Role of low-voltage-activated calcium current on the firing pattern alterations induced by hypothyroidism in the rat hippocampus

Thyroid hormone deficiency during a critical period of development severely affects cognitive functions, resulting in profound mental retardation. Despite the importance of the disorder, the cellular mechanisms underlying these deficits remain largely unexplored. The aim of this study was to examine the effects of the absence of thyroid hormone on the development of the intrinsic properties of CA1 hippocampal pyramidal cells. These cells are known to exhibit different firing patterns during development, being classified as either regular-spiking or burst-spiking cells. Patch-clamp experiments showed that hypothyroid rats presented a larger number of regular-spiking cells at early postnatal age (P9–11). This difference in firing-pattern distribution disappeared at the pre-weanling age (P17–19), when almost every cell displayed bursting behavior in both control and hypothyroid rats. However, when studied in detail, weanling hypothyroid rats presented a smaller number of spikes per burst than did control animals. One of the major factors behind bursting behavior is sustained depolarization following an action potential. In this study, we show that action potential afterdepolarizations of hypothyroid animals registered shorter half-durations than did controls, a fact which could explain the smaller number of action potentials per burst. Additionally, the afterdepolarizations observed on both hypothyroid and control neurons were highly sensitive to low concentrations of nickel, suggesting that a low-threshold Ca2+ current is key in the generation of spike afterdepolarizations and in the control of the bursting pattern of firing of these neurons. In agreement with this, experiments performed on dissociated hippocampal neurons have shown that this current is significantly depressed in hypothyroid animals. Therefore, we conclude that an alteration of the low-threshold calcium current is the basic factor explaining the differences observed in the firing behavior of hypothyroid animals.

Research Highlights▶Congenital absence of thyroid hormone alters neuronal firing behavior. ▶Congenital hypothyroidism increases input resistance and reduces membrane capacitance. ▶Action potential waveform is altered by the absence of thyroid hormone. ▶Action potential afterdepolarizations of hypothyroid rats are different than controls. ▶Low-threshold Ca2+ current is significantly depressed in hypothyroid animals.