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

Abstract

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.

Infralimbic cortex controls fear memory generalization and susceptibility to extinction during consolidation

“…Most aspects mentioned in this section were conducted as fully described elsewhere 20 , 29 , 30 . Briefly, contextual fear conditioning was performed in a rectangular chamber (35 × 20 × 30 cm), with aluminum sidewalls and a front wall and ceiling-door made of Plexiglas, designated herein as context A.…”

“…Most aspects mentioned in this section were conducted as fully described elsewhere 20 , 29 , 30 . Briefly, at the end of the experiments, animals were anesthetized as already described for surgery, received a lethal dose of chloral hydrate (3.0 ml/kg of a 15% solution).…”

“…contextual fear conditioning and elevated plus-maze apparatuses, behavioral procedures, and data collection. Most aspects mentioned in this section were conducted as fully described elsewhere 20,29,30 .…”

Effects of ∆9-tetrahydrocannabinol on aversive memories and anxiety: a review from human studies

“…Besides, the relative contribution of a given brain region in each case may vary. For instance, the rodent prelimbic cortex (dACC in humans) is more involved in aversive memory reconsolidation than extinction [11,[25][26][27]. The age and intensity of the memory are factors that influence the chance of destabilization upon retrieval in both laboratory and clinical settings [28][29][30][31].…”

Prelimbic proBDNF facilitates memory destabilization by regulation of neuronal function in juveniles

“…These opposing fear-related behaviors depend on distinct components of a medial prefrontal cortical circuit that receive projections from the amygdala and ventral hippocampus (Milad and Quirk, 2002; Sotres-Bayon et al , 2012). Further researches indicate that the developmental changes in the extinction and recall of cued fear memories involve protracted development of prelimbic region of medial prefrontal cortex (mPFC) (Da Silva et al , 2020; Kim et al , 2009). Importantly, the prelimbic subregion of mPFC remains immature after birth and develops, undergoing a process of programmed synaptic pruning followed by regulation of synaptic and neuronal function which can persist into adulthood and continue organization of maturation circuitry (Burgos-Robles et al , 2009; Sotres-Bayon et al , 2012).…”