In what ways can neurons fire randomly?

Question

When developing a model of a biologically-plausible neural network, it is important to know all the circumstances under which neurons can fire. But, I am limiting this question to random firing. In what ways, if any, can neurons fire randomly, i.e., without (or regardless of) presynaptic input?

I'm looking for something like:

Between 0 and 6 days of age, rat cortical neurons randomly fire at an average rate of once every 30 minutes. The rate decreases to 0 by age 12 days. Reference: here

(That's just an example)

In what ways can neurons fire randomly?

Answer 1

Answering the question in the manner that you are asking for would require quite an exhaustive list. However, a fundamental concept in all of this is having a "leak" channel.

NALCN is the only nonselective channel found in the 24-TM channel family and is equally permeable to Na+, K+, and Cs+. [1]

The majority of the ions transported by the channel are sodium. This slow influx will have the same effect on voltage over a longer period of time as would a rapid influx, a depolarization of the membrane.

NALCN is found in all animals studied, from humans to D. melanogaster, C. elegans, snails, sea urchins, and the placozoan Trichoplax adhaerens.

So, it is likely that this channel is conserved in the evolutionary ladder.

NALCN mutant mice have a severely disrupted respiratory rhythm and die within 24 hours of birth. Brain stem-spinal cord recordings reveal reduced neuronal firing. The TTX- and Cs(+)-resistant background Na(+) leak current is absent in the mutant hippocampal neurons. [2]

This addresses your other question, this leakage makes the membrane voltage more permissive to initiation of rhythmic discharge and other oscillatory behaviors.

As to whether anything fires "randomly", I would say that neurons can fire with a given distribution [3], but this is governed by all the different channels which operate and their conductances (inverse of resistance) rather than just by chance alone. Remember, if a neuron fires randomly, it's not likely to have much effect on a post-synaptic cell unless it's time-locked to a series of other action potentials arriving at the same spot.

[1] Ren, D. (2011). Sodium Leak Channels in Neuronal Excitability and Rhythmic Behaviors. Neuron, 72(6):899-911. http://www.ncbi.nlm.nih.gov/pubmed/22196327

[2] Lu B, Su Y, et al (2007). The neuronal channel NALCN contributes resting sodium permeability and is required for normal respiratory rhythm. Cell, 129(2):371-83. http://www.ncbi.nlm.nih.gov/pubmed/17448995

[3] Webb TJ, Rolls ET, Deco G, Feng J. (2011) Noise in attractor networks in the brain produced by graded firing rate representations. PLoS One, 6(9):e23630. Free PDF

Answer 2

Closely related to random firing:

Neurotransmitter-filled vesicles are released not only en masse when a neuron fires but also individually at random intervals. Nobel laureate Bernard Katz, who studied NMJs, observed:

In the absence of any form of stimulation, the end-plate region of the muscle fibre is not completely at rest, but displays electric activity in the form of discrete, randomly recurring miniature end-plate potentials.

For chemical synapses in general (not just NMJs), such potentials are known as miniature excitatory postsynaptic potentials.

References

• Katz, B. (1970) On the quantal mechanism of neural transmitter release. Nobel lecture.

Answer 3

First, you need to keep in mind that what one would consider "random" might not be "random" for another person. On one extreme, some scientists believe the brain is operating essentially deterministically (thermal/quantum noise is too small), that is, if you know the "precise" state of the brain and its environment, you can predict its future states for a very long time. Regardless of the truth of that statement, neural signals are effectively random due to our lack of knowledge.

Now, you specifically asked if a neuron can make random responses regardless of synaptic input. Yes, it can.

1. There have been many controlled current injections to neurons. For example, in the figure below, repeated trials with exactly same current step show slight differences in the spike trains.

2. Thermal fluctuations of channels can cause spontaneous fluctuations in the membrane potential.

3. There are spontaneously firing neurons (no synaptic input necessary). (See https://biology.stackexchange.com/a/15259/460)

Figure from: Mainen, Z. F. and Sejnowski, T. J. (1995). Reliability of spike timing in neocortical neurons. Science, 268(5216):1503-1506.