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Over the past decade we used genetic manipulations to study the contribution of GABAergic interneurones for rhythmic synchronous activity. We focused on the hippocampus on the medial entorhinal cortex, two brain structures that are crucially involved in spatial coding and spatial memory. Genetic manipulations included ablations of glutamate receptors or electrical coupling in GABAergic interneurones...
Autism Spectrum Disorders (ASDs) comprise a heterogeneous group of neuro-developmental abnormalities with a strong genetic component, characterized by deficits in verbal and non-verbal communication, impaired social interactions, and stereotyped behaviors. In a small percentage of cases, ASDs are associated with alterations of genes involved in synaptic function. Although rare, these point to synapses...
Increasing evidence highlights loss of RNA homeostasis as a central feature of many pathological states, including neurodegenerative diseases. The post‑transcriptional control of gene expression and its role in neurodegenerative pathologies are gaining increasing attention. Among RNA‑binding factors, ELAV proteins are master regulators of many cellular functions by influencing the RNA metabolism (from...
In the present study, the activity of isolated motor units (MUs) in the rat soleus (SOL) muscle was evoked by stimulation of thin filaments of ventral roots using constant and irregular frequency stimulation patterns. The MUs force, action potentials, and mechanomyograms (MMG) were recorded. MMG profiles were recorded with a laser distance sensor (LDS), categorized and compared with profiles obtained...
Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in genes encoding for TSC1 or TSC2. These proteins form a complex that inhibits mTORC1 signaling, which activates multiple molecular pathways leading to growth and differentiation in neurons. Lack of TSC1‑TSC2 functional complex due to mutations results in mTORC1 overactivation and neurodevelopmental syndromes such...
In the pathogenesis of central nervous system (CNS) disorders, an increasingly important role is attributed recently to unhealthy lifestyle, which consists primarily of a high caloric diet (i.e., western), chronic exposure to stress, and lack of physical activity. However, the mechanisms responsible for energy metabolism impairment induced by unhealthy lifestyles compromising CNS functions are poorly...
Epilepsy frequently develops as a result of brain insult, e.g., brain injury, stroke, inflammation, or status epilepticus, however currently there are no tools allowing us to predict which patients suffering from trauma will eventually develop epilepsy or how severe it is going to be. In recent years, small non‑coding RNAs are proposed as biomarkers for neurological diseases. Particularly microRNAs...
Neural stem cells (NSCs) – the reservoir for new neurons – can be harnessed for stem cell-based regenerative therapies in the human brain. In Alzheimer’s disease (AD), production of new neurons is suppressed due to hampered proliferative and neurogenic ability of NSCs. Therefore, understanding how the plasticity of NSCs could be induced would be important for designing stem cell‑based therapies for...
Rats are social animals that use ultrasonic vocalizations (USV) to communicate. USV are usually divided into 50 kHz calls which accompany appetitive states, and 22 kHz vocalizations which are usually associated with aversive states. Both kinds of states are known to affect animals’ heart rate (HR). Also, the polyvagal theory claims that both cardiovascular parameters and USV emission is affected by...
Mitochondria are multifunctional organelles, primarily involved in the fundamental biological process of respiration. The efficient functioning of mitochondria depends on the proper transport, sorting, and assembly of mitochondrial proteins that originate either from nuclear or mitochondrial genomes. Both nuclear and mitochondrial gene defects that result in pathological variants of proteins have...
Dementia is a global public health concern due to increasing prevalence, high morbidity, and rising socioeconomic burden. Modifying dietary behaviour could be a promising way to enhance cognition and delay or prevent dementia in later life. Several dietary factors influence dementia risk in humans, for example, vitamin E, B vitamins, omega-3 fatty acids and healthy dietary patterns, particularly the...
Recent clinical and experimental studies indicate that multiple sclerosis (MS) develops as consequence of a failed interplay between genetic and environmental factors. An ever‑growing number of risk genes have been recognised that support an autoimmune response against the body’s own brain matter. Together, these increase susceptibility to MS without actually triggering the disease. Recent experimental...
In primates, visual function is dominated by the pathway that transmits visual information from the retina, via the lateral geniculate nucleus (LGN), to the primary visual cortex (V1). Although lesions of V1 lead to blindness, it is well documented that residual visual function can be retained within scotomas caused by V1 lesions, including (largely subconscious) abilities to locate some types of...
It is generally considered that epilepsy and seizures are related to alteration in neuronal excitation/ inhibition balance. On the other hand, using an in vi‑ tro isolated guinea pig brain model of focal seizures, it has been shown that seizures start with strong firing of inhibitory interneurons, silence of principal cells, and a massive increase of extracellular potassium concentration. In order...
To understand seizures and the enduring predisposition of the brain to generate seizures, it is crucial to elucidate the dynamical pathways through which the brain reaches the seizure state. Results from computational modelling studies have predicted the existence of specific pathways to seizure. In our study, we have explored whether the transition to seizure follows principles of a universal dynamical...
Somatostatin-expressing interneurons (SST INT) are one of the types of GABAergic neurons in the brain. Inhibition through SST INT is a powerful potential mechanism for gain control in cortical networks, and it has been extensively investigated in studies on learning and memory mechanisms. Learning‑related intrinsic excitability changes of SST interneurons have been recognized in the hippocampus. The...
The zebrafish (Danio rerio) has become a new powerful model organism in biomedical research. Zebrafish possess all major neurotransmitter receptors, transporters, and enzymes, as well as, express a rich behavioral repertoire, thereby offering a wide spectrum of CNS disease models. However, our understanding of the role of zebrafish as a new emerging mainstream model in neuroscience research is still...
Abnormally enhanced excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by any firm evidence and it will be challenged here. We know in fact that a marked reduction of unit firing occurs at the onset of seizures recorded during presurgical intracranial monitoring in patients with focal, drug‑resistant epilepsies. Moreover, seizures in animal...
Given the urgent need for a disease modifying treatment of Alzheimer’s disease (AD), there is increasing interest in tau‑based therapeutics. In a comparative study, methylthioninium chloride (MTC) and leucomethylthioninium salts (LMTX®) (5‑75 mg/kg; oral administration for 3-8 weeks) were assessed preclinically in two novel transgenic tau mouse lines (Line 1, Line 66). Behavioural and histopathological...
Traditionally, plasticity was considered to belong mostly to excitatory synapses while inhibitory transmission was assumed to be relatively invariant. However, recent evidences demonstrate several types of inhibitory synaptic plasticity, raising the important question of how GABAergic and glutamatergic synaptic plasticity are coordinated during neuronal activity. Here, we found that non‑Hebbian postsynaptic...
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