Newly acquired and reactivated contextual fear memories are more intense and prone to generalize after activation of prelimbic cortex NMDA receptors

Vanvossen, Ana Carolina; Portes, Marina A.M.; Scoz-Silva, Rafael; Reichmann, Hugo B.; Stern, Cristina Aparecida Jark; Bertoglio, Leandro J.

doi:10.1016/j.nlm.2016.12.002

Cited by 31 publications

(20 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The working hypothesis was that the outcome would qualitatively differ from that previously reported, being influenced by the inactivation approach selectivity and duration. Of note, as shown by our research group and others, often the greater the number of shocks delivered the more intense the contextual fear memory generated (Baldi, Lorenzini, & Bucherelli, ; Gazarini, Stern, Carobrez, & Bertoglio, ; Stern et al, ; Vanvossen et al, ). If so, the possible NR inactivation‐induced increase in freezing during re‐exposure to the conditioning context, could be masked due to a higher basal level of this behavior presented by the controls.…”

Section: Introductionsupporting

confidence: 67%

“…A more generalized aversive memory has been shown to be less prone to decay over time (Migues et al, ). Since increased persistence was in turn associated with reduced behavioral and plastic flexibility (Richards & Frankland, ), and muscimol‐induced NR inactivation was able to impair behavioral flexibility in rats (Viena et al, ), a plausible explanation for our results is that inactivating the NR generates more intense aversive memories, which are often reported to be longer lasting and generalized (Heyman, ; Pitman, ; Gazarini et al, ; Vanvossen et al, ).…”

Section: Discussionmentioning

confidence: 66%

See 1 more Smart Citation

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation

2018

Self Cite

View full text Add to dashboard Cite

The thalamic nucleus reuniens (NR) has been shown to support bidirectional medial prefrontal cortex-hippocampus communication and synchronization relevant for cognitive processing. Using non-selective or prolonged inactivation of the NR, previous studies reported its activity positively modulates aversive memory consolidation. Here we examined the NR's role in consolidating contextual fear memories with varied strength, at both recent and more remote time points, using muscimol-induced temporary inactivation in rats. Results indicate the NR negatively modulates fear memory intensity, specificity, and long-term maintenance. The more intense, generalized, and enduring fear memory induced by NR inactivation during consolidation was less prone to behavioral suppression by extinction or reconsolidation disruption induced by clonidine, an alpha-2 adrenergic receptor agonist. Lastly, we used immunohistochemistry for Arc protein, which is involved in synaptic modifications underlying memory consolidation, to investigate whether treatment condition and/or conditioning status could change its levels not only in the NR, but also in the hippocampus (dorsal and ventral CA1 subregions) and the medial prefrontal cortex (anterior cingulate, prelimbic and infralimbic subregions). Results indicate a significant imbalance in the number of Arc-expressing neurons in the brain areas investigated in muscimol fear conditioned animals when compared with controls. Collectively, present results provide convergent evidence for the NR's role as a hub regulating quantitative and qualitative aspects of a contextual fear memory during its consolidation that seem to influence the subsequent susceptibility to experimental interventions aiming at attenuating its expression. They also indicate the selectivity and duration of a given inactivation approach may influence its outcomes.

show abstract

Section: Introductionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 66%

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation

2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…This is of interest since it may possibly suggest that DCS can facilitate generalization of the learning to other stimuli than the CS+ which was initially associated with the US. Generalization of learning effects after administration of DCS was found in previous studies (Byrne et al 2015;Ledgerwood et al 2005;Vanvossen et al 2017). In Fig.…”

Section: Discussionsupporting

confidence: 71%

“…It was found that there was no difference between conditions with the new stimulus in the treatment context, in contrast to the alternate context, where participants in the DCS condition showed less avoidance and less fear towards the new stimulus compared to participants in the placebo condition. In addition, Vanvossen et al (2017) observed that in rats, activation of prelimbic cortex NMDA receptors after acquisition of a contextual fear memory resulted in enhanced fear expression to another context, indicating generalized fear expression through enhanced fear memory consolidation. Ledgerwood et al (2005) state that their results may point to DCS reducing stimulus specificity, since extinction training with one CS rarely results in a loss in responding to a different CS previously paired with the same US.…”

Section: Discussionmentioning

confidence: 99%

A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on sexual memory consolidation in women

et al. 2020

View full text Add to dashboard Cite

Rationale and objective The aim of this study was to investigate the possible facilitating effect of the partial NMDA receptor agonist D-cycloserine (DCS) on memory consolidation of conditioned sexual responses and to examine the capability of DCS to reduce context-specificity of learning. Methods In a randomized placebo-controlled double-blind trial, 50 healthy females were exposed to a differential conditioning procedure. Two pictures of a male abdomen were used as conditional stimuli (CSs), of which one (the CS+) was followed by the unconditional stimulus (US), a genital vibrotactile stimulus. After the conditioning session on day 1, participants received either 125 mg of DCS or a placebo. The effects of DCS on affect, sexual arousal and US expectancy in response to the CS+ and CS− were examined 24 h after the conditioning procedure.Results A main effect of DCS was found on affect at the first test trials (p = 0.04, η p 2 = 0.09), and a similar non-significant but trend level effect was found for sexual arousal (p = 0.06, η p 2 = 0.07), which appeared to persist over a longer time (p = 0.07, η p 2 = 0.08). Unexpectedly, ratings of positive affect and sexual arousal in response to both the CS+ and the CS− were higher in the DCS condition compared to the control condition, possibly indicating that DCS administration reduced stimulus specificity. Since the results did not show clear evidence for context learning, we were not able to test effects on context-specificity of learning. Conclusion Although largely inconclusive, the results provide tentative support for a facilitating effect of DCS on affect and sexual arousal in response to stimuli that were presented in a sexual conditioning procedure, however, no conclusions can be drawn about effects of DCS on sexual reward learning, since the design and results do not lend themselves to unambiguous interpretation.

show abstract

“…The PL cortex has been implicated in aversive memory reconsolidation 20,21 . PKMζ expression in this medial prefrontal cortex sub-region also seems to support the maintenance of newly acquired aversive memories 22 .…”

mentioning

confidence: 99%

Role of prelimbic cortex PKC and PKMζ in fear memory reconsolidation and persistence following reactivation

Silva

Raymundi

Bertoglio

et al. 2020

Sci Rep

View full text Add to dashboard Cite

the persistence of newly acquired memories is supported by the activity of pKMζ, an atypical isoform of protein kinase c (pKc). Whether the activity of conventional and atypical pKc isoforms contributes to reactivated memories to persist is still unknown. Similarly, whether memory reactivation is a prerequisite for interventions to be able to change memory persistence is scarcely investigated. Based on the above, we examined the role of conventional and atypical pKc isoforms in the prelimbic cortex in reconsolidation and persistence of a reactivated contextual fear memory in male Wistar rats. it is shown that (i) inhibiting the pKc activity with chelerythrine or the pKMζ activity with Zip impaired the persistence of a reactivated memory for at least 21 days; (ii) ZIP given immediately after memory reactivation affected neither the reconsolidation nor the persistence process. In contrast, when given 1 h later, it impaired the memory persistence; (iii) chelerythrine given immediately after memory reactivation impaired the reconsolidation; (iv) omitting memory reactivation prevented the chelerythrine-and ZIP-induced effects: (v) the ZIP action is independent of the time elapsed between its administration and the initial memory test. the results indicate that prelimbic cortex pKc and pKMζ are involved in memory reconsolidation and persistence.

show abstract

Newly acquired and reactivated contextual fear memories are more intense and prone to generalize after activation of prelimbic cortex NMDA receptors

Cited by 31 publications

References 58 publications

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation

Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation

A randomized, placebo-controlled laboratory study of the effects of D-cycloserine on sexual memory consolidation in women

Role of prelimbic cortex PKC and PKMζ in fear memory reconsolidation and persistence following reactivation

Contact Info

Product

Resources

About