Neuronal Glutamatergic Network Electrically Wired with Silent But Activatable Gap Junctions.

It is widely assumed that electrical synapses in the mammalian brain, especially between interneurons, underlie neuronal synchrony. In the hippocampus, principal cells also establish electrical synapses with each other and have also been implicated in network oscillations, whereby the origin of fast electrical activity has been attributed to ectopic spikelets and dendro-dendritic or axo-axonal gap junctions. However, if electrical synapses were in axo-dendritic connections, where chemical synapses occur, the synaptic events would be mixed, having an electrical component preceding the chemical one. This type of communication is less well studied, mainly because it is not easily detected. Moreover, a possible scenario could be that an electrical synapse coexisted with a chemical one, but in a nonconductive state; hence, it would be considered inexistent. Could chemical synapses have a quiescent electrical component? If so, can silent electrical synapses be activated to be detected? We addressed this possibility, and we here report that, indeed, the connexin-36-containing glutamatergic mossy fiber synapses of the rat hippocampus express previously unrecognized electrical synapses, which are normally silent. We reveal that these synapses are pH sensitive, actuate in vitro and in vivo, and that the electrical signaling is bidirectional. With the simultaneous recording of hundreds of cells, we could reveal the existence of an electrical circuit in the hippocampus of adult rats of either sex consisting of principal cells where the nodes are interregional glutamatergic synapses containing silent but ready-to-use gap junctions.SIGNIFICANCE STATEMENT In this work, we present a series of experiments, both in vitro and in vivo, that reveal previously unrecognized silent pH-sensitive electrical synapses coexisting in one of the best studied glutamatergic synapses of the brain, the mossy fiber synapse of the hippocampus. This type of connectivity underlies an "electrical circuit" between two substructures of the adult rat hippocampus consisting of principal cells where the nodes are glutamatergic synapses containing silent but ready-to-use gap junctions. Its identification will allow us to explore the participation of such a circuit in physiological and pathophysiological functions and will provide valuable conceptual tools to understanding computational and regulatory mechanisms that may underlie network activity.

Analysis of the psychometric properties of the five-factor self-concept questionnaire (AF-5) in Spanish students during the COVID-19 lockdown.

The present research aims to analyse the psychometric properties of the AF5 questionnaire for its adaptation for use with young people during a lockdown period. Research was conducted with a sample of 534 students aged between 13 and 17 years (M = 14.49; SD = 1.805). Exploratory factor analysis was conducted using the FACTOR program and confirmatory factor analysis was conducted using the M-PLUS 7 program. Results indicate that a four-dimensional model is most appropriate for bringing together the emotional and physical dimensions. Further, 11 items were removed due to poor factor loadings. The majority of factors were directly and positively correlated (99%; p < .01). The data obtained supports conclusions that the AF-5 meets validity and reliability requirements for it to be considered a useful instrument for use with young people during the COVID-19 lockdown period.

Early Appearance and Spread of Fast Ripples in the Hippocampus in a Model of Cortical Traumatic Brain Injury.

Fast ripples (FRs; activity of >250 Hz) have been considered as a biomarker of epileptic activity in the hippocampus and entorhinal cortex; it is thought that they signal the focus of seizure generation. Similar high-frequency network activity has been produced in vitro by changing extracellular medium composition, by using pro-epileptic substances, or by electrical stimulation. Here we study the propagation of these events between different subregions of the male rat hippocampus in a recently introduced experimental model of FRs in entorhinal cortex-hippocampal slices in vitro By using a matrix of 4096 microelectrodes, the sites of initiation, propagation pathways, and spatiotemporal characteristics of activity patterns could be studied with unprecedented high resolution. To this end, we developed an analytic tool based on bidimensional current source density estimation, which delimits sinks and sources with a high precision and evaluates their trajectories using the concept of center of mass. With this methodology, we found that FRs can arise almost simultaneously at noncontiguous sites in the CA3-to-CA1 direction, underlying the spatial heterogeneity of epileptogenic foci, while continuous somatodendritic waves of activity develop. An unexpected, yet important propagation route is the propagation of activity from CA3 into the hilus and dentate gyrus. This pathway may cause reverberating activation of both regions, supporting sustained pathological network events and altered information processing in hippocampal networks.SIGNIFICANCE STATEMENT Fast ripples (FRs) have been considered as a biomarker of epileptic activity and may signal the focus of seizure generation. In a model of traumatic brain injury in the rat, FRs appear in the hippocampus within a couple of hours after an extrahippocampal, cortical lesion. We analyzed the origin and dynamics of the FRs in the hippocampus using massive electrophysiological recordings, allowing an unprecedented high spatiotemporal resolution. We show that FRs originate in distinct and noncontiguous locations within the CA3 region and uncover, with high precision, the extent and dynamics of their current density. This activity propagates toward CA1 but also backpropagates to the hilus and the dentate gyrus, suggesting activation of defined microcircuits that can sustain recurrent excitation.

Effect of Melatonin Supplementation on Antioxidant Status and DNA Damage in High Intensity Trained Athletes.

The aim of the study was to evaluate the effect of melatonin supplementation on antioxidant capacity and DNA damage in high intensity interval training (HIIT) athletes. A 2-week randomised, double-blinded, placebo-controlled trial with two groups was conducted. Placebo (PG) and melatonin (MG) (20 mg/d) athletes were monitored over a two-week period of HIIT and strength training. The total antioxidant capacity (TAC) and the glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were analysed in blood samples. DNA damage was measured in isolated lymphocytes by comet assay prior to and immediately after exercise. The supplementation increased plasma melatonin levels in the melatonin-treated group (p<0.05) after two weeks of intervention. Analysis of antioxidant status indicated higher (p<0.05) TAC and GPx in MG than PG post-intervention. No differences were found in SOD enzyme activity. DNA damage was diminished in MG (p<0.05) compared to PG in post-training conditions. Antioxidant status was associated with DNA damage (r=-0.679; p=0.047) in the melatonin-treated athletes. The present study suggest that melatonin supplementation improves antioxidant status and may prove to have beneficial effects preventing DNA damage induced by high intensity training.

Violent Behaviour and Emotional Intelligence in Physical Education: The Effects of an Intervention Programme.

Violent behaviour in the secondary education stage is a serious concern that comes from low emotional control. Judo is a sport that requires self-control and high emotional competence to mitigate aggressive behaviours. This research presents the objectives of analysing the correlations of different types of aggressive behaviours before an intervention program with those after said program, as well as study the effect of emotions on aggressive behaviours before and after the intervention program through multigroup structural equation modelling. A quasi-experimental study was planned. It used a pre-test-post-test design in a population of 139 secondary school students (M = 15.76; SD = 1.066). The instruments were an ad hoc questionnaire, the Schutte Self-Report Inventory and the Violent Behaviour at School Scale. The data show that the intervention decreased the correlations between different types of violent behaviours. The results show an increase in the effect of emotional intelligence on mitigating aggressive attitudes. The promotion and use of contact sports is necessary to prevent the emergence of aggressive behaviours within a school environment.

Effectiveness of a Judo Intervention Programme on the Psychosocial Area in Secondary School Education Students.

Currently, many combat sports are pedagogically conceived as uneducational and unreliable for the development of young people. The present research aims to investigate the influence of a Judo intervention programme on the motivational climate towards sport, aggressive behaviour, emotional intelligence, and self-concept in secondary school students and to establish the relationships between them. This objective was broken down into (a) developing an explanatory model of the variables mentioned above and (b) testing the model equations through a multi-group analysis in terms of pre-test and post-test. The present study conducted a pre-post-test quasi-experimental design with a single experimental group. The sample consisted of a total of 139 adolescents (12.67 ± 1.066), 50.4% of whom were male (n = 70) and 49.6% female (n = 69). The results show that the intervention decreased all types of aggression and increased levels of emotional intelligence. An increase in social, physical and academic self-concept and decreases in the family and emotional areas were also observed. Finally, for the motivational climate, a tendency towards the ego climate to the detriment of the task climate was observed. It is concluded that the Judo intervention programme is effective in decreasing aggressive behaviour and effective in increasing levels of emotional intelligence and self-concept.

Differential frequency-dependent antidromic resonance of the Schaffer collaterals and mossy fibers.

To better understand information transfer along the hippocampal pathways and its plasticity, here we studied the antidromic responses of the dentate gyrus (DG) and CA3 to activation of the mossy fibers and Schaffer collaterals, respectively, in hippocampal slices from naïve and epileptic rats. We applied trains of 600 electrical stimuli at functionally meaningful frequencies (θ, ß/γ and γ). The responses of the DG to θ frequency trains underwent rapid potentiation that lasted about 400 stimuli, after which they progressively returned to control value. At ß/γ and γ frequencies, however, the initial potentiation was followed by a strong frequency-dependent depression within the first 50 stimuli. In kindled animals, the initial potentiation was stronger than in control preparations and the resonant phase at θ frequency lasted longer. In contrast, CA3 responses were exponentially depressed at all frequencies, but depression was significantly less intense at θ frequency in epileptic preparations. Failure of fibers to fire action potentials could account for some of the aforementioned characteristics, but waveforms of the intracellular action potentials also changed as the field responses did, i.e., half-duration and time-to-peak increased in both structures along the stimulation trains. Noteworthy, block of glutamate and GABA ionotropic receptors prevented resonance and reduced the depression of antidromic responses to ß/γ and γ stimulation recorded in the DG, but not in CA3. We show that the different behavior in the information transfer along these pathways depends on the frequency at which action potentials are generated, excitability history and anatomical features, including myelination and tortuosity. In addition, the mossy fibers are endowed with ionotropic receptors and terminal active properties conferring them their sui generis non-passive antidromic responses.

Entorhinal cortex lesions result in adenosine-sensitive high frequency oscillations in the hippocampus.

Entorhinal cortex (EC) projections to the hippocampus run along the perforant path and activate the hippocampal area CA3 and the dentate gyrus (DG), which, in turn, drives CA3. Because cortical trauma damages the source of inputs to the hippocampus, we hypothesize that such an event can be reflected in immediate alterations of the hippocampal oscillatory activity. We here explore whether acute, localized disruption of EC-EC connectivity is involved in the generation or modulation of high frequency oscillations (HFOs) in the hippocampus. We conducted in vitro electrophysiological recordings in CA3 and DG of combined EC-hippocampal transversal slices prepared from intact brains and from brains with a spatially defined, transversal cut of the EC made in situ, 2h before in vitro recordings commenced. We also determined if pharmacological manipulations of the adenosine system modulated the fast oscillatory activity. EC-hippocampal slices prepared from brains, in which a transversal lesion of the EC was uni- or bilaterally conducted in situ, displayed spontaneous epileptiform events with superimposed ripples (150-250 Hz) and fast ripples (>250 Hz), whereas those obtained from non-lesioned brains did not have spontaneous HFOs. However, in the latter, high frequency stimulation applied to the perforant path produced ripple activity in area CA3. Spontaneous fast ripples were prevented by conducting the slicing procedure and incubating the slices both in a Na(+)-free medium and in a low Ca(++)-high Mg(++) medium for an hour before recording commenced, under normal Na(+) concentration. Activation of A1, but not A2, receptors produced a strong inhibition of the incidence and spectral power of fast ripples but did not change their intrinsic frequency. Our data show that the disruption of EC-to-EC connections can immediately disinhibit hippocampal CA3 area to generate HFOs on top of epileptiform events, probably constituting an irritating focus long before overt epileptic activity can be detected behaviorally. Therefore, the activation of the adenosinergic system can possibly be regarded as an immediate intervention strategy to avoid epileptogenesis.