Dissociating retrieval-dependent contextual aversive memory processes in female rats: Are there cycle-dependent differences?

Retrieval-Dependent Mechanisms Affecting Emotional Memory Persistence: Reconsolidation, Extinction, and the Space in Between

“…It has been observed for discrete auditory fear memories in rats, where bidirectional manipulations of NMDAR activity affected memory reconsolidation or extinction when administered before brief or prolonged CS re-exposure sessions respectively (Lee et al, 2006a ), but no effect when administered before an intermediate number of CSs (Merlo et al, 2014 ). Similar results were observed for the pavlovian conditioned approach (Flavell and Lee, 2013 ) and contextual fear memories in rats (Cassini et al, 2017 ; Franzen et al, 2019 ), and fear memories in humans and crabs (Sevenster et al, 2014 ; Merlo et al, 2019 ), suggesting that “limbo” is an evolutionarily conserved feature in retrieval-dependent associative memory processing.…”

“…During limbo, the memory is not only insensitive to NMDAR manipulations. Administration of midazolam, an enhancer of GABAergic activity, also failed to affect contextual fear conditioned responding after intermediate CS re-exposure (Alfei et al, 2015 ; Franzen et al, 2019 ). Furthermore, protein synthesis inhibition, a “gold standard” amnestic manipulation, did not affect conditioned responding when administered after an intermediate number of CS re-exposures in the crab Neohelice granulatus (Merlo et al, 2019 ).…”

Identification of a Novel Retrieval-dependent Memory Process in the Crab Neohelice granulata

“…In auditory fear conditioned rats intermediate CS exposures engage a novel retrieval-dependent process which we have called 'limbo', characterised by insensitivity of the CS-US memory to amnestic treatments and a lack of extinction-specific molecular correlates (Merlo, Milton, and Everitt, 2018;Merlo, Milton, Goozee, Theobald, and Everitt, 2014). Limbo has also been documented for Pavlovian-conditioned contextual fear, and appetitive memories in rats (Cassini, Flavell, Amaral, and Lee, 2017;Flavell and Lee, 2013;Franzen, Giachero, and Bertoglio, 2019), as well as conditioned fear in humans (Kindt, Soeter, and Sevenster, 2014).…”

Limited replicability of drug-induced amnesia after contextual fear memory retrieval in rats

“…Details of the intervention, such as duration of the reactivation session and drug dose, are indicated as well. Franzen et al (2019) found no amnestic effect during initial testing after MDZ injection following a longer (5-min) re-exposure session, but the effect was only apparent after a 'reinstatement' procedure. The numbers in the second column refer to the lab of the corresponding author: In a series of 25 conceptual replication attempts, we varied properties of the training and reactivation session and used several amnestic drugs (MDZ, PROP, and/or cycloheximide) and doses.…”

“…First, MDZ (1.5 or 3 mg/kg) was administered 20 min before contextual fear conditioning, resulting in lower locomotor activity during the 3-min pre-shock period of the training session, and lower fear memory expression during the retention test (compared to SAL). Second, MDZ was administered after extinction, in line with prior publications showing that MDZ can interfere with extinction consolidation (Alfei et al, 2015;Bustos et al, 2009;Ferrer Monti et al, 2017;Franzen, Giachero, & Bertoglio, 2019). We adopted training parameters from Alfei et al (2015) and Ferrer Monti et al 2017and administered MDZ (or SAL) after a 30-min re-exposure session, but did not replicate their results, suggesting that MDZ did not affect extinction consolidation.…”