Brain’s immune cells put the brakes on neurons

[Andy]

Thought this was interesting.

Neural circuits in the brain rely on neuronal excitation (a positive change in the electrical potential across the cell membrane), combined with delayed inhibition (Fig. 1). Inhibition is crucial for keeping neuronal activity in the optimal range for encoding information, minimizing the brain’s energy use and computing useful neuronal outputs. It has conventionally been thought that inhibition is mediated by a neuronal subtype called interneurons that release neurotransmitter molecules (such as the amino acid GABA) to make the membrane potential of the downstream neuron more negative — although neurotransmitter release from non-neuronal cells called astrocytes can also contribute1. Writing in Nature, Badimon et al.2 extend this repertoire of inhibitory influences to include microglia, the resident immune cells of the brain. The authors’ work raises fascinating questions about the role of microglia in information processing.

https://www.nature.com/articles/d41586-020-02713-7

 

[Mithriel]

Epilepsy is when an electric discharge spreads through the brain. FND epilepsy could be caused by a problem with the inhibition system not cutting in properly so there is a wave of chemical activity.

That sort of delayed feedback could be the cause of a lot of problems in ME too. It is something that we could do with knowing more about.

 

[Andy]

I thought that it suggests a possible explanation for brain fog. The dampening activity of microglia is said, in the article, to be activated by ATP, so if there was to be increased extracellular ATP in patients (which may or may not be the case), then this dampening activity might be triggered more than it should be. Obviously a lot of ifs, buts and maybes, so certainly not anything proven, but an interesting thought nonetheless.

 

[Creekside]

It sounds reasonable to me. I'm convinced that my glial cells are closely involved in my ME, so this fits. It might not require increased ATP; it could be other mechanisms that affect how the glial cells function, which in turn affects the ATP->damping function.

Since many of us suffer from sleep problems, this part of that paper might apply:

"ADO derived from ATP released by astrocytes is proposed to regulate sleep onset10. Badimon et al. found that the extracellular level of ADO in a brain region called the striatum was reduced by 85% in anaesthetized mice lacking microglia, compared with control mice that had microglia. This suggests that the build-up of extracellular ADO that generates sleep pressure might largely be derived from the activity of microglial CD39. Thus, microglia-facilitated negative-feedback control of neuronal activity could be a side effect of the evolution of a system to induce sleep (or vice versa)."