Microglia as Regulators of Neural Transmission

This study, freely available here(4.61MB), has some striking implications. These are listed below. The Science Daily news release can read here. Microglia are typically perceived as the immune cells of the CNS but this study builds on former studies all pointing to the possibility that our current understanding about neural transmission and memory is too constrained. This present study indicates:

• Microglia regulate the fate the synapses
• Microglia are constantly on the move and at a rapid pace.
• Microglia may be regulating memory consolidation.
• Our conceptual separation of immune processes and neural transmission is a fundamental error.

I included that last point because several years ago I had some email discussions with a bod in Britain, clever psychologist, where the question, "just what is the neural code" was being addressed. He stated that at present we don't have the conceptual tools to address the question. Still true. I threw something out though that caught him off guard. At the time I was swamping my brain with neuroimmunological data, so as the old saying goes, to a man with a hammer, I threw this at him: "As a starting point we might want to consider the similiarities between nervous and immune functions." I made this statement because:

• Although I cannot find this in the text now, at the time I remembered that in Bright Air, Brilliant Fire, Gerald Edelman asserted that both the immune and nervous progenitor cells originated from the same embryonic tissue.
• We have two memory structures: CNS and immune.
• There is a striking set of cross overs of molecular messengers between the CNS and Immune functions. 
• Pain can be mediated by immunological processes, hence there is more to perception than nerves. 
• There is a mountain of data  indicating that modulation of various immunological processes has important implications for behavior and neural transmission. 

At that time I had no idea as to how further investigate that idea. I still don't but this paper shows that people are finding ways to investigate this issue. This present study is quite striking and offers some novel possibilities for visualising and understanding the role of microglia in the CNS.

The current textbook view is that microglia are basically hanging about and in a resting state, perhaps providing some trophic and nutrient factors to neurons. They only get motivated when something bad is happening. This study, and many other preceding it but this one has the great advantage of powerful visualisation of microglial movement, indicate that microglia are generally on the go, and not just immune cells but active participants in synaptic consolidation and possibly destruction. The key findings are:

• Even in the so called resting state microglia are constantly extending processes into the extra-cellular space, as if "exploring by touch". 
• Using light as the stimulus they found that microglia quickly became active, phagocytosing some synpases(consuming them). 
• Microglia would extend long processes that wrapped around the spines of neurons.
• Microglia seemed to be constantly "in touch" with synapses by these processes.

There is lots of fascinating stuff in this paper. I haven't had time to read this paper carefully but I am surprised that during the stimulus increased phagocytosis of synapses occurred, I would have anticipated the opposite. However, I just remembered at a conference this bod said that synaptic numbers could change extremely quickly with no apparent change in behavior(rats).

Now then, remember that idea that there is a surplus of synapses? If a signal travels down an axon to a large number synaptic targets is it conceivable that a higher rate of synaptic consolidation can occur by reducing the total number of synapses requiring consolidation? The large number of synapses may simply be a function of growth processes that increases the probability of contact with other cells.

Finally,

This paper challenges some of our fundamental assumptions about the function of nervous transmission and memory consolidation. To further complicate matters, it is also the case that there is no clear distinction between the endocrine processes and the above. Perception is a function of the body, not just the brain.