P233 Extracellular K+ hotspots regulate synaptic integration in the dendrites of pyramidal neurons
Malthe S. Nordentoft1, Naoya Takahashi2, Mathias S. Heltberg1, Mogens H. Jensen1, Rune N. Rasmussen3,Athanasia Papoutsi*4
1 Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark
2 Interdisciplinary Institute for Neuroscience, University of Bordeaux, Bordeaux, France
3 Center for Translational Neuromedicine, University of Copenhagen, Copenhagen, Denmark
4 Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology—Hellas, Crete, Greece
*Email:papoutsi@imbb.forth.gr
Introduction
Throughoutthenervoussystem,neuronal activity and ionic changes in the extracellular environment are bidirectionally linked. Changesintheconcentration of extracellularK+ions ([K+]o)are particularly intriguing due to its pivotal role in shaping neuronal excitability and its activity- and state-dependent fluctuation [1]. At the synaptic level, [K+]ochanges arise mainly from the activation of NMDA receptors and are highly localized [2]. Despite this experimental evidence, local, activity-dependent [K+]ochanges have not been considered an integral part of neuronal signaling. In this work [3], we hypothesize that [K+]ochanges form “K+hotspots” that locally regulate the active dendritic properties and shape sensory processing.
Methods
We focus on the organization of orientation-tuned synapses on dendrites of visual cortex pyramidal neurons [4], as we have previously shown that visual cortex responses are dynamically regulated by [K+]oand brain states [1]. We first analytically investigate the spatial diffusion of K+ions, to evaluate the creation of“K+hotspots”. Following, by treating orientation-tuned inputs to dendritic segments as statistical ensembles, we infer the expected changes in Δ[K+]oand the correspondingEK+shifts. Finally, using biophysically realistic models of a point dendrite anda morphologically detailed neuron, weevaluate theeffect of the differentEK+shifts in thedendritic spike propertiesand the neuronal output.
Results
Our statistical approach identified the expectedEK+shifts under different extracellular space sizes, intracellularK+concentration changes, and presented stimuli. Importantly, dendritic segments receiving similarly-tuned inputs attain substantially higher [K+]oandEK+shifts, with theEK+shifts being within the 6-18mV range. In the point dendrite model, this range ofEK+shifts broadens dendritic spikes and increases dendritic spike probability. Finally, in the morphologically detailed neuron models, we show that the local activity-dependent[K+]oincrease andEK+shifts in dendrites enhance the effectiveness of distal synaptic inputs to cause feature-tuned firing of neurons, without comprising feature selectivity.
Discussion
In this work [3] we show that dendrites receiving similarly-tuned inputs support activity-dependent, local changes in[K+]o, forming “K+hotspots”. These hotspots depolarizeEK+and increase the reliability and duration of dendritic spikes. These effects act as a volume knob of dendritic input, promoting gain amplification of neuronal output without affecting the feature selectivity. Overall, compared to long-term plasticity mechanisms, “K+hotspots” are transient, closely follow the overall dendritic activity levels and selectively boost integration of synaptic inputs with minimum usage of resources. Our results therefore suggest a prominent and previously overlooked role of [K+]ochanges.
Acknowledgements
We thank Akihiro Matsumoto, Alessandra Lucchetti, Eva Maria Meier Carlsen, Ioannis Matthaiakakis, and Stamatios Aliprantis for discussions and comments on this work.
References
1.https://doi.org/10.1016/j.celrep.2019.06.082
2.https://doi.org/10.1016/j.celrep.2013.10.026
3.https://doi.org/10.1371/journal.pbio.3002935*PLoS Biology Issue Image | Vol. 22(12) January 2025
4.https://doi.org/10.1038/s41467-019-13029-0
