Heterogeneity of voltage gated sodium current density between neurons decorrelates spiking and suppresses network synchronization in Scn1b null mouse models
Scientific Reports(2023)
Abstract
Voltage gated sodium channels (VGSCs) are required for action potential initiation and propagation in mammalian neurons. As with other ion channel families, VGSC density varies between neurons. Importantly, sodium current ( I Na ) density variability is reduced in pyramidal neurons of Scn1b null mice . Scn1b encodes the VGSC β1/ β1B subunits, which regulate channel expression, trafficking, and voltage dependent properties. Here, we investigate how variable I Na density in cortical layer 6 and subicular pyramidal neurons affects spike patterning and network synchronization. Constitutive or inducible Scn1b deletion enhances spike timing correlations between pyramidal neurons in response to fluctuating stimuli and impairs spike-triggered average current pattern diversity while preserving spike reliability. Inhibiting I Na with a low concentration of tetrodotoxin similarly alters patterning without impairing reliability, with modest effects on firing rate. Computational modeling shows that broad I Na density ranges confer a similarly broad spectrum of spike patterning in response to fluctuating synaptic conductances. Network coupling of neurons with high I Na density variability displaces the coupling requirements for synchronization and broadens the dynamic range of activity when varying synaptic strength and network topology. Our results show that I Na heterogeneity between neurons potently regulates spike pattern diversity and network synchronization, expanding VGSC roles in the nervous system.
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Key words
neurons,scn1b,null mouse models,current density,sodium
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