Publications by authors named "Ghestem A"

Article Synopsis
  • Myelin plasticity is essential for learning and memory in the adult brain, and any loss or alteration can impair brain function.
  • In a mouse model study, researchers found that while spontaneous remyelination can occur after demyelination, the newly formed myelin often does not match the original structure, impacting cognitive function.
  • The study revealed that even after remyelination, there were long-term cognitive deficits, including issues with memory and flexibility, likely due to changes in myelin in key brain areas like the medial prefrontal cortex and hippocampus.
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  • Cognitive deficits are a common comorbidity accompanying epilepsy, indicating that neural dynamics supporting cognitive functions are permanently changed rather than just affected by the occasional seizures.
  • The study investigates how information processing—specifically storage and sharing of information—is disrupted in the hippocampus and entorhinal cortex in rats with experimental epilepsy.
  • Findings suggest that the organization and timing of these cognitive functions in epilepsy are less ordered and more chaotic than in healthy controls, which may contribute to the widespread cognitive impairments seen in individuals with epilepsy.
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Neuropixels probes have become a crucial tool for high-density electrophysiological recordings. Although most research involving these probes is in acute preparations, some scientific inquiries require long-term recordings in freely moving animals. Recent reports have presented prosthesis designs for chronic recordings, but some of them do not allow for probe recovery, which is desirable given their cost.

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  • - Stress can lead to depression, but individual vulnerability before stressful events plays a key role in how severely someone might be affected.
  • - Researchers studied rats' sleep patterns before and after a stress event (social defeat) to identify specific sleep stages linked to vulnerability to depression using electroencephalogram recordings.
  • - The study found early and late sleep biomarkers that can predict which rats are likely to become depressed, suggesting potential for developing treatments aimed at those at high risk of stress-induced depression.
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Individuals use the observation of a conspecific to learn new behaviors and skills in many species. Whether observational learning is affected in epilepsy is not known. Using the pilocarpine rat model of epilepsy, we assessed learning by observation in a spatial task.

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  • The study investigated the antiseizure properties of Anacyclus pyrethrum (AEAPR), a plant used in traditional medicine for epilepsy treatment, particularly in conditions of oxidative stress, such as social isolation.
  • Using a pilocarpine model with socially isolated rats, researchers divided rats into treated (with AEAPR) and untreated groups, measuring their seizure activity and oxidative stress markers over time.
  • Results showed that AEAPR significantly reduced seizure frequency, duration, and severity, while also lowering oxidative stress indicators, suggesting it has potential as an effective treatment for epilepsy even in adverse conditions.
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  • The dorsal and ventral parts of the hippocampus have different energy production processes that change throughout the day and are disrupted in epilepsy.
  • In control mice, the ventral hippocampus uses more aerobic glycolysis in the morning, while the activity in the dorsal part is more stable but overall lower.
  • In an epilepsy model, the typical energy production patterns are altered, with a general decrease in metabolic activity and both parts relying more on aerobic glycolysis in the afternoon when seizure likelihood is higher.
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Gene and protein expressions display circadian oscillations, which can be disrupted in diseases in most body organs. Whether these oscillations occur in the healthy hippocampus and whether they are altered in epilepsy are not known. We identified more than 1200 daily oscillating transcripts in the hippocampus of control mice and 1600 in experimental epilepsy, with only one-fourth oscillating in both conditions.

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The nucleus reuniens (NR) is an important anatomic and functional relay between the medial prefrontal cortex (mPFC) and the hippocampus (HPC). Whether the NR controls neuronal assemblies, a hallmark of information exchange between the HPC and mPFC for memory transfer/consolidation, is not known. Using simultaneous local field potential and unit recordings in NR, HPC, and mPFC in male rats during slow oscillations under anesthesia, we identified a reliable sequential activation of NR neurons at the beginning of UP states, which preceded mPFC ones.

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Several studies suggest that neurons from the lateral region of the SuM (SuML) innervating the dorsal dentate gyrus (DG) display a dual GABAergic and glutamatergic transmission and are specifically activated during paradoxical (REM) sleep (PS). The objective of the present study is to characterize the anatomical, neurochemical and electrophysiological properties of the SuML-DG projection neurons and to determine how they control DG oscillations and neuronal activation during PS and other vigilance states. For this purpose, we combine structural connectivity techniques using neurotropic viral vectors (rabies virus, AAV), neurochemical anatomy (immunohistochemistry, in situ hybridization) and imaging (light, electron and confocal microscopy) with in vitro (patch clamp) and in vivo (LFP, EEG) optogenetic and electrophysiological recordings performed in transgenic VGLUT2-cre male mice.

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The striatum, the main input structure of the basal ganglia, is critical for action selection and adaptive motor control. To understand the neuronal mechanisms underlying these functions, an analysis of microcircuits that compose the striatum is necessary. Among these, cholinergic interneurons (ChIs) provide intrinsic striatal innervation whose dysfunction is implicated in neuropsychiatric diseases, such as Parkinson's disease and Tourette syndrome.

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The extent of the networks that control the genesis and modulation of hippocampal sharp-wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R-unchanged according to whether or not they increased their firing during SPW-Rs.

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Article Synopsis
  • Psychoactive drugs during pregnancy can harm brain development in offspring, potentially causing neurological disorders; caffeine is the most commonly consumed drug in this context.
  • A study found that offspring of THY-Tau22 transgenic mice exposed to caffeine showed earlier cognitive decline compared to those treated with water.
  • Caffeine exposure altered how neurons in the hippocampus responded to Tau pathology, suggesting it may increase the risk of early onset Alzheimer's-like symptoms in offspring.
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Many experimental approaches require housing rodents in individual cages, including in epilepsy research. However, rats and mice are social animals; and individual housing constitutes a stressful situation. The goal of the present study was to determine the effects of individual housing as compared to conditions maintaining social contact on stress markers and epilepsy.

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  • The study examines how unresolved stress from past events can increase vulnerability to epilepsy and related conditions, using an experimental model involving social defeat in rats.
  • Researchers induced epilepsy in rats through kainic acid injections after social defeat and treated some with the antioxidant Tempol, discovering that Tempol reduced seizure frequency and prevented cognitive deficits and depression-like symptoms.
  • Findings suggest that antioxidant treatment after the onset of epilepsy may be effective in modifying the disease and preventing comorbidities in individuals affected by prior stressful experiences.
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  • Recent studies on chronic EEG (electroencephalogram) in humans and rats reveal that epilepsy exhibits cyclical patterns, with rhythms occurring on circadian (daily), multi-day, and even seasonal scales.
  • Analysis of over 30 days of EEG data in male epileptic rats showed distinct patterns of interictal epileptiform activity, specifically 2-3 day and 5-7 day rhythms.
  • Seizures tended to cluster during certain phases of these rhythms, indicating that there are specific times when the risk of seizures is higher, but these patterns were inconsistent across different animals and with human interventions.
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The persistence of intractable neurological disorders necessitates novel therapeutic solutions. We demonstrate the utility of direct in situ electrophoretic drug delivery to treat neurological disorders. We present a neural probe incorporating a microfluidic ion pump (μFIP) for on-demand drug delivery and electrodes for recording local neural activity.

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Objective: Neural electrophysiology is often conducted with traditional, rigid depth probes. The mechanical mismatch between these probes and soft brain tissue is unfavorable for tissue interfacing. Making probes compliant can improve biocompatibility, but as a consequence, they become more difficult to insert into the brain.

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Gamma oscillations are involved in long-range coupling of distant regions that support various cognitive operations. Here we show in adult male rats that synchronized bursts of gamma oscillations bind the hippocampus (HPC) and prefrontal cortex (mPFC) during slow oscillations and slow-wave sleep, a brain state that is central for consolidation of memory traces. These gamma bursts entrained the firing of the local HPC and mPFC neuronal populations.

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Neuroinflammation is consistently found in many neurological disorders, but whether or not the inflammatory response independently affects neuronal network properties is poorly understood. Here, we report that intracerebroventricular injection of the prototypical inflammatory molecule lipopolysaccharide (LPS) in rats triggered a strong and long-lasting inflammatory response in hippocampal microglia associated with a concomitant upregulation of Toll-like receptor (TLR4) in pyramidal and hilar neurons. This, in turn, was associated with a significant reduction of the dendritic hyperpolarization-activated cyclic AMP-gated channel type 1 (HCN1) protein level while Kv4.

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Autoclaving, the most widely available sterilization method, is applied to poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate (PEDOT:PSS) electrophysiology devices. The process does not harm morphology or electrical properties, while it effectively kills E. coli intentionally cultured on the devices.

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After an intense and repeated stress some rats become vulnerable to depression. This state is characterized by persistent low serum BDNF concentration. Our objective was to determine whether electrophysiological markers can sign vulnerability to depression.

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Article Synopsis
  • * Researchers conducted simultaneous recordings of brain activity, blood flow, and oxygen levels in anesthetized rats, focusing on the somatosensory cortex during induced epileptiform discharges.
  • * Findings indicate a strong correlation between local field potentials (LFP) and both blood flow and tissue oxygen levels, highlighting that activity in interneurons plays a crucial role in the body's vascular and metabolic responses during seizures, unlike principal neurons.
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Article Synopsis
  • Accumulation of stressful experiences can increase the risk of developing epilepsy and related issues, but it's uncertain if this vulnerability can be anticipated or undone.
  • A study on rats showed that social defeat didn't cause depression on its own, but it did lower the threshold for seizures and led to cognitive and mood problems after epilepsy developed in 50% of cases.
  • Low levels of brain-derived neurotrophic factor (BDNF) before seizures helped identify vulnerable individuals, and administering a BDNF analog before seizures could prevent these additional problems from occurring.
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Background: Lipid lowering agent such as agonists of peroxisome proliferator-activated receptors (PPAR) are suggested as neuroprotective agents and may protect from the sequelae of brain ischemic stroke. Although the demonstration is not clearly established in human, the underlying molecular mechanism may be of interest for future therapeutic purposes. To this end, we have used our well established rodent model of ischemia-reperfusion pre-treated or not with fenofibrate or atorvastatin and performed a differential proteomics analyses of the brain and analysed the protein markers which levels returned to "normal" following pre-treatments with PPARα agonists.

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