Massimo Avoli
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View article: Fast activity <i>chirp</i> patterns in focal seizures from patients and animal models
Fast activity <i>chirp</i> patterns in focal seizures from patients and animal models Open
Time–frequency analysis of focal seizure electroencephalographic signals performed with depth electrodes in human temporal lobe structures has revealed the occurrence at onset of oscillations at approximately 30–100 Hz that feature a monot…
View article: Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy
Frequency-dependent seizure-suppressing effects of optogenetic activation of septal inhibitory cells in mesial temporal lobe epilepsy Open
Mesial temporal lobe epilepsy (MTLE) is characterized by recurring focal seizures that arise from limbic areas and are often refractory to pharmacological interventions. We have reported that optogenetic stimulation of PV-positive cells in…
View article: Can in vitro studies aid in the development and use of antiseizure therapies? A report of the ILAE/AES Joint Translational Task Force
Can in vitro studies aid in the development and use of antiseizure therapies? A report of the ILAE/AES Joint Translational Task Force Open
In vitro preparations (defined here as cultured cells, brain slices, and isolated whole brains) offer a variety of approaches to modeling various aspects of seizures and epilepsy. Such models are particularly amenable to the application of…
View article: Evolution of interictal activity in models of mesial temporal lobe epilepsy
Evolution of interictal activity in models of mesial temporal lobe epilepsy Open
Interictal activity and seizures are the hallmarks of focal epileptic disorders (which include mesial temporal lobe epilepsy, MTLE) in humans and in animal models. Interictal activity, which is recorded with cortical and intracerebral EEG …
View article: Involvement of GABAergic Interneuron Subtypes in 4-Aminopyridine-Induced Seizure-Like Events in Mouse Entorhinal Cortex<i>in Vitro</i>
Involvement of GABAergic Interneuron Subtypes in 4-Aminopyridine-Induced Seizure-Like Events in Mouse Entorhinal Cortex<i>in Vitro</i> Open
Single-unit recordings performed in temporal lobe epilepsy patients and in models of temporal lobe seizures have shown that interneurons are active at focal seizure onset. We performed simultaneous patch-clamp and field potential recording…
View article: GABAB receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro
GABAB receptor outward currents are transiently disclosed by the convulsant 4-aminopyridine in vitro Open
The K+ channel blocker 4-aminopyridine (4AP) has been extensively used to investigate the mechanisms underlying neuronal network synchronization in both in vitro and in vivo animal models of focal epilepsy. 4AP-induced effects are parallel…
View article: GABAA signaling, focal epileptiform synchronization and epileptogenesis
GABAA signaling, focal epileptiform synchronization and epileptogenesis Open
Under physiological conditions, neuronal network synchronization leads to different oscillatory EEG patterns that are associated with specific behavioral and cognitive functions. Excessive synchronization can, however, lead to focal or gen…
View article: Bilateral optogenetic activation of inhibitory cells favors ictogenesis
Bilateral optogenetic activation of inhibitory cells favors ictogenesis Open
Mesial temporal lobe epilepsy (MTLE) is the most common type of focal refractory epilepsy and is characterized by recurring seizures that are often refractory to medication. Since parvalbumin-positive (PV) interneurons were recently shown …
View article: Krešimir Krnjević (1927–2021) and GABAergic inhibition: a lifetime dedication
Krešimir Krnjević (1927–2021) and GABAergic inhibition: a lifetime dedication Open
After over seven decades of neuroscience research, it is now well established that γ-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the brain. In this paper dedicated to Krešimir Krnjević (1927–2021), a pioneer and lea…
View article: Sensory processing dysregulations as reliable translational biomarkers in <i>SYNGAP1</i> haploinsufficiency
Sensory processing dysregulations as reliable translational biomarkers in <i>SYNGAP1</i> haploinsufficiency Open
Amongst the numerous genes associated with intellectual disability, SYNGAP1 stands out for its frequency and penetrance of loss-of-function variants found in patients, as well as the wide range of co-morbid disorders associated with its mu…
View article: GABAB Receptors: are they Missing in Action in Focal Epilepsy Research?
GABAB Receptors: are they Missing in Action in Focal Epilepsy Research? Open
: GABA, the key inhibitory neurotransmitter in the adult forebrain, activates pre- and postsynaptic receptors that have been categorized as GABAA, which directly open ligand-gated (or receptor-operated) ion-channels, and GABAB, which are m…
View article: Neurosteroids and Focal Epileptic Disorders
Neurosteroids and Focal Epileptic Disorders Open
Neurosteroids are a family of compounds that are synthesized in principal excitatory neurons and glial cells, and derive from the transformation of cholesterol into pregnenolone. The most studied neurosteroids—allopregnanolone and allotetr…
View article: The subiculum and its role in focal epileptic disorders
The subiculum and its role in focal epileptic disorders Open
The subicular complex (hereafter referred as subiculum), which is reciprocally connected with the hippocampus and rhinal cortices, exerts a major control on hippocampal outputs. Over the last three decades, several studies have revealed th…
View article: Faculty Opinions recommendation of A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy.
Faculty Opinions recommendation of A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy. Open
The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies sei…
View article: Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders
Update on the mechanisms and roles of high‐frequency oscillations in seizures and epileptic disorders Open
Summary High‐frequency oscillations ( HFO s) are a type of brain activity that is recorded from brain regions capable of generating seizures. Because of the close association of HFO s with epileptogenic tissue and ictogenesis, understandin…
View article: Optogenetic Low-Frequency Stimulation of Specific Neuronal Populations Abates Ictogenesis
Optogenetic Low-Frequency Stimulation of Specific Neuronal Populations Abates Ictogenesis Open
Despite many advances made in understanding the pathophysiology of epileptic disorders, seizures remain poorly controlled in approximately one-third of patients with mesial temporal lobe epilepsy. Here, we established the efficacy of cell …
View article: Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function
Decrease of SYNGAP1 in GABAergic cells impairs inhibitory synapse connectivity, synaptic inhibition and cognitive function Open
Haploinsufficiency of the SYNGAP1 gene, which codes for a Ras GTPase-activating protein, impairs cognition both in humans and in mice. Decrease of Syngap1 in mice has been previously shown to cause cognitive deficits at least in part by in…
View article: Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy
Specific imbalance of excitatory/inhibitory signaling establishes seizure onset pattern in temporal lobe epilepsy Open
Low-voltage fast (LVF) and hypersynchronous (HYP) patterns are the seizure-onset patterns most frequently observed in intracranial EEG recordings from mesial temporal lobe epilepsy (MTLE) patients. Both patterns also occur in models of MTL…
View article: <scp>GABA</scp>ergic networks jump‐start focal seizures
<span>GABA</span>ergic networks jump‐start focal seizures Open
Summary Abnormally enhanced glutamatergic excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by firm evidence, and it will be challenged here. A general reduction of unit firing has…
View article: The Long and Winding Road to Gamma-Amino-Butyric Acid as Neurotransmitter
The Long and Winding Road to Gamma-Amino-Butyric Acid as Neurotransmitter Open
This review centers on the discoveries made during more than six decades of neuroscience research on the role of gamma-amino-butyric acid (GABA) as neurotransmitter. In doing so, special emphasis is directed to the significant involvement …
View article: GABA<sub>A</sub>R modulates the bursting propensity of subicular IB cells.
GABA<sub>A</sub>R modulates the bursting propensity of subicular IB cells. Open
A: Definition of burst ratio of IB cells responses to depolarising current injection. This IB neuron generated 4 bursts made of 2 spikes (black arrowheads), followed by the generation of a single action potential (grey arrowhead). Therefor…