[Eeglablist] Open online discussion: How Do Cable Theory and AMPA/GABA Balance Compare in Their Contributions to 1/f?

[Евгений Машеров]

> Hi Makoto and everyone,
> 
> I won't be able to attend unfortunately. One thing I am curious about is why we mainly focus on AMPA receptors as the excitatory model. I am no expert here, but from what I recall from undergrad classes, NMDA receptors are the dominant glutamate receptors in the human brain, so it feels like they should probably be included if we want to better understand the aperiodic background at the neuronal level?
> 
> According to an AI-assisted exploration (to be fact-checked), AMPA receptors are simpler to model because they are fast and Ca2+-impermeable, with stereotypical decay kinetics that map cleanly onto cable theory. NMDA, on the other hand, has a voltage-dependent Mg2+ block that introduces nonlinearities, which is why it tends to appear in more sophisticated compartmental models combining Hodgkin-Huxley conductances with multi-compartment cable structure (https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/8684467/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8URMHPkFbA$ ; https://urldefense.com/v3/__https://pmc.ncbi.nlm.nih.gov/articles/PMC10600871/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8UQ7a9S8hw$ ).
> I believe Eugen and Makoto (and others) have already discussed on Github the possibility that one of the mechanisms underlying 1/f-ness is electrodiffusive, related to ionic diffusion in the extracellular medium and how voltage signals filter through brain tissue (https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/17025932/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8UQL2GLiYA$ ; https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/19348744/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8URLWVnFGQ$ ).
> Including NMDA feels relevant here because its slow, voltage-dependent conductance would extend the source signal spectrum, while electrodiffusion shapes it on the propagation side.
> 
> Specifically:
> - Multi-timescale kinetics. NMDA decay constants (~50-500 ms for NR2B) combined with AMPA (~5 ms) and GABA-B (~200 ms) naturally produce power-law-like spectra over a wider frequency range via superposition of Lorentzian processes, making the 1/f approximation more robust (https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/15483395/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8UQnALGmEQ$ ).
> - Distal dendritic enrichment. NMDA receptors are concentrated on apical dendrites where cable filtering is strongest, potentially producing location-specific spectral signatures.
> - Tonic NMDA activity. In high-conductance background states realistic in vivo, membrane fluctuations may regularly push voltage past the Mg2+ unblock threshold, contributing a slowly fluctuating conductance noise critical for the low-frequency end of the 1/f spectrum.
> - Interaction with HCN (Ih) channels. Both are voltage-dependent and co-localized in distal apical dendrites (https://urldefense.com/v3/__https://pubmed.ncbi.nlm.nih.gov/25609619/__;!!Mih3wA!FIzLKzvJ2yvgcESdkJKVn6WMFR279-nFGjfNcMr1mO_rEcMhkKcRqWkebEG4KRMHmf4jQgYzj18GHSUE8USX3x02ZA$ ), so their interaction would probably be unavoidable in any realistic model.
> 
> Anyways, that's AI-heavy so to judge with caution, but it feels like there may be some useful food for thought in here.
> 
> Cedric

It seems to me that the choice of these two receptors is related to their role in the formation of EPSPs and IPSPs, respectively. EPSPs and IPSPs are often considered the sole (though I personally disagree) source of the EEG, as they generate a dipole potential. NDMA, if I understand correctly, influences the potential, but the resulting field is somewhat monopolic. Therefore, I fully agree with the thesis that taking these receptors into account is also necessary, although fully accepting this principle would lead us to a "richess embarrassment," since over a hundred neurotransmitters are known, and which others need to be considered is unknown.
In any case, it's worth considering the dynamics of not only sodium and potassium ions, but also calcium and magnesium. Their purely electrical contribution may not be as great compared to Na and K, but they are involved in regulating the sodium-potassium pump (Mg participates in the cycle, while Ca can act as a competitor, blocking its function).

Eugen Masherov