Low-threshold spikes (LTS) refer to membrane depolarizations by the T-type calcium channel. LTS occur at low, negative, membrane depolarizations. They often follow a membrane hyperpolarization, which can be the result of decreased excitability or increased inhibition. LTS result in the neuron reaching the threshold for an action potential. LTS is a large depolarization due to an increase in Ca2+ conductance, so LTS is mediated by calcium (Ca2+) conductance. The spike is typically crowned by a burst of two to seven action potentials, which is known as a low-threshold burst. LTS are voltage dependent and are inactivated if the cell's resting membrane potential is more depolarized than −60mV. LTS are deinactivated, or recover from inactivation, if the cell is hyperpolarized and can be activated by depolarizing inputs, such as excitatory postsynaptic potentials (EPSP). LTS were discovered by Rodolfo Llinás and coworkers in the 1980s. Physiology Rhythmicity Rhythmogenesis in a neuron is due to an instability associated with the resting potential. Such instability can be attributed to properties of low-threshold calcium currents. The current is activated at around −60 mV, making it able to generate a low-threshold spike at or near the resting potential. In a somewhat recent finding, cells maintained at a hyperpolarized level have been shown to exhibit intrinsic rhythmicity, resulting in spontaneous oscillatory behavior due to Ca2+ driven depolarizations. As a result, one or more short bursts of spikes occur, followed by hyperpolarization, and then repolarization before the next burst. LTS kinetics A study done by Gutierrez et al. examined the kinetics behind low-threshold spikes to better understand their significance towards normal functions of the brain. It has been determined experimentally that four ionic currents contribute to low-threshold spikes, generating three distinct phases after hyperpolarization. Transient outward K+ currents following action potentials can cause hyperpolarization, allowing for low-threshold spikes. An initial ohmic leakage current composed of K+ and Na+ ions characterizes the first phase. This is followed by a hyperpolarization-activated "sag" current that contributes to slowly depolarizing the membrane potential. An inward Ca2+ current through T-type calcium channels is the last phase, and the main current responsible for the large transient depolarization. This overrides the other currents once T-type channels are activated. The other currents primarily affect the activation of the LTS. T-type calcium channel The T-type calcium channel is found in neurons throughout the brain. These channels produce particularly large currents in thalamic, septal, and sensory neurons. Due