ORCID Profile
0000-0002-2232-6146
Current Organisations
Vitec Appva AB
,
Mendi.io
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Publisher: Society for Neuroscience
Date: 06-05-2015
DOI: 10.1523/JNEUROSCI.4747-14.2015
Abstract: Myelination and voltage-gated ion channel clustering at the nodes of Ranvier are essential for the rapid saltatory conduction of action potentials. Whether myelination influences the structural organization of the axon initial segment (AIS) and action potential initiation is poorly understood. Using the cuprizone mouse model, we combined electrophysiological recordings with immunofluorescence of the voltage-gated Nav1.6 and Kv7.3 subunits and anchoring proteins to analyze the functional and structural properties of single demyelinated neocortical L5 axons. Whole-cell recordings demonstrated that neurons with demyelinated axons were intrinsically more excitable, characterized by increased spontaneous suprathreshold depolarizations as well as antidromically propagating action potentials ectopically generated in distal parts of the axon. Immunofluorescence examination of demyelinated axons showed that βIV-spectrin, Nav1.6, and the Kv7.3 channels in nodes of Ranvier either dissolved or extended into the paranodal domains. In contrast, while the AIS in demyelinated axons started more closely to the soma, ankyrin G, βIV-spectrin, and the ion channel expression were maintained. Structure–function analysis and computational modeling, constrained by the AIS location and realistic dendritic and axonal morphologies, confirmed that a more proximal onset of the AIS slightly reduced the efficacy of action potential generation, suggesting a compensatory role. These results suggest that oligodendroglial myelination is not only important for maximizing conduction velocity, but also for limiting hyperexcitability of pyramidal neurons.
Publisher: Proceedings of the National Academy of Sciences
Date: 05-12-2016
Abstract: Neurons generate highly reliable and temporally precise action potentials with a spatial onset in the axon initial segment. The axon initial segment location relative to the soma is, however, highly variable across neurons within the same cell class. Here, we experimentally and theoretically investigated the structure–function relationship of axon distances in neocortical pyramidal neurons. We discovered a scaling principle between the size of the dendritic tree and the axon distance supported by the cable properties and electrophysiological recordings. The work reveals that axons are not randomly positioned but covary with dendrites normalizing the somatic action potential in the face of erse cellular morphologies.
Publisher: eLife Sciences Publications, Ltd
Date: 24-12-2021
Publisher: eLife Sciences Publications, Ltd
Date: 10-01-2022
DOI: 10.7554/ELIFE.73827
Abstract: Parvalbumin-positive (PV + ) γ-aminobutyric acid (GABA) interneurons are critically involved in producing rapid network oscillations and cortical microcircuit computations, but the significance of PV + axon myelination to the temporal features of inhibition remains elusive. Here, using toxic and genetic mouse models of demyelination and dysmyelination, respectively, we find that loss of compact myelin reduces PV + interneuron presynaptic terminals and increases failures, and the weak phasic inhibition of pyramidal neurons abolishes optogenetically driven gamma oscillations in vivo. Strikingly, during behaviors of quiet wakefulness selectively theta rhythms are lified and accompanied by highly synchronized interictal epileptic discharges. In support of a causal role of impaired PV-mediated inhibition, optogenetic activation of myelin-deficient PV + interneurons attenuated the power of slow theta rhythms and limited interictal spike occurrence. Thus, myelination of PV axons is required to consolidate fast inhibition of pyramidal neurons and enable behavioral state-dependent modulation of local circuit synchronization.
Publisher: Frontiers Media SA
Date: 27-02-2017
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Mustafa S. Hamada.