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[Neuroscience] Re: Electrophysiology: monosynaptic vs heterosynaptic transmission.

r norman NotMyRealEmail at _comcast.net
Wed Feb 22 23:46:09 EST 2006


On Wed, 22 Feb 2006 19:29:36 +0100, SJM Guzman
<jose.guzman at medizin-uni-leipzig.de> wrote:

>Hi R. Norman:
>
>Your explanation was fabulous. I was kind of confuse regarding the 
>terminology homosynaptic/monosynpatic. Now is clear to me. Again thank 
>you very much.
>
>Regarding the field potential question.... To access the monosynaptic 
>component, some laboratories analyze EPSP slopes using the least-squares 
>regression. Why not simply to analyze the amplitude?
>
>Here some examples of publications...
>
>"For EPSP analysis, The initial rising slope was measured, (1 msec 
>period form its onset, in milivolts per millisencond), which contains 
>only a monosynaptic component )..."
>
>"To minimize the contribution of voltage-dependent conductances, initial 
>slopes of EPSPs were calculated..."
>
>I would appreciate some literature about it. I miss some about PSC/Ps, 
>because traditional electrophysiological books (i.e Hille, Neher & 
>Sakmann), don't tell much about it.
>
>Thank you very much again!

It is very easy to find a lot of papers that refer to PSP slopes,
whether measured as field potentials or with intracellular electrodes.
However I have not been able to find any web sites that explain just
why this measurement is used.

Here is my interpretation, but this is really conjecture on my part.
Somebody jump in here if it is wrong!

The really proper direct measure of synaptic response is channel
opening.  However that can't be seen directly.  Channel opening is
directly related to membrane conductance.  However measuring
conductance is often technically impossible, is disruptive to normal
cell function, and averages conductance changes over too large an area
of membrane.  The next most direct response is synaptic current.  If
the membrane is voltage clamped to a fixed value, the current through
any one synapse will be directly proportional to the channel openings
(conductance changes) assuming the reversal potential (ion
concentrations) do not change significantly. The most indirect
response is  synaptic potential itself.  The amplitude of the psp will
depend greatly on all sorts of disturbing influences going on in the
cell.

So measuring synaptic current is a far better way of measuring
synaptic function than measuring synaptic potential. Unfortunately,
directly measuring current usually means doing a voltage clamp which
is often technically impossible.  However, the slope of the rising
phase of the psp is a very good measure of synaptic current.  During
this time, the current through the synaptic channels completes its
closed loop by flowing across the membrane in the form of capacitative
current which obeys the law I = C dV/dt.  Since C is essentially
constant, dV/dt is a direct measure of I.  The falling slope is very
different since the synaptic channels are then closed and that slope
depends on the cable properties of the cell, especially the way that
the current distributes longitudinally down the dendrites and the
membrane time constant.  Note: the "effective time constant" during
the rising phase of the psp is very different from that during the
falling phase because of the changes in membrane conductance.

I don't know just where all this is explained.  I do know that Hodgkin
and Katz (I think it was their 1949 paper, I don't have my texts with
me on vacation) used the slope of the rising phase of the action
potential as a far better measurement of the sodium current inrush
than the actual amplitude of the action potential.  They explained why
in an appendix to the paper.  Just as the action potential is caused
by sodium currents flowing through open sodium channels, the synaptic
potential is caused by ion currents flowing through open synaptic
channels and the same logic applies.

If I recall correctly (again, I don't have the books with me) Neher
and Sakmann concentrate (as to be expected) on patch clamp data and I
seem to recall Hille doing similarly.  Many texts go into the
molecular machinery of ion channels and receptor binding and so on but
short change the biophysics of the electrical details.




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