Single-neuron mechanical perturbation evokes calcium plateaus that excite and modulate the network

Mechanical stimulation is a promising means to non-invasively excite and modulate neuronal networks with a high spatial resolution. Despite the thorough characterization of the initiation mechanism, whether or how mechanical responses disperse into non-target areas remains to be discovered. Our in vitro study demonstrates that a single-neuron deformation evokes responses that propagate to about a third of the untouched neighbors. The responses develop via calcium influx through mechanosensitive channels and regeneratively propagate through the neuronal ensemble via gap junctions. Although independent of action potentials and synapses, mechanical responses reliably evoke membrane depolarizations capable of inducing action potentials both in the target and neighbors. Finally, we show that mechanical stimulation transiently potentiates the responding assembly for further inputs, as both gain and excitability are transiently increased exclusively in neurons that respond to a neighbor's mechanical stimulation. The findings indicate a biological component affecting the spatial resolution of mechanostimulation and point to a cross-talk in broad-network mechanical stimulations. Since giga-seal formation in patch-clamp produces a similar mechanical stimulus on the neuron, our findings inform which neuroscientific questions could be reliably tackled with patch-clamp and what recovery post-gigaseal formation is necessary.