[randomstudent]

> Hopefully some day we will find ways to drive repair of these circuits.

Any idea on how we may do it? AFAIK, currently we have no good mechanisms to "repair" individual brain circuits: even in strokes, we mainly exercise the affected area so that neural plasticity repurposes other neurons (usually in the cerbral cortex) to take over lost functions.

Does the hypothalamus have this degree of plasticity?

[subcosmos]

I saw a study once that raised mice on both standard and high fat chow. Predictably the high fat fed mice developed central obesity. (High fat diets are still a reliable way to make a mouse fat).

They then put the fat mice back on the normal chow, and they lost weight, but importantly they didn't ever reach the healthy weight of the mice fed on normal chow from the start.

The explanation they offered was that the GABAergic Agrp/NPY neurons (that promote hunger and lower metabolism) had formed stronger connections, and many of the Glutaminergic POMC/Cart neurons (that promote satiety and increase metabolism) had died off.

Whenever I go digging for this study I can't find it. Allison Xu's lab however has written a few studies now talking about this neural subtype ratio in various models, as well as the inflammatory mediators linked to their changes over time. http://www.pnas.org/content/110/8/E697.long

Im not sure about the plasticity questions, or neural regeneration, but that would be ideal if possible. I have however seen more crude suggestions for treatment that involve killing off neurons in the hypothalamic nuclei that promote hunger and feeding using techniques such as gamma knife radiotherapy. https://www.ncbi.nlm.nih.gov/pubmed/15695926

But it would be a LONG time before that becomes a viable surgery in humans!

[randomstudent]

Thanks. I'll read these papers he I have the time. I agree that gamma knife surgery on the hypothalamus is probably not yet ready for prime time (and it might never be if we can find something better)