Fast calcium transients in neuronal spines driven by extreme statistics

Abstract

Extreme statistics describe the distribution of rare events that can dene the timescales of transduction within cellular microdomains. We combine biophysical modeling and analysis of live-cell calcium imaging to explain the fast calcium transient in spines. We show that in the presence of a spine apparatus (SA), which is an extension of the smooth endoplasmic reticulum (ER), calcium transients during synaptic inputs rely on rare and extreme calcium ion trajectories. Using numerical simulations, we predicted the asymmetrical distributions of Ryanodine receptors and SERCA pumps that we conrmed experimentally. When calcium ions are released in the spine head, the fastest ions arriving at the base determine the transient timescale through a calcium-induced calcium release mechanism. In general,the fastest particles arriving at a small target are likely to be a generic mechanism that determines the timescale of molecular transduction in cellular neuroscience.Signicance statement: Intrigued by fast calcium transients of few milliseconds in dendritic spines, we investigated its underlying biophysical mechanism. We show here that it is generated by the diusion of the fastest calcium ions when the spine contains a Spine Apparatus, an extension of the endoplasmic reticulum. This timescale is modulated by the initial number of released calcium ions and the asymmetric distribution of its associated calcium release associated Ryanodyne receptors, present only at the base of a spine. This 1 not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission.The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/290734 doi: bioRxiv preprint first posted online Mar. 28, 2018; novel mechanism of calcium signaling that we have unraveled here is driven by the fastest particles. To conclude, the rate of arrival of the fastest particles (ions) to a small target receptor denes the timescale of activation instead of the classical forward rate of chemical reactions introduced by von Smoluchowski in 1916. Applying this new rate theory to transduction should rene our understanding of the biophysical mechanisms underlying molecular signaling.

Dendritic spine geometry and spine apparatus organization govern the spatiotemporal dynamics of calcium

“…Dendritic spines have a unique set of shapes and recently the size and shape distribution of spines has been linked to their physiological function ( Hering and Sheng, 2001 ; Berry and Nedivi, 2017 ). Additionally, only ∼14% of spines have a specialized ER known as the SpApp ( Basnayake et al, 2018 Preprint ; Jedlicka et al, 2008 ), which serves as a calcium store ( Wuytack et al, 2002 ; Jedlicka et al, 2008 ). Indeed, calcium dynamics in dendritic spines are quite complex.…”

Interactions neurogliales dans la physiologie et les pathologies cérébrales / Neuroglial interactions in cerebral physiology and pathologies

“…We also recently revealed that Cx30, one of the two astroglial gap junction channel subunit, which is a determinant of astroglial synapse coverage controlling synaptic efficacy and hippocampal-based memory via an unprecedented non channel function controlling the astroglial coverage of synapses (Pannasch et al, 2014), also controls hippocampal neuronal population bursts and associated convulsive behavior (Pannasch et al, 2019). We report that Cx30 expression is increased in vivo by seizures and that it controls in turn the severity of behavioral seizures.…”

Asymptotics for the fastest among N stochastic particles: role of an extended initial distribution and an additional drift component

“…Transient molecular activation in many cellular processes, such as gene transcription [1], calcium activity in neuronal protrusion [2] or biochemical pathways associated with a secondary messenger transduction [3] often occur in geometrical restricted micro-compartments, where the initial distribution of the source is well separated from the target site. To guarantee a reliable and fast activation, these processes are carried out by multiple redundant particles [4][5][6][7][8].…”