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Determination of Synaptic Type ?

Paul Bush paul at phy.ucsf.edu
Tue Feb 13 16:11:33 EST 1996

In article <chimento-0702961005420001 at maculaiv.arc.nasa.gov>, chimento at neuron.arc.nasa.gov (Thomas Chimento) writes:
|> In article <4f5lji$kes at itssrv1.ucsf.edu>, paul at phy.ucsf.edu (Paul Bush) wrote:
|> > In article <4eq6fn$2i6 at helios.herts.ac.uk>, AliStair G Rust
|> <a.g.rust at herts.ac.uk> writes:
|> > |> However, how is the type of synapse determined ?  I've not found anything
|> > |> specific in the literature I've read so I've got a few questions.
|> > |> > 
|> > Type is determined by the presynaptic cell. Excitatory cells (in the
|> cortex this
|> > means spiny cells) send out axons which always make excitatory synapses on the
|> > neurons they contact. Similarly, inhibitory cells (smooth or sparsely spiny
|> > cortical cells) always make the same type of synapse on their postsynaptic
|> > targets. Note that while inhibitory neurons will always release GABA, the
|> > inhibitory cortical neurotransmitter, the effect on the postsynaptic cell
|> > (inhibitory or excitatory) depends on its membrane potential at the time.
|> > 
|> > Kandel means that we can infer whether the synapse is excitatory
|> > or inhibitory from its position on the postsynaptic cell, not that the site of
|> > synaptic contact developmentally determines the type of synapse. Thus, in
|> > cortex, an axo-axonic synapse is inhibitory, an axo-somatic synapse is
|> inhibitory
|> > if on an excitatory cell and can be either if on an inhibitory cell. An
|> > axo-dendritic synapse can be either excitatory or inhibitory. 
|> > 
|> > Examine the synapse at the EM (electron microscope) level. Inhibitory synapses
|> > are symmetrical, meaning they have an equally dense staining layer on
|> both the 
|> > pre- and post-synaptic side of the synapse, and the presynaptic bouton
|> contains 
|> > flattened, eliptical vesicles (packets of neurotransmitter). Excitatory
|> synapses 
|> > are asymmetrical and have round vesicles. Inhibitory are type II,
|> excitatory are
|> > type I (opposite of what you said).
|> >  
|> > Excitatory/inhibitory is detemined by the presynaptic cell, as above.
|> 'Tuning' of
|> > the densities and types of ion channels on the postsynaptic side
|> probably occurs
|> > in response to electirical activity/usage, but this is most likely just
|> changing
|> > the strength of the synapse and not its sign.
|> > 
|> > Paul
|> I would respectfully submit that the nervous system is not so cleanly
|> arranged. I only
|> wish that looking at synapses with an EM could answer all these questions
|> and that each
|> of the synaptic types were so obvious and simple. There are in the range

I think you need to go back and read what I wrote more carefully. I gave an
introductory account of excitatory and inhibitory synapses with particular
reference to the cortex. I stand by every word that I wrote and challenge you to
prove me wrong. Undoubtedly the brain is more complex than I could convey in one
page, but to attempt to do this would not have helped the initial poster, instead
it would just have confused him. I restricted myself to the intrinsic cortical
synapses (not mentioning cholinergic, monoaminergic, peptides etc) for this

EM identification of synapses: what I wrote was a general rule
(symmetric/asymmetric, flat/round vesicles) used to classify synapses as
inhibitory or excitatory. Do you dispute this? I acknowledge that there are
exceptions to this rule and real experimental data are often not as clean as we
might hope.

|> of dozens of 
|> presynaptic neurotransmitters identified and lately the number of
|> postsynaptic receptor
|> types has gotten even worse. The possible permutations make the whole
|> system depressingly
|> complex. That is one reason there are hundreds of articles published in
|> the patch clamp arena

This is true but does not contradict or invalidate anything I wrote.

|> examining the electrical responses of cells - you cant just look at where
|> they are or even 
|> what they look like and know how they behave. Even excitatory and
|> inhibitory are severe
|> oversimplifications. The magnitude and time course of the responses varies
|> dramatically.

Read what I wrote. Show me where it is incorrect. If you think you cannot make
deductions about whether a cortical synapse is excitatory or inhibitory based on
its location on the postsynaptic cell then you are simply ignorant.

|> The sign of the synapse can indeed change depending on the state of the
|> neuron and what
|> other events are occuring near in time. The original set of questions has

As I stated in my post, GABA (inhibitory neurotransmitter), can sometimes have a
depolarizing effect depending on the postsynptic cell's membrane potential.
Glutamate (exctitory neurotransmitter) will always have an excitatory effect
since its reversal potential is so high (about 0 mV). Do you dispute this? In
what other ways does 'the state of the neuron and what other events are 
occuring near in time' change the sign of the synapse? I await illumination.

|> occupied the entire
|> career of scores of investigators - not a few of whom are at UCSF, Paul.

Thanks for the information. I wondered who all those people were that I kept
bumping into in the corridors.

|> The above information
|> is a good place to start - it covers the introductory Neuroscience text
|> presentation of whats

Exactly what the original poster was asking for, and exactly what I was
attempting to provide. Too bad you thought I was trying to review the entire
field of brain synaptology in one page.

|> what - but if you want to know something about a particular synaptic class
|> in a specific site
|> in the brain of a species of animal - you've got a lot more work to do.

If you mean I didn't provide information about every synaptic class in every site
in the brain of every species of animal, then I guess you're correct. Correct,
but clueless.

|> You could never publish
|> an article in J. Neuroscience or J. Neurophysiology saying you knew the
|> function of a synapse based
|> on what it looked like or where it resided, unless the details had already
|> been worked out with
|> numerous other techniques (Immunohistochemistry, cloning the gene for the
|> receptor, electrophysiology

Again, you need to go back and read what I wrote more carefully, as well as
reading more journal articles. For example, inferring that a symmetrical synapse
on the soma of a cortical pyramidal cell is inhibitory is routine.

|> to name a few). Have fun in your endeavors - youve just begun.

Your condescension is misplaced. I suggest you aquire some patience and learn to
read posts in context.

|> Thomas Chimento                 chimento at neuron.arc.nasa.gov
|>                         Keep it simple, do it right.

			   And practice what you preach.


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