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Medvidov, M.

Publications and source records attributed to Medvidov, M..

2 recordsLinked to original sources

Somatic Cx36 gap junctions expand the anatomical substrate for electrical coupling in the adult mouse inferior olive

The inferior olive (IO) is unique among adult mammalian brain nuclei in that its neurons communicate solely via gap junctions. For more than half a century, models of cerebellar timing, synchrony, and learning have therefore centered on how electrical coupling between olivary neurons is regulated. In the prevailing anatomical model, IO gap junctions reside on dendritic spines within olivary glomeruli, where nearby inhibitory terminals can locally regulate coupling through shunting conductances. Here we show that this view is incomplete. In the adult mouse IO, closely apposed neuronal somata are common, direct soma-soma appositions are visible by volume electron microscopy, Cx36 puncta occur at somatic contacts, and freeze-fracture replica labeling identifies Cx36-associated gap junction plaques on large continuous membrane surfaces. These soma-proximal gap junctions extend olivary electrical coupling beyond dendritic-spine glomeruli, challenging a core anatomical assumption in models of cerebellar coordination.

neuroscience↗

Biophysical underpinning of astroglial physiology probed with realistic cell models

Electrically non-excitable astroglia take up neurotransmitters, buffer extracellular K+ and generate Ca2+ signals that release molecular regulators of neural circuitry. The underlying machinery remains enigmatic, mainly because the nanoscopic, sponge-like astrocyte morphology has been difficult to access experimentally or explore theoretically. Here, we have systematically evaluated the multi-scale morphology of protoplasmic astroglia to construct a realistic multi-compartmental cell model that can be biophysically interrogated in NEURON computational environment. This approach has been implemented as an astrocyte-model builder ASTRO. As a proof of concept, we explored a hippocampal astrocyte reconstructed in silico against a battery of physiological and imaging experiments. This exploration has unveiled some basic features of astroglial physiology inaccessible empirically, such as the characteristic length of membrane voltage propagation, membrane effects of local glutamate transport, spatiotemporal dynamics of intracellular K+ redistribution, key Ca2+ buffering properties, and some basic relationships between free Ca2+ dynamics and experimental readout of fluorescent Ca2+ indicators.

neuroscience↗