non-autistic women by fMRI in a placebo-controlled, within-subjects, cross-over design. Effects of group (autistic vs. non-autistic) and drug condition (oxytocin vs. placebo) on the activation and functional connectivity of the basolateral amygdala, the brain’s “salience detector”, were assessed. Relationships between individual differences in autistic-like traits, social anxiety, salivary oxytocin levels, and amygdala activation were also explored.Results: Autistic and non-autistic women showed minimal activation differences in the placebo condition. Significant drug × group interactions were observed for both amygdala activation and functional connectivity. Oxytocin increased left basolateral amygdala activation among autistic women (35 voxel cluster, MNI coordinates of peak voxel = -22 -10 -28; mean change=+0.079%, t=3.159, ptukey=0.0166), but not non-autistic women (mean change =+0.003%, t=0.153, ptukey=0.999). Furthermore, oxytocin increased functional connectivity of the right basolateral amygdala with brain regions associated with socio-emotional information processing in autistic women, but not non-autistic women, thereby attenuating group connectivity differences observed in the placebo condition. Conclusions: This work demonstrates that intranasal oxytocin increases basolateral amygdala activation and connectivity in autistic women while processing emotional faces, which extends and specifies previous findings in autistic men.


Author(s):  
Zeinab Khastkhodaei ◽  
Muthuraman Muthuraman ◽  
Jenq-Wei Yang ◽  
Sergiu Groppa ◽  
Heiko J. Luhmann

AbstractHigher cognitive processes and emotional regulation depend on densely interconnected telencephalic and limbic areas. Central structures of this cortico-limbic network are ventral hippocampus (vHC), medial prefrontal cortex (PFC), basolateral amygdala (BLA) and nucleus accumbens (NAC). Human and animal studies have revealed both anatomical and functional alterations in specific connections of this network in several psychiatric disorders. However, it is often not clear whether functional alterations within these densely interconnected brain areas are caused by modifications in the direct pathways, or alternatively through indirect interactions. We performed multi-site extracellular recordings of spontaneous activity in three different brain regions to study the functional connectivity in the BLA–NAC–PFC–vHC network of the lightly anesthetized mouse in vivo. We show that BLA, NAC, PFC and vHC are functionally connected in distinct frequency bands and determined the influence of a third brain region on this connectivity. In addition to describing mutual synchronicity, we determined the strength of functional connectivity for each region in the BLA–NAC–PFC–vHC network. We find a region-specificity in the strength of feedforward and feedback connections for each region in its interaction with other areas in the network. Our results provide insights into functional and directed connectivity in the cortico-limbic network of adult wild-type mice, which may be helpful to further elucidate the pathophysiological changes of this network in psychiatric disorders and to develop target-specific therapeutic interventions.


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