Microglia are involved in synapse maintainence

Microglial P2Y12 is necessary for synaptic plasticity in mouse visual cortex.Sipe GO, Lowery RL, Tremblay MÈ, Kelly EA, Lamantia CE, Majewska AK. Nat Commun. 2016;7:10905. doi: 10.1038/ncomms10905.

Microglia are the resident immune cells of the brain. Increasingly, they are recognized as important mediators of normal neurophysiology, particularly during early development. Here we demonstrate that microglia are critical for ocular dominance plasticity. During the visual critical period, closure of one eye elicits changes in the structure and function of connections underlying binocular responses of neurons in the visual cortex. We find that microglia respond to monocular deprivation during the critical period, altering their morphology, motility and phagocytic behaviour as well as interactions with synapses. To explore the underlying mechanism, we focused on the P2Y12 purinergic receptor, which is selectively expressed in non-activated microglia and mediates process motility during early injury responses. We find that disrupting this receptor alters the microglial response to monocular deprivation and abrogates ocular dominance plasticity. These results suggest that microglia actively contribute to experience-dependent plasticity in the adolescent brain.

Synaptic pruning refers to the process by which extra neurons and synaptic connections are eliminated in order to increase the efficiency of neuronal transmissions.

Synaptic prunning or axon prunning is the process of synapse elimination that occurs notably between early childhood and the onset of puberty in many mammals, including humans.Prunning starts near the time of birth and alot is completed by the time of sexual maturation in humans. This may be a reason why smoking pot is not the best idea during that time, as cannabinoids can alter synaptogenesis and the brain doesn’t completely develop until your early twenties. At birth, the human brain consists of approximately 86 (± 8) billion neurons. The infant brain will increase in size by a factor of up to 5 by adulthood. Two factors contribute to this growth: the growth of synaptic connections between neurons, and the myelination of nerve fibres; the total number of neurons, however, remains the same. Prunning is influenced by environmental factors and is widely thought to represent learningand so you need to prune throughout life. What this study indicates is that microglia are involved in that pruning ad they probably ingest the underused synapses.

In this study the the experimenters blocked vision in one eye during times when the brain is learning, no I don’t have time to discuss the visual system and the P2Y12 receptor as you can read the open source paper if you want. However it indicates that microglia and involved in this process. We also believe  they are involved in the repair process and are probably also involved in the damage process too. We want to target hot microglia but this post serves to show that microglia can do useful things as well, so blocking this aspect of the immune system may have its problems too.  

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  • Thanks for this post. I have heard of recent work from Beth Stevens lab, they looked at synaptic pruning in development, where both microglia and complement are involved. SOunds that neuron-glia interactions are at the forefront

  • Great article thanks. I read an article on PubMed that shows that viral RNA can directly cause microglia and macrophages to act in different ways. Is it possible that viral RNA directly from EBV directly induces "hot" or destructive microglia and macrophages accounting for neuron and axon destruction (progressive MS) and that RRMS is just a secondary autoimmune reaction to this process by T and B cells? Is there a developed monoclonal antibody or drug available that will slow or dampen the inappropriate response of these microglia and macrophages?

  • There is a significant amount of research coming out of the University of Rochester. I am local to them, their focus on neurological aspects of understanding the processes in the CNS is and then some is remarkable.

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