- Patch clamp experiments usually take place in slices with artificial cerebrospinal fluid (ACSF). The ephys properties can vary widely based on the experimental prep (angle that slice was taken, the temperature, the specific recipe used for the ACSF, the quality of the patcher, etc. etc.
even if patching worked really well and was robust and reliable, the ephys properties at the soma (where vast majority of patching willt ake place) hardly describe the ephys of the entire dendritic tree, which is very complicated and space dependent, and incredibly nonlinear and variable.
Based on this and you other comment you seem to be pro GEVI instead of patch clamp, am I correct? Assuming GEVIs were used (or some other, better technology) to find all electrophysiology, why would that be a waste of time? Even if we can get by with a few thousand template neurons and individual tuning is not necessary (which seems to be the view of Steven Byrne and maybe you) how should we go about getting those template neurons without a lot of research into correlating morphology, genetic expression, and electrophysiology? If we don’t need them, why would we not? My primary goal is not to defend my plan, I just care about making progress on WBE generally and I would like to hear specific plans if others have them. Studying single cell function just seemed to be the most natural to me. Without that, studying how multiple neurons signal each other or change over time or encode information in spike trains seems like putting the cart before the horse as it were. Again, very glad to be wrong, it just still seems to me that some version of this research has to be done eventually, we haven’t done it yet AFAIK, so I should start on what little part I can.
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Some reasons that come to mind very quickly:
- Patch clamp experiments usually take place in slices with artificial cerebrospinal fluid (ACSF). The ephys properties can vary widely based on the experimental prep (angle that slice was taken, the temperature, the specific recipe used for the ACSF, the quality of the patcher, etc. etc.
even if patching worked really well and was robust and reliable, the ephys properties at the soma (where vast majority of patching willt ake place) hardly describe the ephys of the entire dendritic tree, which is very complicated and space dependent, and incredibly nonlinear and variable.
Based on this and you other comment you seem to be pro GEVI instead of patch clamp, am I correct? Assuming GEVIs were used (or some other, better technology) to find all electrophysiology, why would that be a waste of time? Even if we can get by with a few thousand template neurons and individual tuning is not necessary (which seems to be the view of Steven Byrne and maybe you) how should we go about getting those template neurons without a lot of research into correlating morphology, genetic expression, and electrophysiology? If we don’t need them, why would we not? My primary goal is not to defend my plan, I just care about making progress on WBE generally and I would like to hear specific plans if others have them. Studying single cell function just seemed to be the most natural to me. Without that, studying how multiple neurons signal each other or change over time or encode information in spike trains seems like putting the cart before the horse as it were. Again, very glad to be wrong, it just still seems to me that some version of this research has to be done eventually, we haven’t done it yet AFAIK, so I should start on what little part I can.