We haven’t seen this in a mammal! Rewrite the textbooks!

Textbooks have a lot to answer for.

Textbooks are not the compilation of all knowledge in a field. They are simplified summaries created to teach students new to a field the general lay of the land.

People forget this. Cranks get obsessed with advancing their pet theories by attacking “textbook examples,” because they think the textbook example is all the evidence we have. “If I can show there’s something wrong with the peppered moth example of natural selection, I’ll prove evolution is fake!”

Admittedly, legitimate researchers say, “One day, this will be in all the textbooks!” sometimes, too. It can look self-aggrandizing and egotistical, though.

So this press release titled

Rewrite the textbooks

Findings challenge conventional wisdom of how neurons operate

annoyed me and set off my bullshit filter. My annoyance got worse with the first sentence, and continued increasing as I read the press release.

The good news is that the paper is nowhere near as bombastic as the press release. It is a very good paper. It acknowledges the state of the art in the field and does not present itself as revolutionary. The experiments are technically proficient. And the findings are intriguing.

Let’s compare what the press release says and what the paper says.

Press release:

(T)he basic functional concept is that synapses transmit electrical signals to the dendrites and cell body (input), and axons carry signals away (output).

Paper (my emphasis):

There are exceptions to this, including neurons that lack dendrites or an axon, as well as action potentials propagating from the axon into dendrite. In invertebrates, action potentials can originate in multiple sites, including axon terminals.

What the press release is putting first as the big new finding is not new. It. Just. Is. Not. And the paper’s authors know this and say so in the paper.

In the press release, though, one of the authors, Nelson Spruston, changes his tune:

“Signals can travel from the end of the axon toward the cell body, when it typically is the other way around. We were amazed to see this.”

A neuroscientist amazed by this is either playing to the microphone, or is admitting that he started the project with an ignorance of the diversity of neurobiology. There is certainly no shame in the latter; many neuroscientists concentrate so deeply on one system, they aren’t aware of what else is out there. But playing up, “The signal! It goes backwards! Up the axon!” as something amazing, new, and borderline revolutionary after you’ve admitted in the paper that it happens in other systems is overdoing it.

If I were to rewrite textbooks on this point, it would be to add, “Invertebrates have nervous systems that often work differently than mammals.” Most neuroscience textbooks are far too fixated on humans, mammals, and vertebrates, in that order. If it weren’t for Hodgkin and Huxley’s work on action potentials in squid giant axon, you might have no idea that invertebrates existed.

Press release:

A deeper understanding of how a normal neuron works is critical to scientists who study neurological diseases, such as epilepsy, autism, Alzheimer’s disease and schizophrenia. ...

This unique neuronal function might be relevant to normal process, such as memory, but it also could be relevant to disease.

Paper:

Consolidating these results suggests the existence of a previously unknown operational mode for some mammalian neurons. ... The mechanisms responsible for all aspects of this new operational mode are unknown and elucidating them will require extensive work.

These guys care about how cells work. There’s no mention of medical applications anywhere. (They do mention epilepsy, because neurons in animals with epileptic-like conditions do odd things.)

The press release is making empty promises. “What are the practical applications of this?” is a science journalism cliché ranking up there close to “He said, she said.”

Press release:

“It”s very unusual to think that a neuron could fire continually without stimuli,” Spruston said.

My first reaction was, “Hello! Spruston! They’re called pacemaker potentials and plateau potentials! Both well described in lots of neural circuits!” A pacemaker potential occurs in a neuron that fires over and over again, spontaneously. A plateau potential occurs when a short input causes sustained firing that is much longer than the input; input less than a second could trigger firing for tens of seconds or even minutes.

Paper:

What Sheffield, Spruston and company have found is something that resembles plateau potentials, but is operating on a different timescale. Plateau potentials are triggered by very distinct, short inputs that depolarize the neuron. The neurons in this paper are getting “set off” by long trains of many events. You need hundreds of potentials (small bottom trace) over many seconds to “set off” these long sets of spikes in response in the downstream cell.

That is different and noteworthy and something I haven’t see quite seen before.

And it’s happening in the axon. Potentials starting in the axon isn’t new, and long periods of firing without stimuli isn’t new, but the combination of those two, plus the long time frame of the trigger (the most truly new and interesting thing in the paper, in my estimation) makes for intriguing combination.

Press release:

Their studies of individual neurons (from the hippocampus and neocortex of mice) led to experiments with multiple neurons, which resulted in perhaps the biggest surprise of all. The researchers found that one axon can talk to another.

“But... but... but... Axons interacting with axons isn’t new. I learned the term ‘axoaxonic synapse’ from a diagram in a textbook showing two axons connected to each other. Presynaptic inhibition is two axons talking to each other, and Dudel and Kuffler described that in the 1960s.”

Paper: All of the experiments I described above have involved single cells responding to the experimenter. When they were recording from two neurons, they found that occasionally (3 of 19 pairs), when one cell was “set off” into a bout of sustained firing, the partner cell would also go into a long set of sustained firing. This suggests this phenomenon could be a substantial part of the network in this region of the brain (hippocampus).

Finally, Sheffield and colleagues admit they don’t know how these cells are able to generate persistent firing. (This will probably keep this finding out of textbooks until they get the mechanism down. Phenomena without mechanisms are curiosities. Textbooks thrive on neat, complete stories.) Putting on chemical that block gap junctions prevents this sustained firing. But it’s still up in the air as to what gap junctions, where, between what cell, might be involved.

Press release:

Spruston credits the discovery of the persistent firing in normal individual neurons to the astute observation of Mark Sheffield, a graduate student in his lab.

I say this seriously, with no irony intended: That was a classy thing to say, Dr. Spruston, and good on you. Grad students do not get anywhere near enough credit for being the drivers of discovery that we know they are.

Recently, John Rennie asked science journalists to image what would happen if they didn’t write about papers the same week they were released. This press release was written two months after the pre-print of the paper was published online.

So a cooling off period did not appear to help in this case. The press release is breathless and hyped and oversells a paper that is very admirable and interesting. This paper is like a top notch remix of a song: there’s more old stuff than new material, but the combination is cool and worth listening to.

References

Sheffield M, Best T, Mensh B, Kath W, Spruston N (2010). Slow integration leads to persistent action potential firing in distal axons of coupled interneurons. Nature Neuroscience 14(2): 200-207. DOI: 10.1038/nn.2728

Dudel J, Kuffler SW. 1961. Presynaptic inhibition at the crayfish neuromuscular junction. Journal of Physiology 155(3): 543–562. PDF

Hat tip to GertyZ for finding me a PDF of the paper so I could compare it to the press release!

Photo by punkrockscience on Flickr; used under a Creative Commons license,