Search bioRxiv⌕ Search

Biology subjects

Amorim, F. E.

Publications and source records attributed to Amorim, F. E..

6 recordsLinked to original sources

The silence of the rewards: Non-reward cue suppresses cue-driven behaviour in pavlovian-instrumental transfer

Flexible reward-seeking relies upon an organisms integration of expectations about environmental cues with knowledge of actions that produce rewards, which is captured by pavlovian instrumental transfer (PIT). Although widely used to study motivation across species, rodent PIT paradigms differ from human tasks in lacking an active baseline for comparison. Here we adapted the full PIT paradigm to include a non-rewarded cue (CSO) as an active control with the aim of improving the translational relevance of the procedure. Despite robust pavlovian and instrumental learning, neither male nor female rats expressed outcome-specific PIT when the active baseline was present. The absence of PIT persisted even after instrumental extinction training prior to the test, though cue-driven magazine approaches remained elevated. Data obtained under these conditions may reflect protocol-dependent modulation by the amount of training, or strain-specific differences in motivational influence. Replicated across male and female cohorts, they identify boundary conditions where PIT appears less robust. This methodological adaptation advances the translational alignment between animal and human PIT paradigms and informs future investigations into the mechanisms of cue-motivated behaviour.

animal behavior and cognition↗

Dopamine Dynamics in the Nucleus Accumbens Reflect Confidence in Detecting the Occurrence and Non-Occurrence of Visual Signals in Perceptual Decision-Making

Dopamine (DA) is critically involved in processes such as reward anticipation, attention, and decision - making. The present study examined the temporal dynamics of phasic DA transients in the nucleus accumbens core (NAcC) during a visual decisional task based on signal detection theory, using the fluorescent DA sensor dLight1.3b. During the decision-making phase, DA transients in the NAcC encoded real-time outcome expectancy, apparently reflecting the confidence of rats in their choices. Reward prediction errors (RPEs) emerged following reward delivery and omission and were amplified under conditions of increased uncertainty, produced either by degrading the visual target or introducing interfering distraction. Moreover, DA transients were elicited on both visual signal and no-signal trials. These findings demonstrate that DA fluctuations in the NAcC reflect the RPE that incorporates confidence and levels of uncertainty, emphasizing an involvement of nucleus accumbens DA in adaptive decision-making.

neuroscience↗

A meta-analysis of the effect of protein synthesis inhibitors on rodent fear conditioning

Systematic reviews and meta-analyses have been increasingly recognized for their potential value in pre-clinical research, but their applications have not been extensively explored in behavioral neuroscience. In this work, we studied protein synthesis inhibition, a classic intervention used to disrupt fear learning, reconsolidation, and extinction in rodents, to explore how meta-analyses can identify potential moderators of its effect. We initially performed separate meta-analyses for different injection sites and target sessions to evaluate the effect of the intervention in various scenarios. Heterogeneity was further investigated by multilevel meta-regression models aggregating various sites, with article or research group as additional levels. We detected robust effects of protein synthesis inhibitors on training and reconsolidation, but not on extinction, possibly due to the lower number of studies on the latter. Our analyses identified some well-established moderators, such as intervention timing and reexposure duration. However, other factors proposed as boundary conditions for reconsolidation, such as memory age and training strength, were not associated with effect size. While our results point to the value of meta-analyses in consolidating findings from the literature, we believe that associations suggested by data synthesis should ideally be verified by well-powered, rigorous confirmatory experiments.

neuroscience↗

Memory destabilization during reconsolidation - A consequence of homeostatic plasticity?

Remembering is not a static process: when retrieved, a memory can be destabilized and become prone to modifications. This phenomenon has been demonstrated in a number of brain regions, but the neuronal mechanisms that rule memory destabilization and its boundary conditions remain elusive. Using two distinct computational models that combine Hebbian plasticity and synaptic downscaling, we show that homeostatic plasticity can function as a destabilization mechanism, accounting for behavioral results of protein synthesis inhibition upon reactivation with different reexposure times. Furthermore, by performing systematic reviews, we identify a series of overlapping molecular mechanisms between memory destabilization and synaptic downscaling, although direct experimental links between both phenomena remain scarce. In light of these results, we propose a theoretical framework where memory destabilization can emerge as an epiphenomenon of homeostatic adaptations prompted by memory retrieval.

neuroscience↗

Shifting from fear to safety through deconditioning-update: a novel approach to attenuate fear memories

Aversive memories are at the heart of psychiatric disorders such as phobias and post-traumatic stress disorder (PTSD). Here, we present a new behavioral approach in rats that robustly attenuates aversive memories. This method consists of \"deconditioning\" animals previously trained to associate a tone with a strong footshock by replacing it with a much weaker one during memory retrieval. Our results indicate that deconditioning-update is more effective than traditional extinction in reducing fear responses; moreover, such effects are long lasting and resistant to renewal and spontaneous recovery. Remarkably, this strategy overcame important boundary conditions for memory updating, such as remote or very strong traumatic memories. The same beneficial effect was found in other types of fear-related memories. Deconditioning was mediated by L-type voltage-gated calcium channels and is consistent with computational accounts of mismatch-induced memory updating. Our results suggest that shifting from fear to safety through deconditioning-update is a promising approach to attenuate traumatic memories.

neuroscience↗

Different temporal windows for contextual fear memory destabilisation in the amygdala and hippocampus

Reconsolidation is a process in which re-exposure to a reminder causes a previously acquired memory to undergo a process of destabilisation followed by subsequent restabilisation. Different molecular mechanisms have been postulated for destabilisation in the amygdala and hippocampus, including CB1 receptor activation, protein degradation and AMPA receptor exchange; however, most of the amygdala studies have used pre-re-exposure interventions, while those in the hippocampus have performed them after re-exposure. To test whether the temporal window for destabilisation is similar across both structures, we trained Lister Hooded rats in a contextual fear conditioning task, and 1 day later performed memory re-exposure followed by injection of either the NMDA antagonist MK-801 (0.1 mg/kg) or saline in order to block reconsolidation. In parallel, we also performed local injections of either the CB1 antagonist SR141716A or its vehicle in the hippocampus or in the amygdala, either immediately before or immediately after reactivation. Infusion of SR141716A in the hippocampus prevented the reconsolidation-blocking effect of MK-801 when performed after re-exposure, but not before it. In the amygdala, meanwhile, pre-reexposure infusions of SR141716A impaired reconsolidation blockade by MK-801, although the time-dependency of this effect was not as clear as in the hippocampus. Our results suggest the temporal windows for CB1-receptor-mediated memory destabilisation during reconsolidation vary between brain structures. Whether this reflects different time windows for engagement of these structures or different roles played by CB1 receptors in destabilisation across structures remains an open question for future studies.

neuroscience↗