[Neuroscience] Re: Gap Junctions and Epilepsy

jonesmat via neur-sci%40net.bio.net (by jonesmat from physiology.wisc.edu)
Tue Jul 31 01:09:22 EST 2007


On Jul 18, 6:52 am, r norman <r_s_norman from _comcast.net> wrote:

>
> Another big win for press release excesses!
>
>
>Excitatory electrical coupling in groups of cells that
> fire rhythmically is far from a novel type of brain communication and
> has long been known and studied.

I agree completely. Most things said in press releases should be
immediately ignored, and with extreme prejudice.

But to fill in the backstory here, why these studies are noteworthy is
that a) there are really very few examples of gap junction coupling in
mammalian CNS between mature excitatory neurons, b) Roger Traub
proposed this pyramidal-pyramidal axon-axon coupling several years ago
based on electrophysiological data, c) this story fit in nicely with
Traub's modeling of hippocampal function (which is famous and
important), and with explaining some of the in vivo EEG and single-
unit data, d) but the story did not attain widespread acceptance
because part of it had to do with the special location of these
particular junctions between axon initial segments, which is a
difficult thing to demonstrate from purely electrical data. So the
novel thing reported in the press release (haven't read the paper
itself) is that there are apparently now EM data confirming the
original predictions in some detail. So it's a success story for
anatomical predictions based on electrophysiological data (and here, I
can't resist pointing out that Hodgkin and Huxley predicted that K
channels would have four subunits based solely on voltage-clamp data
from native neurons, and before the terms "subunit" or even "ion
channel" had been established in this context - being just a dumb
patch clamper, i love it when that happens!).

I think that this new evidence, if it is right, forces *some*
rethinking of our mental picture of, say, hippocampal pyramidal
neurons and their function (and, yes, maybe this will explain
epilepsy, but that's jumping the gun to put it mildly). But we're
scientists, right? Presumably we're all in the business of rethinking
things we thought we already knew. We already knew that lots of other
neurons (e.g., most recently in the press: GABAergic interneurons)
were gap junction-coupled in very specific ways. We also already knew
that pyramidal cells (especially CA3 pyramidal cells) were directly
coupled by recurrent excitatory chemical synapses. So this is not
novel in the sense of a fundamentally new kind of coupling. It's
really something we already knew about, in a place we weren't
expecting to find it. But in hindsight, gap junction coupling between
cells of the same class appears now to be the rule, rather than the
exception. So the deeper question is: "why weren't we expecting to
find it in pyramidal cells?". Traub should be praised for (among many
other things) allowing his data to decide what he expected, rather
than the other way around.

Cheers,

Matt







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