IUBio

37.7 million artificial neurons

Matt Jones jonesmat at ohsu.edu
Wed Jan 27 15:40:19 EST 1999


In article <36ADF792.64C8EC44 at idi.ntnu.no> Gerthory Toussaint,
toussain at idi.ntnu.no writes:
>Hello All,
>
>    I would like to ask you a question about the release of
>neurotransmitter. Does it possible for a neuron to release several
>different type a neurotransmitter a the same time ? I read that neurons
>have several transmitter. Can someone tell me if this mechanism is based on
>the frequency of the input signal/the area of the brain which is excited or
>both ?
>
>    By the way, is it possible for a neuron to distinguish a pain signal ?
>(does they release a special neurotransmitter ?)
>
>Thank you very much for any answer which can help me.
>

Yes, this can happen (contrary to what I, Frank, and almost everyone else
was taught in grad school).

There are two kinds of mechanisms.  First, synaptic terminals often have
two types of synaptic vesicles. Small, clear-core vesicles (CCVs) contain
the common neurotransmitters, glutamate, ACh, GABA etc. Usually, a given
neuron will only release ONE of these transmitters. I'm not aware of a
clear demonstration of a neuron releasing both glutamate and GABA, or ACh
and glutamate, and so on (but see below). An exception to this might be
ATP, which is in most vesicles, and may be coreleased with other
transmitters. But whether the ATP acts as a transmitter of course depends
on whether there are receptors for it at those synapses. Anyway, there
are also large, dense-core vesicles (DCVs), that often contain peptide
neurotransmitters (they are "dense" in the optical sense, because they
contain big bulky molecules). These can exist within the same terminals
as the CCVs, but are usually located further back from the release sites,
are possibly attached to distinct membrane trafficking components, and
thus may require different stimulus parameters to be released (i.e.,
bursts or high frequency trains). I think most of the work on this has
been done in invertebrates like Aplysia and leech. Try a web search for
"P. Lloyd AND Aplysia" for research papers and further references to this
type of corelease mechanism.

Second, and even more heretically, is a mechanism in which two similar
neurotransmitters can be packaged into the SAME CCVs, and released
simultaneously (during the same vesicle fusion event, so the time scale
for "simultaneously" here is measured in microseconds). This was recently
demonstrated by Jonas, Bischofberger and Sandkuhler (see abstract below).
The transmitters involved are glycine and GABA, both inhibitory
transmitters that act on very similar receptors. Glycine and GABA are
sufficiently similar molecules that probably a single vesicular amino
acid transporter is responsible for packaging them both into the
vesicles. However, it's also probably not an accident that this happens
at the synapses studied, because the postsynaptic neurons also place both
glycine and GABA receptors at these synapses. These receptors
discriminate very well between the two transmitters, and also have
somewhat different kinetics. So it's possible that here, the corelease,
or the differential release, serves a useful role in setting the dynamics
of the neural circuit, owing to the ability to modulate the shape of the
inhibitory synaptic currents depending on the ratio of GABA to glycine
released. Cool stuff.

Cheers,

Matt Jones




Corelease of two fast neurotransmitters at a central synapse.

Jonas P, Bischofberger J, Sandkuhler J

Physiologisches Institut der Universitat Freiburg, D-79104 Freiburg,
Germany. jonasp at ruf.uni-freiburg.de 

It is widely accepted that individual neurons in the central nervous
system release only a single fast transmitter. The possibility of
corelease of fast neurotransmitters was examined by making paired
recordings from synaptically connected neurons in spinal cord slices.
Unitary inhibitory postsynaptic currents generated at
interneuron-motoneuron synapses consisted of a strychnine-sensitive,
glycine
receptor-mediated component and a bicuculline-sensitive,
gamma-aminobutyric acid (GABA)A receptor-mediated component. These
results indicate that spinal interneurons release both glycine and GABA
to activate functionally distinct receptors in their postsynaptic
target cells. A subset of miniature synaptic currents also showed both
components, consistent with corelease from individual synaptic
vesicles.



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