The Role of Serotonin in Fear Learning and Memory: A Systematic Review of Human Studies.

Fear is characterized by distinct behavioral and physiological responses that are essential for the survival of the human species. Fear conditioning (FC) serves as a valuable model for studying the acquisition, extinction, and expression of fear. The serotonin (5-hydroxytryptamine, 5-HT) system is known to play a significant role in emotional and motivational aspects of human behavior, including fear learning and expression. Accumulating evidence from both animal and human studies suggests that brain regions involved in FC, such as the amygdala, hippocampus, and prefrontal cortex, possess a high density of 5-HT receptors, implicating the crucial involvement of serotonin in aversive learning. Additionally, studies exploring serotonin gene polymorphisms have indicated their potential influence on FC. Therefore, the objective of this work was to review the existing evidence linking 5-HT with fear learning and memory in humans. Through a comprehensive screening of the PubMed and Web of Science databases, 29 relevant studies were included in the final review. These studies investigated the relationship between serotonin and fear learning using drug manipulations or by studying 5-HT-related gene polymorphisms. The results suggest that elevated levels of 5-HT enhance aversive learning, indicating that the modulation of serotonin 5-HT2A receptors regulates the expression of fear responses in humans. Understanding the role of this neurochemical messenger in associative aversive learning can provide insights into psychiatric disorders such as anxiety and post-traumatic stress disorder (PTSD), among others.

Memories are not written in stone: Re-writing fear memories by means of non-invasive brain stimulation and optogenetic manipulations.

The acquisition of fear associative memory requires brain processes of coordinated neural activity within the amygdala, prefrontal cortex (PFC), hippocampus, thalamus and brainstem. After fear consolidation, a suppression of fear memory in the absence of danger is crucial to permit adaptive coping behavior. Acquisition and maintenance of fear extinction critically depend on amygdala-PFC projections. The robust correspondence between the brain networks encompassed cortical and subcortical hubs involved into fear processing in humans and in other species underscores the potential utility of comparing the modulation of brain circuitry in humans and animals, as a crucial step to inform the comprehension of fear mechanisms and the development of treatments for fear-related disorders. The present review is aimed at providing a comprehensive description of the literature on recent clinical and experimental researches regarding the noninvasive brain stimulation and optogenetics. These innovative manipulations applied over specific hubs of fear matrix during fear acquisition, consolidation, reconsolidation and extinction allow an accurate characterization of specific brain circuits and their peculiar interaction within the specific fear processing.

State-Dependent TMS over Prefrontal Cortex Disrupts Fear-Memory Reconsolidation and Prevents the Return of Fear.

Erasing maladaptive memories has been a challenge for years. A way to change fear memories is to target the process of reconsolidation, during which a retrieved memory transiently returns to a labile state, amenable to modification [1, 2]. Disruption of human fear-memory reconsolidation has been classically attempted with pharmacological [3] or behavioral (e.g., extinction) [4] treatments that, however, do not clarify the underlying brain mechanism. To address this issue, in 84 healthy humans submitted to six experiments, here, we combined a differential fear conditioning paradigm with repetitive transcranial magnetic stimulation (rTMS) administered in a state-dependent manner. In a critical condition, we stimulated the dorsolateral prefrontal cortex (dlPFC) 10 min after a reminder cue that reactivated a fear memory acquired 1 day before. At testing, 24 h after rTMS, participants exhibited decreased physiological expression of fear, as shown by their skin conductance response. Similar reductions were observed when targeting the left and the right dlPFC. In contrast, no decrease was observed in participants tested immediately after dlPFC-rTMS or in participants receiving either control rTMS (i.e., active control site and sham stimulations) or dlPFC-rTMS without preceding fear-memory reactivation, thus showing both the site and time specificity and state dependency of our rTMS intervention. Expression of fear was indeed reduced only when dlPFC-rTMS was administered within the reconsolidation time window. Moreover, dlPFC-rTMS prevented subsequent return of fear after extinction training. These findings highlight the causal role of dlPFC in fear-memory reconsolidation and suggest that rTMS can be used in humans to prevent the return of fear.

Purification of residual leach liquors from hydrometallurgical process of NiMH spent batteries through micellar enhanced ultra filtration.

Hydrometallurgical processes for the treatment and recovery of metals from waste electrical and electronic equipment produce wastewaters containing heavy metals. These residual solutions cannot be discharged into the sewer without an appropriate treatment. Specific wastewater treatments integrated with the hydrometallurgical processes ensure a sustainable recycling loops of the electrical wastes to maximize the metals recovery and minimize the amount of wastes and wastewaters produced. In this research activity the efficiency of ultrafiltration combined with surfactant micelles (micellar-enhanced ultrafiltration) was tested to remove metals form leach liquors obtained after leaching of NiMH spent batteries. In the micellar-enhanced ultrafiltration, a surfactant is added into the aqueous stream containing contaminants or solute above its critical micelle concentration. When the surfactant concentration exceeding this critical value, the surfactant monomers will assemble and aggregate to form micelles having diameter larger than the pore diameter of ultrafiltration membrane. Micelles containing contaminants whose diameter is larger than membrane pore size will be rejected during ultrafiltration process, leaving only water, unsolubilized contaminants and surfactant monomers in permeate stream. The experiments are carried out in a lab-scale plant, where a tubular ceramic ultrafiltration membrane is used with adding a surfactant to concentrate heavy metals in the retentate stream, producing a permeate of purified water that can be reused inside the process, thus minimizing the fresh water consumption.

Treatment of WEEE industrial wastewaters: Removal of yttrium and zinc by means of micellar enhanced ultra filtration.

In this paper, the efficiency of micellar enhanced ultrafiltration technique (MEUF) was tested for the removal of yttrium and zinc ions from synthetic industrial liquid wastes. UF membranes (monotubular ceramic membranes of 210 kDa and 1 kDa molecular weight cut-off) were used with adding an anionic surfactant, sodium dodecyl sulfate (SDS). A two - level full factorial design was performed in order to evaluate the effect of molecular weight cut-off, sodium dodecyl sulfate concentration and pressure on the permeate flux and rejection yields. It was found that the single factors presented the largest influence on the permeate flux: the membrane pore size and the pressure had positive effect, instead the SDS had negative effect. Regarding the metal rejection yields the main relevant factors were the membrane pore size with a negative effect, followed by the surfactant concentration with a positive effect. The effect of the pressure seemed to be almost negligible, for zinc removal experiments had a positive effect in the interactions with the surfactant and membrane pore size. The results showed that very good removal percentages up to 99% were achieved for both metals under the following conditions: 1 kDa membrane MWCO, in the presence of the surfactant at a concentration above CMC independently of the investigated pressure.