Pedreira, M. E. | bioRxiv Science

bioRxiv2020

A working memory intervention weakens the reconsolidation of a threat memory and its biases processing towards threat.

BACKGROUNDThreat-conditioning (TC) memory plays a central role in anxiety disorders, but not in a simple way. This memory impacts on complex cognitive systems by modifying behavioral responses with a bias to fearful stimuli and overestimating potential threats. In this study we proposed a global approach analyzing the scope of disrupting TC memory reconsolidation in the implicit memory, the declarative contingency and the cognitive biases. METHODSDay 1: Subjects were trained on TC. Day 2: after Threat-memory reactivation, one group performed a high demanding working memory task (HWM) and the other a low demanding working memory task (LWM). The last group, only performed the HWM task. Day 3: TC memory was tested by an extinction session followed by reinstatement. Finally, all subjects completed tasks targeting stimuli representation, valuation and attentional bias towards threat. RESULTSDisrupting reconsolidation of TC memory with a HWM weakened the implicit memory retention and faded the representation and valuation towards threat but it had no effect on attentional bias. Moreover, we revealed that subjects performance during the working memory task was specifically associated in TC memory retention. CONCLUSIONSOur findings reveal a strong impairment of the threat-memory restabilization and associated emotional biases. This may result from the competition between defensive survival and central-executive control networks. Our results fits with Experimental Psychopathology approach, disentangling the relation between the implicit memory, cognitive, valenced systems and the possibility to weaken both the threatening memory and the systems associated with the maintenance of anxiety profile.

neuroscience↗

bioRxiv2019

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

Fully consolidated associative memories may be altered by alternative retrieval dependent memory processes. While a brief exposure to the conditioned stimulus (CS) can trigger reconsolidation of the original memory, a prolonged CS exposure will trigger memory extinction. The conditioned response is maintained after reconsolidation, but is inhibited after extinction, presumably by the formation of a new inhibitory memory trace. In rats and humans, it has been shown that CS exposure of intermediate duration leave the memory in an insensitive or limbo state. Limbo is characterised by the absence of reconsolidation or extinction. Here we investigated the evolutionary conserved nature of limbo using a contextual Pavlovian conditioning (CPC) memory paradigm in the crab Neohelice granulata. In animals with fully consolidated CPC memory, systemic administration of the protein synthesis inhibitor cycloheximide after 1 CS presentation disrupted the memory, presumably by interfering with memory reconsolidation. The same intervention given after 320 CSs prevented CPC memory extinction. Cycloheximide had no behavioural effect when administered after 80 CS presentations, a protocol that failed to extinguish CPC memory. Also, we observed that a stronger CPC memory engaged reconsolidation after 80 CS instead of limbo, indicating that memory strength affects the parametrical conditions to engage either reconsolidation or limbo. Altogether, these results indicate that limbo is an evolutionary conserved memory process segregating reconsolidation from extinction in the number of CSs space. Limbo appears as an intrinsic component of retrieval dependent memory processing, with a key function in the transition from memory maintenance to inhibition. Author statement (CRediT Roles)Santiago A. Merlo: Conceptualization, Data curation, Formal Analysis, Investigation, Software, Validation, Visualization, Writing - original draft, Writing - review & editing. Jimena Santos: Investigation, Writing - review & editing. Maria Eugenia Pedreira: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing. Emiliano Merlo: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Validation, Writing - original draft, Writing - review & editing.

neuroscience↗