Figure 8: hCaV3.3 R1346H (R/H) variant impairs rebound burst firing in TRN neuron simulations.
From: A rare schizophrenia risk variant of CACNA1I disrupts CaV3.3 channel activity
(a) Simulations of membrane voltage in model TRN neurons responding to hyperpolarizing or depolarizing current injections. Left: WT neuron fires a burst of rebound action potentials following 200 ms negative, hyperpolarizing current injections of different magnitudes (upper) and bursts of action potentials during the depolarizing current injection (lower). Right: Neuron with 72.5% of WT CaV3.3 current density to approximate heterozygosity (50% R/H and 50% WT) does not exhibit rebound bursting following hyperpolarization. (b) Relationship between number of rebound spikes and size of hyperpolarizing current injection for a range of CaV3.3 current densities. Percent of CaV3.3 current relative to WT (black) color coded from green (78%) to red (120%). (c) The number of spikes during positive current injections depends on the magnitude of the current injection (x-axis), but it is only marginally influenced by CaV3.3 density. Black lines represent current density for WT and R/H heterozygous cells, with same color spectrum as in (b), extended to 40% of WT (blue).
