How does synaptic pruning happen?

[Priyadarshini]

Hi,
I was wondering how synaptic pruning occurs? I understand the need for pruning, but how do connections in the brain just disappear? Are there molecules or enzymes that break neurone cells down, causing the loss of a connection, or is there some other mechanism?
Thanks!

 

[jedishrfu]

From the wiki article:

https://en.wikipedia.org/wiki/Synaptic_pruning

They mention that while they know it happens the actual molecular mechanisms are still unclear:

Mechanisms
The three models explaining synaptic pruning are axon degeneration, axon retraction, and axon shedding. In all cases, thesynapses are formed by a transient axon terminal, and synapse elimination is caused by the axon pruning. Each model offers a different method in which the axon is removed to delete the synapse. In small-scale axon arbor pruning, neural activity is thought to be an important regulator,[citation needed] but the molecular mechanism remains unclear. Hormones and trophic factors are thought to be the main extrinsic factors regulating large-scale stereotyped axon pruning.[5]

 

[BillTre]

I don't think this is entirely worked out in all cases, but here is a story about a someone studying a mechanism where synapses to be eliminated are in someway decorated with some complement proteins (proteins best know for they involvement in blood clotting). The parts labeled with complement are then eliminated by microglia (which some call the immune cells of the brain).

 

[Fervent Freyja]

I found this interesting, though lengthy: Synaptic pruning in the female hippocampus is triggered at puberty by extrasynaptic GABAAreceptors on dendritic spine

Adolescent synaptic pruning is thought to enable optimal cognition because it is disrupted in certain neuropathologies, yet the initiator of this process is unknown. One factor not yet considered is the α4βδ GABAA receptor (GABAR), an extrasynaptic inhibitory receptor which first emerges on dendritic spines at puberty in female mice. Here we show that α4βδ GABARs trigger adolescent pruning. Spine density of CA1 hippocampal pyramidal cells decreased by half post-pubertally in female wild-type but not α4 KO mice. This effect was associated with decreased expression of kalirin-7 (Kal7), a spine protein which controls actin cytoskeleton remodeling. Kal7 decreased at puberty as a result of reduced NMDAR activation due to α4βδ-mediated inhibition. In the absence of this inhibition, Kal7 expression was unchanged at puberty. In the unpruned condition, spatial re-learning was impaired. These data suggest that pubertal pruning requires α4βδ GABARs. In their absence, pruning is prevented and cognition is not optimal.

 

[BillTre]

Then you may find the protein of the KISS1 gene interesting (wikipedia).
Its a ligand for a G-protein receptor that does a bunch of stuff, but at puberty it cranks up GnRH (Gonadotrophic Releasing Hormone) release in the hypothalamus.
This triggers gonadotrophin release (and may increase gene expression at certain points in development) from other cells (pituitary), which in turn stimulates the gonads (more development and hormone release).
It all ends up in sex, which then allows the pattern to be repeated in the next generation.

 

[atyy]

Two famous special cases in which there is synapse elimination so that only one neuron remains:

- neuromuscular junction:
http://www.ncbi.nlm.nih.gov/pubmed/24790203
http://www.ncbi.nlm.nih.gov/pubmed/26755586

- cerebellum:
http://www.ncbi.nlm.nih.gov/pubmed/23359672

Some recent work about pruning in the cortex
http://www.ncbi.nlm.nih.gov/pubmed/26255771

Review of cortical pruning phenomenology
http://www.ncbi.nlm.nih.gov/pubmed/25161611