Infralimbic cortex (IL) pyramidal neurons (PNs) have been implicated in suppressing instrumental cocaine seeking, yet their causal contribution to Pavlovian extinction and subsequent retrieval remains unclear. Using CaMKIIα promoter-driven chemogenetics, we bidirectionally modulated IL PN activity across extinction training, extinction expression, and primed reinstatement in a cocaine-conditioned place preference (CPP) paradigm in male mice. Manipulating IL PN activity during the extinction phase did not alter the progressive reduction of CPP across intermediate probe sessions, suggesting no effects on the formation of extinction. In contrast, acute inhibition of IL PNs impaired extinction expression, whereas stimulation did not further enhance performance, indicating that extinction retrieval is dependent on a sufficient level of IL PN activity that is likely achieved under baseline conditions. During cocaine-primed reinstatement, acute inhibition of IL PNs exacerbated the recovery of conditioned responses, while stimulation was critical to prevent reinstatement, suggesting that IL-mediated behavioral suppression is sensitive to the motivational state. Although coordinated activity in IL projection targets, including the nucleus accumbens shell, the basolateral and central amygdala, and the lateral entorhinal cortex, was observed during extinction expression and reinstatement, this activity did not explain additional variance beyond IL PN activity. Together, these findings highlight IL PNs as a central node in the expression of Pavlovian extinction and in shaping vulnerability to cocaine-induced relapse-like behavior.
Interest in the role of melanin-concentrating hormone (MCH) in memory processes has increased in recent years, with some studies reporting memory-enhancing effects, while others report deleterious effects. Due to these discrepancies, this study seeks to provide new evidence about the role of MCH in memory consolidation and its relation with BDNF/TrkB system. To this end, in the first experiment, increased doses of MCH were acutely administered in both hippocampi to groups of male rats (25, 50, 200, and 500 ng). Microinjections were carried out immediately after finishing the sample trial of two hippocampal-dependent behavioral tasks: the Novel Object Recognition Test (NORT) and the modified Elevated Plus Maze (mEPM) test. Results indicated that a dose of 200 ng of MCH or higher impaired memory consolidation in both tasks. A second experiment was performed in which a dose of 200 ng of MCH was administered alone or co-administered with the MCHR-1 antagonist ATC0175 at the end of the sample trial in the NORT. Results showed that MCH impaired memory consolidation, while the co-administration with ATC-0175 reverted this detrimental effect. Moreover, MCH induced a significant decrease in hippocampal MCHR-1 and TrkB expression with no modification in the expression of BDNF and NMDA receptor subunits NR1, NR2A, and NR2B. These results suggest that MCH in vivo elicits pro-amnesic effects in the rat hippocampus by decreasing the availability of its receptor and TrkB receptors, thus linking both endogenous systems to memory processes.
COPYRIGHT © 2023 Otero-Losada, Marseglia, Blanco Calvo and Capani. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Neurological comorbidity in metabolic syndrome
Coaching as a human development methodology has been demonstrating its results for more than four decades. Even so, the level of confusion about its essence and its lack of a definitive theoretical and methodological framework has caused its effectiveness to be questioned. Although studies on coaching with neuroimaging methodologies have been developed, there is no recent evidence about the brain changes in electroencephalographic (EEG) activity during a coaching session. The present research aims to make a comparison between EEG measurements of three different conditions, namely, rumination (R), directive (DC), and non-directive coaching (NDC), during the process of problem solving and goal achievement. Our hypothesis was that the use of the meta-competencies of NDC should induce a higher activation of brain mechanisms that facilitate the insight process, therefore causing an improvement in creative capacity. Results showed significant changes in alpha and theta frequencies in the right temporal region, and alpha, theta, and gamma in the right parietal region in the NDC condition compared to other experimental conditions. The correct use of the meta-competencies of NDC facilitates the rise of insight and the generation of creativity processes at the brain level. Thus, the application of the methodological framework of the NDC was related, in a specific way, to the creativity and the development of human knowledge.
COPYRIGHT © 2022 Luque-Rojas, Blanco Calvo and Martín-Aragoneses. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Editorial: Neuroscience, learning, and educational psychology
The Prefrontal cortex (PFC) has been highly related to executive functions such as working memory (WM). This study assesses the activity of the PFC in performing the Sternberg WM task (ST) with three levels of difficulty (easy, medium and hard) using the near-infrared spectroscopy (fNIRS) technique. Participants were 43 young and healthy right-handed women. Nine WM task blocks were pseudo randomly presented, three for each difficulty task. The results showed that the participant's performance was better in the easy trials than in the medium and hard trials. Performance in the medium trials was also better than in the hard ones. Bonferroni-corrected paired post-hoc t-tests indicated higher oxygenation in medium and hard tasks than in the easy ones for times between 13 and 42 s in the left lateral PFC and in both, medial and lateral, right PFC. Significant differences in Oxygenated hemoglobin (HbO), Total hemoglobin (HbT) and oxygenation (Oxy) changes depending on the Sternberg WM task were found. Unlike previous studies with fNIRS and WM, the current study uses a highly controlled WM task that differentiates between encoding, retention and retrieval phases, comparing different levels of task load.
The current research was designed to assess possible differences in the emotional content of pleasant and unpleasant face emoji using acoustically evoked eyeblink startle reflex response. Stimuli were selected from Emojipedia Webpage. First, we assessed these stimuli with a previous independent sample of 190 undergraduate students (46 males and 144 females) mean age of 21.43 years (SD 3.89). A principal axis method was performed using the 30 selected emoji faces, extracting two factors (15 pleasant and 15 unpleasant emoji). Second, we measured the acoustic startle reflex modulation in 53 young adult women [mean age 22.13 years (SD 4.3)] during the viewing of each of the 30 emoji emotional faces in the context of the theory of motivation and emotion proposed by Lang (1995), but considering only the valence dimension. We expected to find higher acoustically evoked startle responses when viewing unpleasant emoji and lower responses for pleasant ones, similarly to the results obtained in the studies using human faces as emotional stimulus. An ANOVA was conducted to compare acoustic startle responses associated with pleasant and unpleasant emoji. Results yielded main effects for picture valence (λ = 0.80, F(1, 50) = 12.80, p = .001, η2 = 0.20). Post-hoc t test analysis indicated significant differences in the startle response between unpleasant (50.95 ± 1.75) and pleasant (49.14 ± 2.49) emoji (t (52) = 3.59, p = .001), with a Cohen's d = 0.495. Viewing affective facial emoji expressions modulates the acoustic startle reflex response according to their emotional content.
Memory deficits affect a large proportion of the human population and are associated with aging and many neurologic, neurodegenerative, and psychiatric diseases. Treatment of this mental disorder has been disappointing because all potential candidates studied thus far have failed to produce consistent effects across various types of memory and have shown limited to no effects on memory deficits. Here, we show that the promotion of neuronal arborization through the expression of the regulator of G-protein signaling 14 of 414 amino acids (RGS14414) not only induced robust enhancement of multiple types of memory but was also sufficient for the recovery of recognition, spatial, and temporal memory, which are kinds of episodic memory that are primarily affected in patients or individuals with memory dysfunction. We observed that a surge in neuronal arborization was mediated by up-regulation of brain-derived neurotrophic factor (BDNF) signaling and that the deletion of BDNF abrogated both neuronal arborization activation and memory enhancement. The activation of BDNF-dependent neuronal arborization generated almost 2-fold increases in synapse numbers in dendrites of pyramidal neurons and in neurites of nonpyramidal neurons. This increase in synaptic connections might have evoked reorganization within neuronal circuits and eventually supported an increase in the activity of such circuits. Thus, in addition to showing the potential of RGS14414 for rescuing memory deficits, our results suggest that a boost in circuit activity could facilitate memory enhancement and the reversal of memory deficits.-Masmudi-Martín, M., Navarro-Lobato, I., López-Aranda, M. F., Delgado, G., Martín-Montañez, E., Quiros-Ortega, M. E., Carretero-Rey, M., Narváez, L., Garcia-Garrido, M. F., Posadas, S., López-Téllez, J. F., Blanco, E., Jiménez-Recuerda, I., Granados-Durán, P., Paez-Rueda, J., López, J. C., Khan, Z. U. RGS14414 treatment induces memory enhancement and rescues episodic memory deficits.
Neuroticism and Sensation Seeking are part of temperament that contribute to later personality. Both traits are related with internalizing and externalizing behavioral problems and psychiatric disorders. Neuroticism and Sensation Seeking are also associated with different genetic polymorphisms in several studies. In this research, we evaluated the involvement of 153 tagged single-nucleotide polymorphisms (tagSNPs) from 20 candidate-genes in a sample of 290 healthy Caucasian volunteers (147 males and 143 females). We explored the contribution of each single-nucleotide polymorphism (SNP) combination scores to predict Neuroticism and Sensation Seeking, with a score codification according to dominant, codominant and recessive models for common, rare allele and negative heterosis. We performed a multivariate analysis of associations (MAA) technique to explore and identify SNPs on the candidate genes. The 4 tagSNPs related to GABBR2, GNAS-AS1, DRD4 and FKBP5 candidate genes that explained the 13.8% of the Neuroticism variance, and the 4 tagSNPs related to AR, SLC6A3, DRD2 and DRD4 that explained the 14.5% of the Sensation Seeking variance. GABAergic, dopaminergic, glutamatergic and glucocorticoid receptors were associated with Neuroticism, whereas serotonin carrier, dopaminergic and androgenetic receptors associated with Sensation Seeking. These findings account for 24.87% and 29.78% of the heritable variance in base of the 4 tagSNPs for each personality variable.
The emotional processing of affective faces is an essential element of social relationships. Individual differences in personality traits such as neuroticism can influence how we manage these interactions. The objective of this study was to analyze changes in prefrontal cortex (PFC) activity in response to visual exposure to affective faces, and to ascertain whether changes in PFC activity were related to scores in neuroticism, including depression, anxiety, low self-esteem and dependence facets. Fifty-two healthy undergraduate female students participated in the present study. Results showed significant differences depending on face valence in the left and right ventrolateral PFC. We found a reduction in oxygen consumption in reaction to neutral and happy faces, and a small increase in oxygenation in reaction to angry faces both in the left and the right PFC. There were significant positive correlations in the left ventrolateral PFC between oxygenation changes during exposure to neutral and happy faces and the neuroticism factor. Anxiety and depression facets showed positive significant correlations with oxygenation changes for all Time blocks. Notice that participants with high neuroticism scores did not show differences in ventrolateral PFC activity depending on face valence. We suggest that PFC would play a protective role in response to emotional stimuli. The reduced regulatory control of PFC over the amygdala could explain vulnerability to emotional disorders in subjects with high neuroticism.
Introduction: Perinatal hypoxic-ischemic (HI) encephalopathy is defined as a neurological syndrome where the newborn suffers from acute ischemia and hypoxia during the perinatal period. New therapies are needed. The acylethanolamides, oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), possess neuroprotective properties, and they could be effective against perinatal HI. These lipid mediators act through peroxisome proliferator-activated receptors subtype α (PPARα), or transient receptor potential vanilloid (TRPV), such as TRPV subtype 1 and 4. Materials and Methods: The objectives of this study were to discern: (1) the neuroprotective role of OEA and PEA in parietotemporal cortical neurons of newborn rats and mice subjected to hypoxia, and (2) the role of the receptors, PPARα, TRPV1, and TRPV4, in neuroprotective effects. Cell culture of cortical neurons and the lactate dehydrogenase assay was carried out. The role of receptors was discerned by using selective antagonist and agonist ligands, as well as knockout (KO) PPARα mice. Results: The findings indicate that OEA and PEA exert neuroprotective effects on cultured cortical neurons subjected to a hypoxic episode. These protective effects are not mediated by the receptors, PPARα, TRPV1, or TRPV4, because neither PPARα KO mice nor receptor ligands significantly modify OEA and PEA-induced effects. Blocking TRPV4 with RN1734 is neuroprotective per se, and cotreatment with OEA and PEA is able to enhance neuroprotective effects of the acylethanolamides. Since stimulating TRPV4 was devoid of effects on OEA and PEA-induced protective effects, effects of RN1734 cotreatment seem to be a consequence of additive actions. Conclusion: The lipid mediators, OEA and PEA, exert neuroprotective effects on cultured cortical neurons subjected to hypoxia. Coadministration of OEA or PEA, and the TRPV4 antagonist RN1734 is able to enhance neuroprotective effects. These in vitro results could be of utility for developing new therapeutic tools against perinatal HI.
Previous findings demonstrate a homeostatic role for oleoylethanolamide (OEA) signaling in the ethanol-related neuroinflammation and behavior. However, extensive research is still required in order to unveil the effects of OEA on a number of neurobiological functions such as adult neurogenesis, cell survival and resident neuroimmunity that become notably altered by alcohol. Daily consumption of ethanol (10%) for 2 weeks (6.3& #x202F; +/-  1.1  g/kg/day during last 5 days) caused hypolocomotor activity in rats. This effect appears to rely on central signaling mechanisms given that alcohol increased the OEA levels, the gene expression of OEA-synthesizing enzyme Nape-pld and the number of PPAR alpha-immunoreactive neurons in the striatum. Ethanol-related neurobiological alterations such as a reduction in the number of microglial cells expressing iNOS (a cytokine-inducible immune defense) and in adult neural stem/progenitor cell (NSPC) proliferation (phospho-H3 and BrdU) and maturation (BrdU/beta 3-tubulin), as well as an increase in damage cell activity (FosB) and apoptosis (cleaved caspase 3) were also observed in the rat striatum. Pharmacological administration of OEA (10 mg/kg) for 5 days during ethanol exposure exacerbated ethanol-induced hypoloco-motion and cell apoptosis in the striatum. Interestingly, OEA abrogated the impaired effects of ethanol on PPAR alpha-positive cell population and NSPC proliferation and maturation. OEA also decreased astrocyte-related vimentin immunoreactivity and increased microglial cell population (Iba-1, iNOS) in the striatum. These results suggest that OEA-PPAR alpha signaling modulates glial activation, cell apoptosis and NSPC proliferation and maturation in response to striatal-specific neurobiological alterations induced by prolonged ethanol intake in rats.
The aim of this study was to explore the prefrontal cortex response to emotional salient stimuli in subjects with high scores in Neuroticism (and low in Sensation Seeking) or high scores in Sensation Seeking (and low in Neuroticism) personality traits,-called now Neuroticism and Sensation Seeking groups-. For this purpose, we selected 24 females (mean age: 20; SD: 1.74 years) and assigned them to two different groups according to their extreme score in personality dimensions. Ten pleasant and ten unpleasant pictures from the International Affective Picture System were presented. Neuroticism group showed significant effects for valence at the lateral prefrontal cortex in both brain hemispheres. They showed higher Oxygenation for pleasant pictures, more significantly in the left (Z = 2.49, p = 0.01) than in the right hemisphere (Z = 2.19, p = 0.03). The highest differences were registered in ventral optodes. In contrast, Sensation Seeking group did not show significant differences in hemodynamic variables as depending on the valence of the pictures. These data suggest a differential functioning of the lateral prefrontal cortex, mainly the left ventrolateral cortex, in Neuroticism group to pleasant and unpleasant visual stimuli. We hypothesize that if the lateral prefrontal activity is low, it could be the result of an over-activation of the amygdala in response to unpleasant pictures in subjects with Neuroticism or negative emotionality. These activation patterns could be related to vulnerability to emotional disorders.
Neonatal anoxia-ischemia (AI) particularly affects the central nervous system. Despite the many treatments that have been tested, none of them has proven to be completely successful. Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are acylethanolamides that do not bind to CB1 or CB2 receptors and thus they do not present cannabinoid activity. These molecules are agonist compounds of peroxisome proliferator-activator receptor alpha (PPARα), which modulates the expression of different genes that are related to glucose and lipid metabolism, inflammation, differentiation and proliferation.
The modulation of the eyeblink component of the acoustic startle reflex (ASR) has been used to study human motivation, attention, and emotion towards affective stimuli of different valence. However, sex and individual differences in personality have been rather overlooked concerning the change in the ASR to brief affective sequences. In this study, we aimed to evaluate sex differences in the ASR, together with the influence of sensitivity to punishment (SP) and sensitivity to reward (SR) in the affective modulation of the ASR to pleasant and unpleasant pictures. We addressed this topic with a latent curve model (LCM) representing the change in the ASR of an extensive group of men (n = 166) and women (n = 109). There was a significant habituation of the ASR to the pleasant pictures, and a significant sensitization of the ASR to the unpleasant pictures. Both effects were higher and more variable for women than for men. There were in addition interactive and quadratic effects of SP and SR on the ASR to the pleasant and unpleasant pictures. Men and women with extreme scores in SP, and women with low scores in SR habituated faster to the pleasant stimuli. For men scoring low in SP, higher scores in SR related with an attenuated initial ASR to the unpleasant stimuli. Women with extreme scores in SP had a higher initial ASR to the unpleasant stimuli. There were remarkable asymmetries between men and women concerning personality effects on the change in the ASR to affective stimuli.
Changes in endogenous cannabinoid homeostasis are associated with both ethanol-related neuroinflammation and memory decline. Extensive research is still required to unveil the role of endocannabinoid signaling activation on hippocampal microglial cells after ethanol exposure. Either microglial morphology, phenotype and recruitment may become notably altered after chronic alcohol-related neurodegeneration. Here, we evaluated the pharmacological effects of fatty-acid amide-hydrolase (FAAH) inhibitor URB597 (0.3 mg/kg), oleoylethanolamide (OEA, 10 mg/kg), arachidonoylethanolamide (AEA, 10 mg/kg), the CB1 receptor agonist ACEA (3 mg/kg) and the CB2 receptor agonist JWH133 (0.2 mg/kg) administered for 5 days in a rat model of subchronic (2 weeks) ethanol diet (11% v/v) exposure. URB597 turned to be the most effective treatment. URB597 increased microglial (IBA-1+) cell population, and changed morphometric features (cell area and perimeter, roughness, fractal dimension, lacunarity) associated with activated microglia in the hippocampus of ethanol-exposed rats. Regarding innate immune activity, URB597 specifically increased mRNA levels of toll-like receptor 4 (TLR4), glial fibrillary acidic protein (Gfap) and the chemokine stromal cell-derived factor 1 (SDF-1α/CXCL12), and elevated the cell population expressing the chemokine receptors CX3CR1, CCR2 and CCR4 in the ethanol-exposed rat hippocampus. Contrary to ethanol effect, URB597 reduced mRNA levels of Iba-1, Tnfα, IL-6 and the monocyte chemoattractant protein-1 (MCP-1/CCL2), as well as cell population expressing iNOS. URB597 effects on hippocampal immune system were accompanied by changes in short and long-term visual recognition memory. These results suggest that FAAH inhibition may modulates hippocampal microglial recruitment and activation that can be associated with improved hippocampal-dependent memory despite ethanol exposure.
Cocaine addiction is a chronically relapsing disorder characterized by compulsive drug-seeking and drug-taking behaviors. Previous studies have demonstrated that cocaine, as well as other drugs of abuse, alters the levels of lipid-based signaling molecules, such as N-acylethanolamines (NAEs). Moreover, brain levels of NAEs have shown sensitivity to cocaine self-administration and extinction training in rodents. Given this background, the aim of this study was to investigate the effects of repeated or acute administration of palmitoylethanolamide (PEA), an endogenous NAE, on psychomotor sensitization and cocaine-induced contextual conditioning. To this end, the potential ability of repeated PEA administration (1 or 10 mg/kg, i.p.) to modulate the acquisition of cocaine-induced behavioral sensitization (BS) and conditioned place preference (CPP) was assessed in male C57BL/6J mice. In addition, the expression of cocaine-induced BS and CPP following acute PEA administration were also studied. Results showed that repeated administration of both doses of PEA were able to block the acquisition of cocaine-induced BS. Furthermore, acute administration of both doses of PEA was able to abolish the expression of BS, while the highest dose also abolished the expression of cocaine-induced CPP. Taken together, these results indicate that exogenous administration of PEA attenuated psychomotor sensitization, while the effect of PEA in cocaine-induced CPP depended on whether PEA was administered repeatedly or acutely. These findings could be relevant to understand the role that NAEs play in processes underlying the development and maintenance of cocaine addiction.
The phytotherapy or herbal medicine is the more ancient form of medical attention and refers to the medical use of the plants or their constituents. This work is based on the analysis of the plants referred by the population as useful in the treatment of hypertension, and its chemical composition scientifically proven. Following the line of research defined by Ministery of Public Health of Ecuador on Medications, Supplies, Knowledge and Use of Medicinal Plants, in the area 19 -National System of Health-, this research was conducted on 614 hypertensive adults through interviews. The people had an average of 58 years old, predominance of female (60.09%), with basic level of schooling (29.47%) and an average of 7.2 years of suffering high blood pressure disease. Approximately 58% of the interviewed population used medicinal plants to treat the hypertension, while 42% did not use or know about medicinal plants The most widely used plants were Matricaria recutita (chamomile), Plectranthus amboinicus (oregano), Cymbopogon citratus (herb luisa (lemongrass)) and Valeriana officinalis (valerian). Among these plants, Lemongrass is the only one which its effectiveness as anti-hypertensive has been proven. The 34.03% of used plants are purchased at the and only 16.12% grew them in their backyards. The most used part of the plant was the leave and infusion the way of preparation. As part of the antihypertensive treatment the interviewed mainly consume the drugs of the pharmacological groups ACE and the ARA-II; the major mentioned conditions were visual disorders. Stress, TAG and cholesterol were mentioned as factors of risk. The medicinal use of studied plants is supported by scientific literature that also support them traditional use. Concerning the chemical composition of plant derivatives, oregano contains aromatics and oxygenated compounds, as main constituents. Chamomile contains above all flavonoids, tannins and terpenoids, lemongrass has phenolic compounds and valerian is characterized by flavonoids and terpenoids. The use of the studied plants by the population is attributed to its sedative and relaxing effects, in case of excitation nerve.