Comparing Neural Correlates of Consciousness: From Psychedelics to Hypnosis and Meditation.

BACKGROUND: Pharmacological and nonpharmacological methods of inducing altered states of consciousness (ASCs) are becoming increasingly relevant in the treatment of psychiatric disorders. While comparisons between them are often drawn, to date no study has directly compared their neural correlates. METHODS: To address this knowledge gap, we directly compared 2 pharmacological methods (psilocybin 0.2 mg/kg orally [n = 23] and lysergic acid diethylamide [LSD] 100 µg orally [n = 25]) and 2 nonpharmacological methods (hypnosis [n = 30] and meditation [n = 29]) using resting-state functional connectivity magnetic resonance imaging and assessed the predictive value of the data using a machine learning approach. RESULTS: We found that 1) no network reached significance in all 4 ASC methods; 2) pharmacological and nonpharmacological interventions of inducing ASCs showed distinct connectivity patterns that were predictive at the individual level; 3) hypnosis and meditation showed differences in functional connectivity when compared directly and also drove distinct differences when jointly compared with the pharmacological ASC interventions; and 4) psilocybin and LSD showed no differences in functional connectivity when directly compared with each other, but they did show distinct behavioral-neural relationships. CONCLUSIONS: Overall, these results extend our understanding of the mechanisms of action of ASCs and highlight the importance of exploring how these effects can be leveraged in the treatment of psychiatric disorders.

Investigating functional brain connectivity patterns associated with two hypnotic states.

While there's been clinical success and growing research interest in hypnosis, neurobiological underpinnings induced by hypnosis remain unclear. In this fMRI study (which is part of a larger hypnosis project) with 50 hypnosis-experienced participants, we analyzed neural and physiological responses during two hypnosis states, comparing them to non-hypnotic control conditions and to each other. An unbiased whole-brain analysis (multi-voxel- pattern analysis, MVPA), pinpointed key neural hubs in parieto-occipital-temporal areas, cuneal/precuneal and occipital cortices, lingual gyri, and the occipital pole. Comparing directly both hypnotic states revealed depth-dependent connectivity changes, notably in left superior temporal/supramarginal gyri, cuneus, planum temporale, and lingual gyri. Multi-voxel- pattern analysis (MVPA) based seeds were implemented in a seed-to-voxel analysis unveiling region-specific increases and decreases in functional connectivity patterns. Physiologically, the respiration rate significantly slowed during hypnosis. Summarized, these findings foster fresh insights into hypnosis-induced functional connectivity changes and illuminate further knowledge related with the neurobiology of altered consciousness.

Development and Validation of an Anthropometric Equation to Predict Fat Mass Percentage in Professional and Semi-Professional Male Futsal Players.

This study aimed to (i) characterise the body composition of professional and semi-professional male futsal players, (ii) assess the validity of commonly used equations to estimate FM%, (iii) develop and cross-validate a futsal-specific FM% prediction equation. In a cross-sectional design, 78 adult male futsal players were assessed for body mass, stature, skinfolds, and girths as per the International Society for the Advancement of Kinanthropometry protocol and completed a dual-energy X-ray absorptiometry (DXA) scan for reference body composition data. Using paired-sample t-tests, the FM% from the DXA and nine published equations were compared. New sport-specific models were developed by stepwise multiple regression. Existing equations were cross-validated using the least squares regression, concordance correlation coefficient, and the Bland−Altman analyses. New equations were further cross-validated using the PRESS approach. None of the existing equations accurately predicted the DXA-derived FM% (p < 0.001; R2 ≤ 0.76, SEE ≥ 1.59; CCC ≤ 0.83; bias = −8.2% to −1.3%, limited agreement, and varying trends). The novel Bettery® equation: −0.620 + (0.159 ∗ Σ4SKF [triceps, abdominal, iliac crest, and front thigh (mm)]) + (0.120 ∗ waist girth (cm)), demonstrated a high accuracy (R2 = 0.85, SEE = 1.32%), a moderate strength of agreement (CCC = 0.92), no bias (0.2%), good agreement (±2.5%), and no trend (r = −0.157; p = 0.170) against the DXA. The Bettery® equation is the first to allow for a valid and sport-specific assessment of FM% in male futsal players.

Problemas experienciados pelo cuidador informal de pessoa idosa em situação de dependência

Introdução: Atualmente, as alterações demográficas e epidemiológicas vivenciadas em Portugal tornou-o um país envelhecido, conduzindo à necessidade de cuidar das pessoas dependentes. O cuidador informal se assume como um elemento fundamental, com responsabilidades acrescidas no cuidar dos idosos que se encontram em situação de dependência. Objetivo: Identificar os problemas experienciados / dificuldades percebidas pelos cuidadores informais de pessoas dependentes. Métodos: Realizou-se um estudo transversal e analítico. O estudo decorreu entre janeiro e novembro de 2018 na cidade de Viseu, Portugal. A amostra foi constituída por 77 cuidadores informais, sendo a maioria do gênero feminino (88,3%), com idades compreendidas entre 22 e 96 anos (média de 57,03 ± 13,52 anos), 84,4% dos cuidadores eram casados/união de fato e 70,1% viviam no meio rural. Os dados foram recolhidos por meio de um questionário constituído por variáveis sociodemográficas, referentes aos cuidadores e à pessoa dependente, pelo carers assessment of difficulties index (CADI) para identificar as necessidades do cuidador informal e pelo índice de Barthel para identificar o grau de dependência. Resultados: Verificou-se que 32,5% dos indivíduos eram totalmente dependentes, 27,2% com dependência leve, 22,1% com dependência elevada e 18,2% com dependência moderada, totalizando 72,8% dos indivíduos da amostra com dependência moderada a elevada. Os cuidadores informais manifestaram como principais dificuldades os problemas relacionais, reações à prestação de cuidados, exigências de ordem física, restrições na vida social, deficiente apoio familiar, deficiente apoio profissional e os problemas financeiros. Conclusões: De acordo com os resultados verificamos que as dificuldades mais percecionadas pelos cuidadores informais estão relacionadas com as dimensões 'Reações à prestação de cuidados'; 'Exigências de ordem física na prestação de cuidados' e 'Problemas relacionais com a pessoa dependente'.

Evaluating the Effects of Acupuncture Using a Dental Pain Model in Healthy Subjects - A Randomized, Cross-Over Trial.

Acupuncture is a complementary and nonpharmacological intervention that can be effective for the management of chronic pain in addition to or instead of medication. Various animal models for neuropathic pain, inflammatory pain, cancer-related pain, and visceral pain already exist in acupuncture research. We used a newly validated human pain model and examined whether acupuncture can influence experimentally induced dental pain. For this study, we compared the impact of manual acupuncture (real acupuncture), manual stimulation of a needle inserted at nonacupuncture points (sham acupuncture) and no acupuncture on experimentally induced dental pain in 35 healthy men who were randomized to different sequences of all 3 interventions in a within-subject design. BORG CR10 pain ratings and autonomic responses (electrodermal activity and heart rate variability) were investigated. An initial mixed model with repeated measures included preintervention pain ratings and the trial sequence as covariates. The results showed that acupuncture was effective in reducing pain intensity when compared to no acupuncture (ß = -.708, P = .002), corresponding to a medium Cohen's d effect size of .56. The comparison to the sham acupuncture revealed no statistically significant difference. No differences in autonomic responses between real and sham acupuncture were found during the intervention procedures. PERSPECTIVE: This study established a dental pain model for acupuncture research and provided evidence that experimentally induced dental pain can be influenced by either real acupuncture or manual stimulation of needles at nonacupuncture points. The data do not support that acupoint specificity is a significant factor in reducing experimental pain.

Dificuldades do cuidador informal no cuidar da pessoa dependente / Difficulties of the informal caregiver in caring for the dependent person

Introdução: Atualmente, as alterações demográficas e epidemiológicas vivenciadas em Portugal tornou-o um pais envelhecido conduzindo à necessidade de cuidar das pessoas dependentes. Surge o cuidador da pessoa dependente que, na maioria dos casos, quer por razões de afinidade, quer por razões económicas é desempenhado pelos indivíduos que se encontram na rede mais próxima da pessoa dependente denominados de cuidadores informais. Assim, este estudo tem como objetivos identificar as dificuldades percecionadas pelos cuidadores informais de pessoas dependentes; identificar as variáveis sociodemográficas e de contexto de prestação de cuidados associadas às dificuldades sentidas pelos cuidadores informais e avaliar a influência do grau de dependência dos indivíduos com as dificuldades sentidas pelos cuidadores informais. Método: Realizou-se um estudo transversal e analítico. A amostra ficou constituída por 77 cuidadores informais, sendo a maioria do género feminino (88,3%), com idades compreendidas entre os 22 e os 96 anos (uma média de 57,03±13,52 anos), 84,4% dos cuidadores eram casados / união de facto; 70,1% viviam no meio rural; a maioria possuía habilitações literárias ≤ 1º ciclo (36,4 %) e ≥ 10º ano de escolaridade; pertenciam a um agregado familiar constituído por duas pessoas, habitando com o cônjuge ou companheiro (84,4%). Recorreu-se ao questionário como instrumento de colheita de dados. O questionário era constituído por variáveis sociodemográficas e de contexto de prestação de cuidados referentes ao cuidador informal e à pessoa dependente, pela Escala Carers Assessmente of Dificultys Index (CADI) para identificar as necessidades do cuidador informal e pelo Índice de Barthel para identificar o grau de dependência. Resultados: Os cuidadores informais manifestaram como dificuldades as identificadas pelo CADI, problemas relacionais, reações à prestação de cuidaos, exigências de ordem física, restrições na vida social, deficiente apoio familiar, deficiente apoio profissional e os problemas financeiros. Verificou-se que 32,5% dos indivíduos eram totalmente dependentes, 27,2% independentes ou com dependência ligeira, 22,1% com dependência severa e 18,2% com dependência moderada, totalizando 72,8% dos indivíduos da amostra com dependência moderada a elevada. As variáveis sociodemográficas que se associaram com as dificuldades percecionadas pelo cuidador foram a idade (p=0,042), o estado civil (p=0,029) e as habilitações literárias do cuidador (p=0,041). Em relação às variáveis de contexto de prestação de cuidados verificaram-se resultados estatisticamente significativos para as variáveis: tempo de prestação de cuidados, distância de prestação de cuidados, existência de apoios sociais, existência de apoio de outras pessoas e grau de dependência. No que concerne ao grau de dependência percebeu-se que tem influencia na perceção da dificuldades relacionadas com as exigências de ordem física. Conclusões: Os cuidadores informais percecionaram algumas dificuldades fruto do cuidar a pessoa dependente. Estas dificuldades através de um acompanhamento estruturado e planeado permitindo a capacitação dos cuidadores podiam ser mitigadas. É, portanto, imperativo o papel do Enfermeiro, designadamente do Enfermeiro Especialista em Saúde Comunitária no desenvolvimento de programas e projetos de intervenção, com vista à capacitação e empowerment das comunidades com o objetivo de promover cuidados de saúde mais abrangentes e promotores da otimização de recursos.

Introduction: Currently, the demographic and epidemiological changes experienced in Portugal have made it an aged country leading to the need of taking care for people with needs. The caregiver emerges and, in most cases, either for affinity or for economic reasons, is played by individuals who are in the closest network of the dependent person and it's called informal caregivers. Thus, this study aims to identify the difficulties perceived by informal caregivers of dependent people; The objective of this study is to identify the sociodemographic and care context variables associated with the difficulties experienced by informal caregivers and to evaluate the influence of the dependence degree of individuals with the difficulties experienced by the Informal caregivers. Method: A cross-sectional and analytical study was performed. The sample consisted of 77 informal caregivers, being the majority of the female gender (88.3%), aged between 22 and 96 years (an average of 57,03 ± 13,52 years), 84.4% of the caregivers were a couple; 70.1% lived in the rural environment; The majority had literary qualifications ≤ 1st cycle (36.4%) and ≥ 10 years of schooling; belonged to a household consisting of two people, inhabiting with the spouse or partner (84.4%). The questionnaire was used as a data collection tool. The questionnaire consisted of sociodemographic variables and context of care delivery regarding the informal caregiver and the dependent person, the scale carers Assessmente of Difficultys Index (cadi) was used to identify the needs of the caregiver and the Barthel index to identify the degree of dependence. Results: Informal caregivers manifested difficulties as identified by the cadi, relational problems, reactions to the provision of care, physical demands, restrictions on social life, poor family support, poor support Professional and financial problems. It was verified that 32.5% of the individuals were totally dependent, 27.2% independent or with slight dependence, 22.1% with severe dependence and 18.2% with moderate dependence, totaling 72.8% of the individuals in the sample with moderate to high dependence. The sociodemographic variables that were associated with the difficulties perceived by the caregiver were age (P = 0,042), marital status (P = 0,029) and Caregiver's literary qualifications (P = 0,041). Regarding the variables of care context, statistically significant results were observed for the variables: time of care delivery, distance of care delivery, existence of social support, existence of Other people and degree of dependence. Regarding the degree of dependence, it was perceived that it has an influence on the perception of difficulties related to the demands of physical order. Conclusions: Informal caregivers perceived some difficulties resulting from caring for the dependent person. These difficulties through a structured and planned follow-up allowing the training of caregivers could be mitigated. It is, therefore, imperative the role of the nurse, namely the nurse specialized in community health in the development of programs and intervention projects, with a view to the training and empowerment of communities in order to promote care of Broader health and resource optimization promoters.

Neurochemical dynamics of acute orofacial pain in the human trigeminal brainstem nuclear complex.

The trigeminal brainstem sensory nuclear complex is the first central relay structure mediating orofacial somatosensory and nociceptive perception. Animal studies suggest a substantial involvement of neurochemical alterations at such basal CNS levels in acute and chronic pain processing. Translating this animal based knowledge to humans is challenging. Human related examining of brainstem functions are challenged by MR related peculiarities as well as applicability aspects of experimentally standardized paradigms. Based on our experience with an MR compatible human orofacial pain model, the aims of the present study were twofold: 1) from a technical perspective, the evaluation of proton magnetic resonance spectroscopy at 3 T regarding measurement accuracy of neurochemical profiles in this small brainstem nuclear complex and 2) the examination of possible neurochemical alterations induced by an experimental orofacial pain model. Data from 13 healthy volunteers aged 19-46 years were analyzed and revealed high quality spectra with significant reductions in total N-acetylaspartate (N-acetylaspartate + N-acetylaspartylglutamate) (-3.7%, p = 0.009) and GABA (-10.88%, p = 0.041) during the pain condition. These results might reflect contributions of N-acetylaspartate and N-acetylaspartylglutamate in neuronal activity-dependent physiologic processes and/or excitatory neurotransmission, whereas changes in GABA might indicate towards a reduction in tonic GABAergic functioning during nociceptive signaling. Summarized, the present study indicates the applicability of 1H-MRS to obtain neurochemical dynamics within the human trigeminal brainstem sensory nuclear complex. Further developments are needed to pave the way towards bridging important animal based knowledge with human research to understand the neurochemistry of orofacial nociception and pain.

Reproducibility of Neurochemical Profile Quantification in Pregenual Cingulate, Anterior Midcingulate, and Bilateral Posterior Insular Subdivisions Measured at 3 Tesla.

The current report assessed measurement reproducibility of proton magnetic resonance spectroscopy at 3 Tesla in the left and right posterior insular, pregenual anterior cingulate, and anterior midcingulate cortices. Ten healthy male volunteers aged 21-30 years were tested at four different days, of which nine were included in the data analysis. Intra- and inter-subject variability of myo-inositol, creatine, glutamate, total-choline, total-N-acetylaspartate, and combined glutamine-glutamate were calculated considering the influence of movement parameters, age, daytime of measurements, and tissue composition. Overall mean intra-/inter-subject variability for all neurochemicals combined revealed small mean coefficients of variation across the four regions: 5.3/9.05% in anterior midcingulate, 6.6/8.84% in pregenual anterior cingulate, 7.3/10.00% in left posterior and 8.2/10.55% in right posterior insula. Head movement, tissue composition and day time revealed no significant explanatory variance contribution suggesting a negligible influence on the data. A strong correlation between Cramer-Rao Lower Bounds (a measure of fitting errors) and the mean intra-subject coefficients of variation (r = 0.799, p < 0.001) outlined the importance of low fitting errors in order to obtain robust and finally meaningful measurements. The present findings confirm proton magnetic resonance spectroscopy as a reliable tool to measure brain neurochemistry in small subregions of the human brain.

Equal pain-Unequal fear response: enhanced susceptibility of tooth pain to fear conditioning.

Experimental fear conditioning in humans is widely used as a model to investigate the neural basis of fear learning and to unravel the pathogenesis of anxiety disorders. It has been observed that fear conditioning depends on stimulus salience and subject vulnerability to fear. It is further known that the prevalence of dental-related fear and phobia is exceedingly high in the population. Dental phobia is unique as no other body part is associated with a specific phobia. Therefore, we hypothesized that painful dental stimuli exhibit an enhanced susceptibility to fear conditioning when comparing to equal perceived stimuli applied to other body sites. Differential susceptibility to pain-related fear was investigated by analyzing responses to an unconditioned stimulus (UCS) applied to the right maxillary canine (UCS-c) vs. the right tibia (UCS-t). For fear conditioning, UCS-c and USC-t consisted of painful electric stimuli, carefully matched at both application sites for equal intensity and quality perception. UCSs were paired to simple geometrical forms which served as conditioned stimuli (CS+). Unpaired CS+ were presented for eliciting and analyzing conditioned fear responses. Outcome parameter were (1) skin conductance changes and (2) time-dependent brain activity (BOLD responses) in fear-related brain regions such as the amygdala, anterior cingulate cortex, insula, thalamus, orbitofrontal cortex, and medial prefrontal cortex. A preferential susceptibility of dental pain to fear conditioning was observed, reflected by heightened skin conductance responses and enhanced time-dependent brain activity (BOLD responses) in the fear network. For the first time, this study demonstrates fear-related neurobiological mechanisms that point toward a superior conditionability of tooth pain. Beside traumatic dental experiences our results offer novel evidence that might explain the high prevalence of dental-related fears in the population.

Match analysis in football: a systematic review.

Abstract The main focus of this paper was to review the available literature on match analysis in adult male football. The most common research topics were identified, their methodologies described and the evolutionary tendencies of this research area systematised. A systematic review of Institute for Scientific Information (ISI) Web of Knowledge database was performed according to PRISMA (Preferred Reporting Items for Systematic reviews and Meta-analyses) guidelines. The following keywords were used: football and soccer, each one associated with the terms: match analysis, performance analysis, notational analysis, game analysis, tactical analysis and patterns of play. Of 2732 studies initially identified, only 53 were fully reviewed, and their outcome measures abstracted and analysed. Studies that fit all inclusion criteria were organised according to their research design as descriptive, comparative or predictive. Results showed that 10 studies focused predominantly on a description of technical, tactical and physical performance variables. From all comparative studies, the dependent variables more frequently used were "playing position" and "competitive level". Even though the literature stresses the importance of developing predictive models of sports performance, only few studies (n = 8) have focused on modelling football performance. Situational variables like game location, quality of opposing teams, match status and match half have been progressively included as object of research, since they seem to work as effective covariables of football performance. Taking into account the limitations of the reviewed studies, future research should provide comprehensive operational definitions for the studied variables, use standardised categories and description of activities and participants, and consider integrating the situational and interactional contexts into the analysis of football performance.

Prevalence of nonfunctional overreaching/overtraining in young English athletes.

PURPOSE: Nonfunctional overreaching and overtraining (NFOR/OT) in adults can lead to significant decrements in performance, combined with physical and psychological health problems. Little is known about this condition in young athletes by comparison; thus, the aim of the study was to assess the incidence and symptomatology of NFOR/OT in young English athletes. METHODS: Three hundred seventy-six athletes (131 girls and 245 boys, age=15.1±2.0 yr) completed a 92-item survey about NFOR/OT. The sample included athletes competing at club to international standards across 19 different sports. Athletes were classified as NFOR/OT if they reported persistent daily fatigue and a significant decrement in performance that lasted for long periods of time (i.e., weeks to months). Data were analyzed using the Mann-Whitney U and the Kolmogorov-Smirnov nonparametric tests. Significant predictors of NFOR/OT were identified using logistic regression analysis. RESULTS: One hundred ten athletes (29%) reported having been NFOR/OT at least once. The incidence was significantly higher in individual sports (P<0.01), low-physical demand sports (P<0.01), females (P<0.01), and at the elite level (P<0.01). Training load was not a significant predictor of NFOR/OT; however, competitive level and gender accounted for a small (4.7% and 1.7%, respectively) but significant explanatory variance of NFOR/OT (P<0.05). CONCLUSIONS: Approximately one-third of young athletes have experienced NFOR/OT, making this an issue for parents and coaches to recognize. OT is not solely a training load-related problem with both physical and psychosocial factors identified as important contributors.

Overtraining and elite young athletes.

In comparison to adults, our knowledge of the overtraining syndrome in elite young athletes is lacking. The evidence indicates an incidence rate of ∼20-30%, with a relatively higher occurrence seen in individual sport athletes, females and those competing at the highest representative levels. The most commonly reported symptoms are similar to those observed in over trained adult athletes: increased perception of effort during exercise, frequent upper respiratory tract infections, muscle soreness, sleep disturbances, loss of appetite, mood disturbances, shortness of temper, decreased interest in training and competition, decreased self-confidence, inability to concentrate. The association between training load and overtraining is unclear, and underlines the importance of taking a holistic approach when trying to treat or prevent overtraining in the young athlete so that both training and non-training stressors are considered. Of particular relevance to the issue of overtraining in the elite young athlete are the development of a unidimensional identity, the lack of autonomy, disempowerment, perfectionist traits, conditional love, and unrealistic expectations. Overtraining syndrome is a complex phenomenon with unique and multiple antecedents for each individual; therefore, an open-minded and comprehensive perspective is needed to successfully treat/prevent this in the young athlete.

Trainability of young athletes and overtraining.

Exercise adaptations to strength, anaerobic and aerobic training have been extensively studied in adults, however, young people appear to respond differently to such exercise stimulus in comparison to adults. In addition, because overtraining in young athletes has received little attention, this important area is also discussed. Resistance training in children can be safe and effective. It has the potential to improve sport performance, enhance body composition and reduce the rate of sport incurred injury. Furthermore, with the appropriate stimulus, prepubertal and adolescent athletes can show significant increments in muscle strength (13 - 30%). Children can improve anaerobic power (3%-10% Mean Power and 4%-20% in Peak Power), although the mechanisms responsible for the improvements in children remain unclear. Children show a 'reduced' trainability of peak VO2 in comparison to adults. Nevertheless, their aerobic power is trainable, with improvements reported at approximately 5%. Moreover, improvements in other variables like exercise economy or lactate threshold may occur without significant changes in peak VO2 The limited evidence available indicates that overtraining is occurring in young athletes (30% prevalence), highlighting the importance of further research in to all the possible contributing factors - physiological, psychological and emotional - when investigating overtraining. Key pointsChildren's strength, anaerobic and aerobic power is trainable, although the improvements may be smaller than seen in adults.Children can demonstrate significant gains in muscle strength with resistance training (13 - 30%).Improvements in mean power (3 - 10%) and peak power (4 - 20%) are reported in children.Aerobic fitness can improve with training in children by approximately 5%.Limited available evidence indicates an occurrence of overtraining in young athletes of around 30%.

Effect of the zinc chelator N,N,N',N'-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) on hippocampal mossy fiber calcium signals and on synaptic transmission.

An important pool of chelatable zinc is present in the synaptic vesicles of mossy fiber terminals from hippocampal CA3 area, being zinc released following single or repetitive electrical stimulation. Previous studies have suggested different synaptic roles for released mossy fiber zinc, including the inhibition of presynaptic calcium and of postsynaptic N-methyl-D-aspartate (NMDA) and gamma amino-butyric acid (GABAA) receptors. The effect of endogenously released zinc on mossy fiber long-term potentiation (LTP) induction also is not yet established. We have investigated the effect of the permeant zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) on mossy fiber calcium and on synaptic transmission, before and during the application of LTP-inducing stimulation. We have found, using the calcium indicator Fura-2, that single and tetanically-evoked mossy fiber calcium signals are both enhanced in the presence of 20 microM TPEN, while the single field potentials are unaffected. As expected, no effect was observed on the single calcium signals or field potentials obtained at the CA3-CA1 synapses, from the CA1 area, which has a lower concentration of vesicular zinc. These results support the idea that at the hippocampal mossy fiber synapses, released zinc inhibits presynaptic calcium mechanisms. A higher concentration of TPEN (100 microM) significantly reduced mossy fiber synaptic transmission but did not prevent the induction of mossy fiber LTP, suggesting that zinc is not required for the formation of this form of LTP.

Effect of the zinc chelator N, N, N',N'- tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) on hippocampal mossy fiber calcium signals and on synaptic transmission

An important pool of chelatable zinc is present in the synaptic vesicles of mossy fiber terminals from hippocampal CA3 area, being zinc released following single or repetitive electrical stimulation. Previous studies have suggested different synaptic roles for released mossy fiber zinc, including the inhibition of presynaptic calcium and of postsynaptic N-methyl-D-aspartate (NMDA) and gamma amino-butiric acid (GABA A) receptors. The effect of endogenously released zinc on mossy fiber long-term potentiation (LTP) induction also is not yet established. We have investigated the effect of the permeant zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) on mossy fiber calcium and on synaptic transmission, before and during the application of LTP-inducing stimulation. We have found, using the calcium indicator Fura-2, that single and tetanically-evoked mossy fiber calcium signals are both enhanced in the presence of 20 ìM TPEN, while the single field potentials are unaffected. As expected, no effect was observed on the single calcium signals or field potentials obtained at the CA3-CA1 synapses, from the CA1 area, which has a lower concentration of vesicular zinc. These results support the idea that at the hippocampal mossy fiber synapses, released zinc inhibits presynaptic calcium mechanisms. A higher concentration of TPEN (100 ìM) significantly reduced mossy fiber synaptic transmission but did not prevent the induction of mossy fiber LTP, suggesting that zinc is not required for the formation of this form of LTP.