Fascinating topic, especially given how E/I imbalance is linked to several neuropsychiatric disorders such as epilepsy, autism or schizophrenia. [1]
Coincidentally, I published a paper in the Journal of Neuroscience during my PhD demonstrating with a simple mathematical model how E/I balance enabled neurons to be highly sensitive to precise spike timing. [2]
A show-HN mid-dive with Brian simulator would be cool
magicnubs•4mo ago
It all comes down to glutamate and gaba again. It's been really interesting to see how fundamental these two molecules are as I have learned more about medical biology/neurology. They are implicated in so many medical and psychiatric conditions, yet you tend to hear much more about the monoamine transmitters (serotonin, dopamine, norepinephrine, etc). But they are also hard to target for therapeutic purposes because gabaergics (barbituates, alcohol, z-drugs, etc) are often dangerously addictive; gaba just feels good... until the bill comes due. Maybe someday we will find a way to upregulate gaba activity in the body/brain without the inevitable crash. Hopefully we will, at least for the sake of people that suffer from over/under-excitatatory diseases.
storus•4mo ago
Have you heard of GlyNAC? It targets glutamate excitotoxicity and as glycine + NAC + glutamate form glutathione, it also delivers both molecules needed to assemble it alongside glutamate.
Llamamoe•4mo ago
It's because it's the other neurotransmitters that have neuromodulatory functions, often with specific subreceptors that perform specific roles.
In contrast GABA and glutamate mainly just handle the general information processing across the entire brain, there isn't a whole lot to do other than inhibit GABA which happens to reduce anxiety (as well as your entire brain's cognitive health)
rossant•4mo ago
Coincidentally, I published a paper in the Journal of Neuroscience during my PhD demonstrating with a simple mathematical model how E/I balance enabled neurons to be highly sensitive to precise spike timing. [2]
[1] https://pmc.ncbi.nlm.nih.gov/articles/PMC6742424/
[2] https://www.jneurosci.org/content/31/47/17193.short
gsf_emergency_2•4mo ago
(Or hodgkin-huxley with fewer)
A show-HN mid-dive with Brian simulator would be cool