The Global Spike: Conserved Dendritic Properties Enable Unique Ca2+ Spike Generation in Low-Threshold Spiking Neurons

Low-threshold Ca²⁺ spikes (LTS) are an indispensible signaling mechanism for neurons in areas including the cortex, cerebellum, basal ganglia, and thalamus. They have critical physiological roles and have been strongly associated with disorders including epilepsy, Parkinson's disease, and schizophrenia. However, although dendritic T-type Ca²⁺ channels have been implicated in LTS generation, because the properties of low-threshold spiking neuron dendrites are unknown, the precise mechanism has remained elusive. Here, combining data from fluorescence-targeted dendritic recordings and Ca²⁺ imaging from low-threshold spiking cells in rat brain slices with computational modeling, the cellular mechanism responsible for LTS generation is established. Our data demonstrate that key somatodendritic electrical conduction properties are highly conserved between glutamatergic thalamocortical neurons and GABAergic thalamic reticular nucleus neurons and that these properties are critical for LTS generation. In particular, the efficiency of soma to dendrite voltage transfer is highly asymmetric in low-threshold spiking cells, and in the somatofugal direction, these neurons are particularly electrotonically compact. Our data demonstrate that LTS have remarkably similar amplitudes and occur synchronously throughout the dendritic tree. In fact, these Ca²⁺ spikes cannot occur locally in any part of the cell, and hence we reveal that LTS are generated by a unique whole-cell mechanism that means they always occur as spatially global spikes. This all-or-none, global electrical and biochemical signaling mechanism clearly distinguishes LTS from other signals, including backpropagating action potentials and dendritic Ca²⁺/NMDA spikes, and has important consequences for dendritic function in low-threshold spiking neurons.

SIGNIFICANCE STATEMENT Low-threshold Ca²⁺ spikes (LTS) are critical for important physiological processes, including generation of sleep-related oscillations, and are implicated in disorders including epilepsy, Parkinson's disease, and schizophrenia. However, the mechanism underlying LTS generation in neurons, which is thought to involve dendritic T-type Ca²⁺ channels, has remained elusive due to a lack of knowledge of the dendritic properties of low-threshold spiking cells. Combining dendritic recordings, two-photon Ca²⁺ imaging, and computational modeling, this study reveals that dendritic properties are highly conserved between two prominent low-threshold spiking neurons and that these properties underpin a whole-cell somatodendritic spike generation mechanism that makes the LTS a unique global electrical and biochemical signal in neurons.

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