Low-threshold spikes

Key takeaways

Low-threshold spikes belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Low-threshold spikes to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Low-threshold spikes from memory before moving on to harder problems.

Reference excerpt

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 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.

LTS is mediated by a Ca2+ conductance When the hyperpolarization of the membrane in these interneurons is maintained at a certain level calcium conductance is reduced, if not completely inactivated. This results in the membrane polarization not being in the right range for single spikes and hence "bursts" result. The LTS therefore is dependent upon the conductance of calcium.

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Worked examples

Example 1 — a first encounter with Low-threshold spikes

Start with the simplest possible case. Write down what Low-threshold spikes claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Low-threshold spikes before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Low-threshold spikes ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Low-threshold spikes

In research: Low-threshold spikes appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Low-threshold spikes in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Low-threshold spikes is common in secondary-school and first-year university syllabi. It links to neighbouring topics Cellular neuroscience, Electrophysiology, so understanding it makes those chapters shorter.
In everyday life: Look for Low-threshold spikes outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Low-threshold spikes in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Low-threshold spikes means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Low-threshold spikes out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Low-threshold spikes in simple terms?

Low-threshold spikes (LTS) refer to membrane depolarizations by the T-type calcium channel. LTS occur at low, negative, membrane depolarizations.

Why does Low-threshold spikes matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Low-threshold spikes?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Low-threshold spikes.