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Leite, J. P.

Publications and source records attributed to Leite, J. P..

10 recordsLinked to original sources
bioRxiv2026

Eco-Friendly Antifouling Solutions: Hazard Assessment of Synthetic Derivatives of Natural Compounds

The accumulation of microorganisms and macroorganisms on aquatic surfaces poses economic and ecological challenges, particularly in maritime transport. Traditional antifouling methods, such as biocidal coatings containing toxic compounds like tributyltin (TBT) and copper, are effective but harmful to the environment. This study investigates eco-friendly antifouling alternatives, focusing on nature-inspired compounds (NIAFs) GBA 26 (GBA) and DPC345DHC (DH345), derived from polyphenols and flavonoids, respectively. The ecotoxicity of these compounds was evaluated using standardized assays with various species, including embryos of Danio rerio (zebrafish) (OECD TG 236), the algae Raphidocelis subcapitata (OECD TG 201), and the bacteria Vibrio fischeri (ISO 11348-2), along with nuclear receptor transactivation assays in Mytilus galloprovincialis (Mediterranean mussel). Gallic acid derivative GBA and 24h-transformation products showed low toxicity in zebrafish embryos, while dihydrochalcone DH345 inflicted developmental toxicity in zebrafish at 1 mg/L and above. Comparatively, tralopyril, a commercial biocide, exhibited significant toxicity at lower concentrations. Transcriptomic analysis of zebrafish embryos treated with GBA revealed selective gene modulation related to stress response, ion transport, and protein synthesis. Both, GBA and DH345, were shown to inhibit algae growth at 0.1 mg/L. Vibrio fischeri assay showed no toxic effects for any of the tested compounds. Nuclear receptor transactivation assays conducted with GBA revealed no activation of PPAR or PXR receptors. These findings suggest GBA and DH345 as potential eco-friendly antifouling agents with lower environmental risks than established antifoulants such as tralopyril. However, further research is needed to evaluate their potential long-term ecological impacts, particularly chronic toxicity across various organisms. This study advances the pursuit of sustainable antifouling solutions that prioritize environmental protection.

ecology↗
bioRxiv2025

Single electrically induced epileptic afterdischarge triggers synaptic weakening, AMPA receptor endocytosis and shrinkage of dendritic spines in the hippocampus

Afterdischarge (AD) is an experimental model of electrically induced seizures. When induced in limbic structures, AD is known to induce acute behavioral alterations and flattening of local field potentials that persist for a few minutes. However, impairments in more complex cognitive processes such as learning and memory, can last for hours after the seizure. Considering the mismatch between ephemeral postictal electrophysiological changes and long-lasting cognitive impairments, synaptic plasticity emerges as a possible mechanism that integrates these findings. Therefore, we used a multilevel approach to evaluate the effects of a single seizure on synaptic plasticity. First, we showed that a single AD-eliciting stimulation at the perforant pathway-dentate gyrus (PP-DG) synapse causes long-lasting decrease of evoked postsynaptic potentials. Then, we observed that this functional alteration was accompanied by shrinkage of mushroom-shaped spines in the DG. Lastly, reduced levels of p(Ser845)-GluA1 and GluA1 subunits of AMPA receptors (AMPARs) were found in the hippocampal postsynaptic density. Together, our data suggest that a seizure induces a long-term depression (LTD)-like synaptic plasticity phenomenon, which is characterized by synaptic weakening, AMPAR endocytosis, and dendritic spines shrinkage. Furthermore, the postictal changes in synaptic plasticity observed here align with the course of cognitive impairments often reported in other studies.

neuroscience↗
bioRxiv2023

Multidimensional behavioral profiles associated with resilience and susceptibility after inescapable stress

Stress-related neuropsychiatric disorders are complex conditions that are difficult to diagnose and treat due to the variety of symptoms they present with. While animal models have been instrumental in understanding their underlying mechanisms, there is an ongoing debate about the validity of behavioral measures to address specific disorders. Here, we conducted an extensive ethological characterization of behavioral variables associated with anxiety and depression and employed a multidimensional approach to investigate stress susceptibility in male Wistar rats. The rats underwent inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests over several days. Our study identified phenotypically distinct clusters, including fully characterized stress-susceptible and stress-resilient subpopulations, along with intermediate phenotypes. Reduced time in elevated plus maze open arms, diminished sucrose preference and increased escape failures consistently differentiated susceptible from resilient rats. Behavior in the forced swim test was unrelated to stress susceptibility. In conclusion, our study sheds light on the relationships between classical behavioral measures in animal models of depression, highlighting distinct patterns that differentiate susceptibility from resilience. It emphasizes the importance of a multidimensional assessment of behavioral responses in animal models for a better understanding of stress-related neuropsychiatric disorders. HIGHLIGHTSO_LIClustering of features reveals a correlation pattern that separates behavioral variables associated with susceptibility from those associated with resilience to stress C_LIO_LIMultidimensional patterns of covariation among behavioral measures distinguish helpless from non-helpless individuals and indicate independence from forced swim test behavior. C_LIO_LIClustering of individuals discriminates stressed subjects and reveals multidimensional behavioral phenotypes of resilience and susceptibility, indicating different stress-coping strategies. C_LI

animal behavior and cognition↗
bioRxiv2023

Dopamine activation modulates oscillatory synchrony in the hippocampal-prefrontal cortex circuitry

Interactions among brain networks support cognition and behavior. Oscillatory activity may contribute to this process by coordinating distant neuronal populations. A crucial step toward elucidating brain function and its emergent properties is understanding the mechanisms that dynamically modulate functional connectivity in response to environmental challenges and physiological demands. Dopamine (DA) is well-positioned to modulate this process, given its role in altering neuronal excitability and regulating oscillatory cognitive networks, such as the hippocampus-prefrontal cortex (HPC-PFC) networks. However, it is mostly unknown how dopamine modulates HPC-PFC synchrony. Here, we recorded HPC and PFC activity in rats while manipulating dopamine levels. Our results show that dopamine dose-dependently induces HPC-PFC theta synchrony. This effect was not reproduced by selective activation of D1-like (SKF-38393) or D2-like (quinpirole) receptors, nor by the D1/D2 non-selective agonist apomorphine. Thus, dopamines modulatory effects on HPC-PFC activity may depend on the precise interplay between dopamine receptor subtypes. Our findings provide evidence that dopaminergic neurotransmission plays a central role in regulating HPC-PFC oscillatory dynamics, specifically promoting synchronization in slow-frequency oscillations.

neuroscience↗
bioRxiv2022

Decoding Fear or Safety and Approach or Avoidance by Brain-Wide Network Dynamics

Discerning safety from threat and positive or negative outcomes of adversity are fundamental for mental health. Many brain structures have been implicated in both adaptive and maladaptive stress coping, however, how multiple regions function together as a network in the processing of this information is unclear. Here, we recorded local field potentials from seven regions of the mesolimbic-hippocampal-prefrontal cortical network (MLHFC) of male rats during the conditioning of a stimulus (CS) to the absence (safety) and then to the anticipation (fear) of footshocks, and during an approach-avoidance task. We developed a machine learning pipeline to investigate the relevance of specific features of oscillatory activity in the decoding of fear versus safety and approach versus avoidance. We found that decoding performance increased as a function of the number of brain regions included, reaching the best classification if all regions were considered. In addition, the best decoding was obtained from frequencies within the theta range (4-10 Hz). Remarkably, decoder models showed robust generalization within but not between individuals. Nevertheless, we were also able to identify patterns of MLHFC activity that decoded stress coping states from all rats. These patterns were characterized by increased brain-wide theta synchrony during fear and preceding approach. Our results indicate that stress coping information is encoded at the brain-wide level and highlight individual variability in this neural processing. Our findings also suggest that MLHFC network theta activity underlies active stress coping with both aversive and positive motivational valences. SIGNIFICANCE STATEMENTThe appraisal of safety versus threat and positive versus negative valence of adversity are core dimensions of emotional experience and stress coping. We developed a new behavioral protocol that discriminates states of fear, safety, approach, and avoidance in a single subject and a machine learning-based method to investigate how neural oscillations can decode such states. Our work provides evidence that stress coping is processed at multiple regions on a brain-wide level involving network oscillations at the theta frequencies, which especially synchronizes during fear and approach. We highlight the potentials of combining artificial intelligence and multi-site electroencephalography to guide therapeutic decisions in precision psychiatry and theta-boosting stimulation therapies for stress-related disorders, especially related to cognitive and motivational deficits.

neuroscience↗
bioRxiv2022

An open-source, ready-to-use and validated ripple detector plugin for the Open Ephys GUI

Sharp wave-ripples (SWRs, 100-250 Hz) are oscillatory events extracellularly recorded in the CA1 subfield of the hippocampus during sleep and quiet wakefulness. SWRs are thought to be involved in the dialogue between the hippocampus and cortical regions to promote memory consolidation during sleep and memory-guided decision making. Many studies employed closed-loop strategies to either detect and abolish SWRs within the hippocampus or manipulate other relevant areas upon ripple detection. However, the code and schematics necessary to replicate the detection system are not always available, which hinders the reproducibility of experiments among different research groups. Furthermore, information about performance is not usually reported. Here, we present the development and validation of an open-source, real-time ripple detection plugin integrated into the Open Ephys GUI. It contains a built-in movement detector based on accelerometer or electromyogram data that prevents false ripple events (due to chewing, grooming, or moving, for instance) from triggering the stimulation/manipulation device. To determine the accuracy of the detection algorithm, we first carried out simulations in Matlab with synthetic and real ripple recordings. Using a specific combination of detection parameters (amplitude threshold of 5 standard deviations above the mean, time threshold of 10 ms, and RMS block size of 7 samples), we obtained a 97% true positive rate and 2.48 false positives per minute on the real data. Next, an Open Ephys plugin based on the same detection algorithm was developed, and a closed-loop system was set up to evaluate the round trip (ripple onset-to-stimulation) latency over synthetic data. The lowest latency obtained was 34.5 {+/-} 0.5 ms. Besides contributing to increased reproducibility, we anticipate that the developed ripple detector plugin will be helpful for many closed-loop applications in the field of systems neuroscience.

neuroscience↗
bioRxiv2020

Network asynchrony underlying increased broadband gamma power

Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies the expression of cortical gamma rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband gamma power. Increased baseline broadband gamma is also a prominent characteristic in schizophrenia, and a hallmark of network alterations induced by N-methyl-D-aspartate receptor (NMDAR) antagonists such as ketamine. It has been questioned if enhanced broadband gamma power is a true rhythm, and if rhythmic PV inhibition is involved or not. It has been suggested that asynchronous and increased firing activities underlie broadband power increases spanning the gamma band. Using mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that local LFP (local field potential) oscillations and neuronal activity with decreased synchronicity generate increases in prefrontal broadband gamma power. Specifically, reduced spike time precision of both local PV interneurons and wide-spiking (WS) excitatory neurons contribute to increased firing rates, and spectral leakage of spiking activity (spike "contamination") affecting the broadband gamma band. Desynchronization was evident at multiple time scales, with reduced spike-LFP entrainment, reduced cross-frequency coupling, and fragmentation of brain states. While local application of S(+)-ketamine in wildtype mice triggered network desynchronization and increases in broadband gamma power, our investigations suggest that disparate mechanisms underlie increased power of broadband gamma caused by genetic alteration of PV interneurons, and ketamine-induced power increases in broadband gamma. Our studies, thus, confirm that broadband gamma increases can arise from asynchronous activities, and demonstrate that long-term deficiency of PV inhibition can be a contributor.

neuroscience↗
bioRxiv2019

A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance

The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (mPFC) and the hippocampus are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded CA1 and mPFC neural activities in rats during the exposure to controllable, uncontrollable, or no shocks, and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from non-stressed animals and predict resistant or helpless individuals based on neural oscillatory dynamics. We identified a pattern of enhanced CA1-mPFC theta power, synchrony, cross-frequency interaction, and neuronal coupling that strongly predicted learned resistance, and that was lacking in helpless individuals. Our findings suggest that hippocampal-prefrontal network theta activity supports cognitive mechanisms of stress coping, and its impairment may underlie vulnerability to stress-related disorders.

neuroscience↗
bioRxiv2019

Long-term potentiation prevents ketamine-induced aberrant neurophysiological dynamics in the hippocampus-prefrontal cortex pathway in vivo

N-methyl-D-aspartate receptor (NMDAr) antagonists such as ketamine (KET) produce psychotic-like behavior in both humans and animal models. NMDAr hypofunction affects normal oscillatory dynamics and synaptic plasticity in key brain regions related with schizophrenia, particularly in the hippocampus and the prefrontal cortex. In contrast, long-term potentiation (LTP) induction is known to increase glutamatergic transmission. Thus, we hypothesized that LTP could mitigate the electrophysiological changes promoted by KET. We recorded HPC-PFC local field potentials and evoked responses in urethane anesthetized rats, before and after KET administration, preceded or not by LTP induction. Our results show that KET promotes an aberrant delta-high-gamma crossfrequency coupling in the PFC and an enhancement in HPC-PFC evoked responses. LTP induction prior to KET attenuates changes in synaptic efficiency and prevents the increase in cortical gamma amplitude comodulation. These findings are consistent with evidence that increased efficiency of glutamatergic receptors attenuates cognitive impairment in animal models of psychosis. Therefore, high-frequency stimulation in HPC may be a useful tool to better understand how to prevent NMDAr hypofunction effects on synaptic plasticity and oscillatory coordination in cortico-limbic circuits.

neuroscience↗