High Resolution Intracellular Recordings?

Matthew Kirkcaldie Matthew.Kirkcaldie at newcastle.edu.au
Wed Sep 3 20:33:21 EST 2003

In article <72de81ae.0309031548.39b66b2d at posting.google.com>,
 y.k.y at lycos.com (yan king yin) wrote:

> I'm trying to find intracellular recordings of the soma of
> in vivo neurons, with *temporal* resolutions in the sub-ms
> range (the finer the better). What I want to see is how the
> spatial and temporal integration actually take place in action.
> Any web page, paper etc...?

There are many such papers, just look for whole-cell patch clamp 
recordings in a lit search engine like PubMed.  They have recordings in 
the picoampere/microsecond range routinely these days.  Generally they 
can be difficult to read for "outsiders" (and I include myself here) 
because they generally refer to inward and outward currents of ions 
under current or voltage clamp conditions, and perform considerable 
restrictions on the constituents of the nutrient bath to isolate certain 
types of events. 

I doubt you could find what you're looking for, which I think is a 
recording showing how EPSPs combine to kick the membrane over threshold.  
Believe it or not, the generation of an action potential is still far 
from understood, despite the known presence of voltage-gated sodium and 
potassium channels in the membrane near the start of the axon.  The work 
of Stuart and Hausser is a recent and fascinating attempt to grapple 
with the dynamics of these events - have a look at their papers.  The 
story they reveal is daunting to say the least - the stereotype of 
dendrites as passive antennas radiating EPSPs to the cell body, which 
then fires if threshold is exceeded, is so over-simplified that it's 
cartoon-like.  Instead, non-linear channel-mediated events can occur 
throughout the dendrite field, generating lossless sodium or calcium 
spike potentials which propagate to the cell body and interact on the 
way.  In addition, when the cell fires, the action potential spreads 
back into the dendrite field and interacts with synaptic events there.  
It ain't simple (and I would venture it's not modellable in any 
meaningful sense either!).
> I've read from Koch's "Biophysics of Computation" that it
> takes about 64 EPSP inputs *at* the soma close together to
> generate an action potential. (The threshold being about 16mV
> above resting potential and each EPSP typically around 0.3mV).

Not really a very meaningful statement, since EPSPs don't typically 
arrive on the cell body anyway - and their summation is a decidedly 
non-linear process.  The voltages would be microvolts, by the way, and 
threshold potential varies a great deal according to the type of neuron.
> Is it possible to actually discern individual contributions
> of EPSPs from such recordings? What about background noise
> that is not from EPSPs?

EPSPs are easily resolved, in fact events called "minis" are routinely 
resolved, which are the result of spontaneous release of a *single* 
transmitter vesicle at a synapse!  Generally patch clamps achieve a 
gigohm seal, meaning that the recordings are pretty robust and noise 
isn't a problem in a good rig with a good preamp.

Sorry for the negativity - I often feel that people who are confident 
that the brain can be computationally modelled at the cellular level, 
just don't understand the problem sufficiently.  I don't mean to say 
that the brain can't be computationally modelled using abstractions or 
analogies, but there is a very real gulf between the biological and the 
discrete which is not surmountable by any means I'm familiar with.



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