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Matt Jones jonesmat at ohsu.edu
Fri Feb 19 14:32:45 EST 1999

In article <36CC846B.A870B48F at microsoft.com> Bill Gates,
bgates at microsoft.com writes:
>    This group doesn't seem to have much traffic, but it could just be
>my server.  I have a
>question.  In my neurobiology class, we were discussing the abundance of
>neurotransmitters; and my prof asked us for guesses of the cause.  She
>put me on the spot, so I suggested that perhaps certain regions of the
>brain primarily respond to certain transmitters, and other regions are
>more responsive to another subset.  Thus, it would be possible for the
>brain to regulate activity in various regions by simply controlling the
>concentration of various transmitters.
>    My prof didn't buy this explanation (and I don't entirely blame her,
>since I pretty much made it up from my meager knowledge of
>neurotransmitters), and instead suggested that the abundance is to
>facilitate "fine tuning" of the transmitter action.  She further
>suggested that part of the abundance is due to evolutionary "garbage".
>I don't entirely buy her explanation.  Would anybody be able to shed
>some light on this issue?

There is truth in both of your answers. There are definitely parts of the
brain that have receptors for certain transmitters that other regions
don't. But these "regions" are usually not divided up into large discrete
chunks. Instead, a particular region has several different subtypes of
neurons in it, with each subtype having its own specific complement of
receptors. For example, in hippocampus, there are a couple of classes of
excitatory neurons and many classes of inhibitory neurons. Most of the
excitatory neurons respond to glutamate and GABA, but not so much to
opiods. Of the inhibitory neurons, many respond to glutamate, GABA,
serotonin, opiods, norepinephrine, etc (this explanation is a little
simplistic, but has a core of truth). Different classes of inhibitory
neurons respond differently because they express different receptors, or
receptors in different proportions. They also are targeted specifically
by different transmitter systems. Some get synapses where serotonin is
released, other get synapses where norepinephrine is released, etc. You
were right in the sense that the brain can regulate the function of
different subsets of cells by controlling how much (and how often)
different transmitters are released. But this control is usually spread
diffusely through a tissue, rather than operating similarly on all the
cells in a whole area.

And your prof was right that the abundance of _different_ types of
neurotransmitters is probably for fine tuning purposes. Most of the
synapses in the brain use either glutamate or GABA (the main excitatory
and inhibitory transmitters). These do all the grunt work, in that they
either promote or inhibit firing. The actions of dopamine, serotonin, and
all the rest (which all put together are released at only about 10% of
synapses), modulate either the neuron's membrane potential, membrane
resistance, the function of other receptors/ion channels, or metabolic
processes to fine tune the cell and (sometimes subtly) alter its response
to the more prevalent excitatory or inhibitory inputs.

As for the "evolutionary garbage" idea, I think what your prof may have
meant is that there's always an ongoing process of mutation and selection
among both neurotransmitters and receptors. Evolution is always trying
out new structures by accident, and some of these turn out to be useful.
So you may end up with ten different (but closely related) peptides
acting on twenty different (but closely related) receptors, where they
are all doing the same job (for example, causing the opening of potassium
channels). All this is "garbage" in the sense that at the beginning, you
already had one peptide and one receptor capable of opening potassium
channels, so why make more?  The standard argument (a favorite of people
who are in the business of identifying and cloning new receptors) is that
all these new ones differ from each other in very subtle ways that allow
for more versatility in fine tuning. So in that sense, they're not
garbage, they're highly evolved, highly specialized systems for getting
the most diversity in the range of neural responses. Maybe this is right.
But maybe it was just evolutionarily cheaper to leave all these extra
proteins lying around than it would be to get rid of them once they're

Matt Jones

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