The Endocannabinoid System Activation as a Neural Network Desynchronizing Mediator for Seizure Suppression

Tavares

et al. 2022

Biology

Genetic factors are among the major contributors to athletic performance. Although more than 150 genetic variants have been correlated with elite athlete status, genetic foundations of competition-facilitating behavior influencing elite performances are still scarce. This is the first study designed to examine the distribution of genetic determinants in the athletic performance of elite rink-hockey players. A total of 116 of the world’s top best rink-hockey players (28.2 ± 8.7 years old; more than 50% are cumulatively from the best four world teams and the best five Portuguese teams), who participated at the elite level in the National Rink-Hockey Championship in Portugal, were evaluated in anthropometric indicators/measurements, training conditions, sport experience and sport injuries history. Seven genetic polymorphisms were analyzed. Polymorphism genotyping was performed using the TaqMan® Allelic Discrimination Methodology. Rink-hockey players demonstrated significantly different characteristics according to sex, namely anthropometrics, training habits, sports injuries and genetic variants, such as Vitamin D Receptor (VDR) rs731236 (p < 0.05). The Fatty Acid Amide Hydrolase (FAAH) rs324420 A allele was significantly associated with improved athletic performance (AA/AC vs. CC, OR = 2.80; 95% Cl, 1.23–6.35; p = 0.014; p = 0.008 after Bootstrap) and confirmed as an independent predictor among elite rink-hockey players (adjusted OR = 2.88; 95% Cl, 1.06–7.80; p = 0.038). Our results open an interesting link from FAAH-related biology to athletic performance.

Section: Discussionmentioning

confidence: 99%

FAAH rs324420 Polymorphism Is Associated with Performance in Elite Rink-Hockey Players

Tavares

et al. 2022

Biology

“…An over-activated PV+ interneuron network may promote epileptiform synchronization among PNs through mechanisms such as post-inhibitory rebound spiking (Medeiros, Cota, Oliveira, Moreira, & Moraes, 2020). As seizure activity progresses the depolarizing effects of GABAergic signaling can further drive and synchronize population firing (Ellender, Raimondo, Irkle, Lamsa, & Akerman, 2014; Hamidi & Avoli, 2015; Huberfeld et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Reduced cholecystokinin-expressing interneuron input contributes to disinhibition of the hippocampal CA2 region in a mouse model of temporal lobe epilepsy

Whitebirch

Barnett

Santoro

et al. 2022

Preprint

A significant proportion of temporal lobe epilepsy (TLE) patients experience drug-resistant seizures associated with mesial temporal sclerosis, in which there is extensive cell loss in the hippocampal CA1 and CA3 subfields, with a relative sparing of dentate gyrus granule cells and the CA2 pyramidal neurons. A role for CA2 in seizure generation was suggested based on findings of a reduction in synaptic inhibition (Williamson & Spencer, 1994) and the presence of interictal-like spike activity in resected hippocampal tissue from TLE patients (Wittner et al., 2009). We recently found that in the pilocarpine-induced status epilepticus mouse model of TLE there was an increase in CA2 intrinsic excitability associated with a loss of CA2 synaptic inhibition. Furthermore, chemogenetic silencing of CA2 significantly reduced seizure frequency, consistent with a role of CA2 in promoting seizure generation and/or propagation (Whitebirch et al., 2022). In the present study we explored the basis of this inhibitory deficit using immunohistochemical and electrophysiological approaches. We report a widespread decrease in the density of pro-cholecystokinin-immunopositive interneurons and a functional impairment of cholecystokinin-expressing interneuron-mediated inhibition of CA2 pyramidal neurons. We also found a decrease in the density of CA2 parvalbumin-immunopositive interneurons and disruption to the pyramidal neuron-associated perisomatic perineuronal net in the CA2 subfield. These data reveal a set of pathological alterations that may disrupt inhibition of CA2 pyramidal neurons and their downstream targets in epileptic mice.

“…These results not only show that the therapeutic, diagnostic, or predictive use of ES has very much shifted from the initial dogma that synchronicity is a consequence of excitability ( Kudela et al, 2003 ), but rather that a myriad of new applications for ES arise if these two concepts (i.e., excitation/synchronicity) are untwined under the new proposed conceptual framework ( Moraes et al, 2021 ). In fact, even the rationale for how some pharmacological targets are effective in treating epilepsy has been revisited under the coincidence-detector framework ( Medeiros et al, 2020 ).…”

Section: Nps Meets the Coincidence-detection Framework: Driving The I...mentioning

confidence: 99%

On temporal scale-free non-periodic stimulation and its mechanisms as an infinite improbability drive of the brain’s functional connectogram

Cota

Cançado

Moraes

2023

Front. Neuroinform.

Self Cite

Rationalized development of electrical stimulation (ES) therapy is of paramount importance. Not only it will foster new techniques and technologies with increased levels of safety, efficacy, and efficiency, but it will also facilitate the translation from basic research to clinical practice. For such endeavor, design of new technologies must dialogue with state-of-the-art neuroscientific knowledge. By its turn, neuroscience is transitioning—a movement started a couple of decades earlier—into adopting a new conceptual framework for brain architecture, in which time and thus temporal patterns plays a central role in the neuronal representation of sampled data from the world. This article discusses how neuroscience has evolved to understand the importance of brain rhythms in the overall functional architecture of the nervous system and, consequently, that neuromodulation research should embrace this new conceptual framework. Based on such support, we revisit the literature on standard (fixed-frequency pulsatile stimuli) and mostly non-standard patterns of ES to put forward our own rationale on how temporally complex stimulation schemes may impact neuromodulation strategies. We then proceed to present a low frequency, on average (thus low energy), scale-free temporally randomized ES pattern for the treatment of experimental epilepsy, devised by our group and termed NPS (Non-periodic Stimulation). The approach has been shown to have robust anticonvulsant effects in different animal models of acute and chronic seizures (displaying dysfunctional hyperexcitable tissue), while also preserving neural function. In our understanding, accumulated mechanistic evidence suggests such a beneficial mechanism of action may be due to the natural-like characteristic of a scale-free temporal pattern that may robustly compete with aberrant epileptiform activity for the recruitment of neural circuits. Delivering temporally patterned or random stimuli within specific phases of the underlying oscillations (i.e., those involved in the communication within and across brain regions) could both potentiate and disrupt the formation of neuronal assemblies with random probability. The usage of infinite improbability drive here is obviously a reference to the “The Hitchhiker’s Guide to the Galaxy” comedy science fiction classic, written by Douglas Adams. The parallel is that dynamically driving brain functional connectogram, through neuromodulation, in a manner that would not favor any specific neuronal assembly and/or circuit, could re-stabilize a system that is transitioning to fall under the control of a single attractor. We conclude by discussing future avenues of investigation and their potentially disruptive impact on neurotechnology, with a particular interest in NPS implications in neural plasticity, motor rehabilitation, and its potential for clinical translation.