to their activation near the resting membrane potential, as well as their fast recovery from inactivation, they are able to generate low-threshold spikes, which results in a burst of action potentials. T-type channels play a secondary pacemaker role in neurons that have resting membrane potential between -90 and -70 mV as they have an important role in the genesis of burst firing. An excitatory postsynaptic potential (EPSP) opens the channels, thus generating a LTS. The LTS triggers Na+-dependent action potentials and activates high-voltage activated calcium channels. Low-threshold spikes generate burst firing Evidence for low-threshold calcium current was first described in neurons of the inferior olivary nucleus (1981). This nucleus generates synchronous rhythmic activity, which under certain conditions is manifested as a tremor. Low-threshold calcium spikes have been described in neurons from a variety of brain nuclei, including the thalamic relay, medial pontine reticular formation, lateral habenula, septum, deep cerebellar nuclei, CA1-CA3 of the hippocampus, association cortex, paraventricular and preoptic nuclei of the hypothalamus, dorsal raphe, globus pallidus, striatum, and subthalamic nucleus. Thalamic relay cells show two types of responses. One response mode is a relay or tonic mode, in which the cell is depolarized and LTS are inactivated. This leads to tonic firing of action potentials. The second response is a burst mode, in which the cell is hyperpolarized and typically responds with LTS and their associated bursts of action potentials. In general, LTS cannot be triggered by depolarization of the neuron from the resting membrane potential. LTS is observed after a hyperpolarizing pulse is delivered to the neuronal cell, which is called "deinactivation" and is a result of channels recovering from inactivation. LTS are often triggered after an inhibitory postsynaptic potential (IPSP) due to the fast recovery of T-type calcium channels during the IPSP and their opening, as there is a return to resting membrane potential. There is a strong correlation between LTS amplitude and the number of action potentials that result from a LTS. There is much more depolarization of T channels near the dendritic location of activated receptors than at the soma. The activation of either metabotropic glutamate or muscarinic receptors results in a hyperpolarizing shift in the relationship between LTS amplitude and the initial potential of the membrane. This affects the maximum LTS amplitude. This means that there is a dependency between the LTS amplitude and voltage, and therefore the resulting number of action potentials generated.