The Posterior Insular Cortex is Necessary for the Consolidation of Tone Fear Conditioning

Paiva, de; Buéno,; ecirca, dos Santos Corr; Oliveira, Maria Gabriela Menezes; Ferreira, J.A.M.; Fornari, Raquel Vecchio

doi:10.1101/2020.08.12.248294

Cited by 4 publications

(4 citation statements)

References 55 publications

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“…It seems likely to be. The engagement of the aIC in the retrieval of CFC is intensity-dependent, as its post-training functional inhibition impairs recent retrieval after stronger trainings (Alves et al, 2013) but not weaker ones (de Paiva et al, 2021). This dependence on the training intensity was also reported in the PrL in mice (Matos et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

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

Corrêa

Grisanti

Franciscatto

et al. 2021

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Corrêa

Grisanti

Franciscatto

et al. 2021

Preprint

Self Cite

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“…Behavioral experiments were conducted in two identical automated fear conditioning chambers (Med-Associates, Inc., St. Albans, VT) connected to a computer interface enabling video recording, analysis and automated measurement of the rat’s freezing behavior in real time. The chambers and software used were previously described in detail (de Paiva et al, 2021; dos Santos Corrêa et al, 2019). Freezing measure was automated (VideoFreeze Version 1.12.0.0, MedAssociates) and set for less than 20 movement units for at least 30 frames (1s) (Bueno et al, 2017; Moreira-Silva et al, 2018).…”

Section: Methodsmentioning

confidence: 99%

Corticosterone differentially modulates time-dependent fear generalization following mild or moderate fear conditioning training in rats

Correa

Vaz

Menezes

et al. 2021

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Stressful and emotionally arousing experiences create strong memories that seem to lose specificity over time. It is uncertain, however, how the stress system contributes to the phenomenon of time-dependent fear generalization. Here, we investigated whether the glucocorticoid hormonal system affects the specificity of contextual fear memories at several timepoints. We trained male Wistar rats on the contextual fear conditioning (CFC) task using two footshock intensities (mild CFC, 3 footshocks of 0.3 mA, or moderate CFC, 3x 0.6 mA) and immediately after the training session we administered corticosterone (CORT-HBC) systemically. We first tested the animals in a novel context and then in the training context at different intervals following training (2, 14, 28 or 42 days). By measuring freezing in the novel context and then contrasting freezing times shown in both contexts, we inferred contextual fear generalization for each rat, classifying them into Generalizers or Discriminators. Following mild CFC training, the glucocorticoid induced an increased discriminative contextual memory that lasted from two up to 28 days. In contrast, after moderate CFC training, CORT-HBC facilitated contextual generalization at 14 days, compared to the control group that maintained contextual discrimination at this timepoint. For this training intensity, however, CORT-HBC did not have any effect on recent memory specificity. These findings indicate that manipulating glucocorticoid levels after mild or moderately arousing experiences may differentially modulate memory consolidation and time-dependent fear generalization.

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“…An earlier lesion study in rats has found evidence for a role of the pInsCx in fear learning (Shi and Davis, 1999), while others have not (Brunzell and Kim, 2001; Lanuza et al, 2004). More recent studies using pharmacological inactivation have described roles of the pInsCx in safety learning (Foilb et al, 2016), and in fear memory consolidation (Casanova et al, 2016; de Paiva et al, 2021). Also, the notion of a pInsCx to LA connection has not been confirmed in recent anatomical studies in mice, which found outputs from the pInsCx to the central amygdala (CeA), but only weak ones to the LA (Gehrlach et al, 2019; Gehrlach et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

An insular cortex to lateral amygdala pathway in fear learning

Palchaudhuri

Osypenko

Kochubey

et al. 2023

Preprint

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During fear learning, associations between an aversive stimulus (the US), and a sensory cue (CS) are formed at specific brain synapses. Nevertheless, how US information is transmitted to brain areas involved in value processing, like the amygdala, is still elusive. Using optogenetics, in-vivo Ca2+imaging, and circuit tracing, we investigate the role of the posterior insular cortex (pInsCx) and relevant output pathways of this cortical area in fear learning. Optogenetic suppression of US-signaling in pInsCx principal neurons compromises auditory-cued fear learning. The pInsCx makes a robust glutamatergic synapse in the lateral amygdala (LA), which undergoes long-term potentiation after fear learning, and transmits US-information to a sub-population of LA neurons. Suppressing US-signaling in LA-projectors recapitulates the fear learning deficits observed after silencing pInsCx principal neurons. Thus, the pInsCx, via a plastic output synapse, transmits US-information to the LA and critically contributes to the formation of auditory-cued fear memories.

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The Posterior Insular Cortex is Necessary for the Consolidation of Tone Fear Conditioning

Cited by 4 publications

References 55 publications

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

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

Corticosterone differentially modulates time-dependent fear generalization following mild or moderate fear conditioning training in rats

An insular cortex to lateral amygdala pathway in fear learning

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