Hoerndli, F. | bioRxiv Science

bioRxiv2024

Axonal mitochondria regulate gentle touch response through control of axonal actin dynamics

Actin in neuronal processes is both stable and dynamic. The origin & functional roles of the different pools of actin is not well understood. We find that mutants that lack mitochondria, ric-7 and mtx-2; miro-1, in neuronal processes also lack dynamic actin. Mitochondria can regulate actin dynamics upto a distance [~]80 m along the neuronal process. Absence of axonal mitochondria and dynamic actin does not markedly alter the Spectrin Membrane Periodic Skeleton (MPS) in touch receptor neurons (TRNs). Restoring mitochondria inTRNs cell autonomously restores dynamic actin in a sod-2 dependent manner. We find that dynamic actin is necessary and sufficient for the localization of gap junction proteins in the TRNs and for the C. elegans gentle touch response. We identify an in vivo mechanism by which axonal mitochondria locally facilitate actin dynamics through reactive oxygen species that we show is necessary for electrical synapses & behaviour.

cell biology↗

bioRxiv2023

Spine apparatus modulates Ca2+ in spines through spatial localization of sources and sinks

Dendritic spines are small protrusions on dendrites in neurons and serve as sites of postsynaptic activity. Some of these spines contain smooth endoplasmic reticulum (SER), and sometimes an even further specialized SER known as the spine apparatus (SA). In this work, we developed a stochastic spatial model to investigate the role of the SER and the SA in modulating Ca2+ dynamics. Using this model, we investigated how ryanodine receptor (RyR) localization, spine membrane geometry, and SER geometry can impact Ca2+ transients in the spine and in the dendrite. Our simulations found that RyR opening is dependent on where it is localized in the SER and on the SER geometry. In order to maximize Ca2+ in the dendrites (for activating clusters of spines and spine-spine communication), a laminar SA was favorable with RyRs localized in the neck region, closer to the dendrite. We also found that the presence of the SER without the laminar structure, coupled with RyR localization at the head, leads to higher Ca2+ presence in the spine. These predictions serve as design principles for understanding how spines with an ER can regulate Ca2+ dynamics differently from spines without ER through a combination of geometry and receptor localization. 1 HighlightsO_LIRyR opening in dendritic spine ER is location dependent and spine geometry dependent. C_LIO_LICa2+ buffers and SERCA can buffer against runaway potentiation of spines even when CICR is activated. C_LIO_LIRyRs located towards the ER neck allow for more Ca2+ to reach the dendrites. C_LIO_LIRyRs located towards the spine head are favorable for increased Ca2+ in spines. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/558941v1_fig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@1a2aa64org.highwire.dtl.DTLVardef@60a7c5org.highwire.dtl.DTLVardef@1a68303org.highwire.dtl.DTLVardef@e3743f_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 1:C_FLOATNO Graphical abstract. Factors governing the dynamics of Ca2+ in dendritic spines include plasma membrane geometry, RyR distribution and ER laminarity. C_FIG

neuroscience↗