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bioRxiv · 10.1101/2022.03.15.484426

Glocal dendritic spikes: variation in branch activity during dendritic spiking indicates multiple functional units in the pyramidal neuron apical tuft

Geron, E.
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Abstract

There is a lively debate on how many functional units exist within the dendritic tree of pyramidal neurons (PNs). The classical view that the PNs dendritic tree comprises several computational units 1-4 was challenged by recent in-vivo studies that identified mainly widespread dendritic spikes 5-10, suggesting a low degree of dendritic compartmentalization. We reasoned that global spikes do not rule out dendritic compartmentalization if these spikes contain a high variation in branch activity. Therefore, we turned to image Ca2+ activity in many apical dendrites from individual layer (L) 5 PNs of the primary motor cortex (M1). For proper dendritic morphology and Ca2+ activity analysis, we used mice with sparse double labeling of PNs with a structural marker (tdTomato) and a GCaMP6s probe. We first collected data for complete registration of the apical tuft dendritic structure. We then used 3D two-photon microscopy to image Ca2+ activity within these tufts during treadmill running. Using these, we imaged up to 30 apical branches from individual L5 PNs, including branches separated by as many as 11 bifurcations and more than 1000 {micro}m of intracellular distance. We found that local spikes were rare, but global spikes often displayed heterogeneous Ca2+ elevation across branches, giving rise to an activity pattern across the tuft. This spiking pattern was dynamic and according to unsupervised hierarchical cluster analysis, fitted to 2-6 distinct patterns, even over short imaging periods. Taken together, we find a considerable variation in branch activity within and between global dendritic spikes, supporting multiple dendritic functional units. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=83 SRC="FIGDIR/small/484426v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@103ceeaorg.highwire.dtl.DTLVardef@1058a19org.highwire.dtl.DTLVardef@ad7c24org.highwire.dtl.DTLVardef@1b13d94_HPS_FORMAT_FIGEXP M_FIG C_FIG We detected three main spike types. Local spikes were evident in a minority of the branches and had low amplitude. Contrastingly, global spikes often displayed homogeneous levels of branch activity and were the strongest and most prolonged spikes. An intermediate pattern was the "glocal spike," where a global spike exhibited heterogeneous branch activity. Spikes with heterogeneous Ca2+ elevation across branches constituted at least a quarter of all spikes. In the social sciences, the term "glocalization" refers to global phenomena that are adjusted locally, such as food items sold worldwide but attuned to local tastes 11. Influenced by that, we refer to global spikes with heterogeneous branch activity as "glocal spikes."

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Geron, E.. 2022-03-18. Glocal dendritic spikes: variation in branch activity during dendritic spiking indicates multiple functional units in the pyramidal neuron apical tuft. https://doi.org/10.1101/2022.03.15.484426

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