Study shows how brain removes unnecessary synapses to create new connections

Synapses that don’t show enough activity are pruned, a new study in mice shows. This means that neural connections that are not used can be removed from the brain. This process is called competitive work between neurons, where often-activated connections are strengthened and little-used ones are pruned.

The study was conducted on mice and used mitral cells, a type of cell located in the olfactory bulb, the brain center responsible for our sense of smell. Adult mitral cells were found to have a single connection to an intermediate signaling station called the glomerulus. However, in early development, mitral cells branch off from many glomeruli. Over time, these branches are cut off, leaving a single strong connection. For the mice used in this study, this process for most mitral cells is completed by day 6 after birth.

Although some mechanisms linking neuronal activity and synaptic contraction have been proposed previously, this article puts forward a different idea. It is the transmission of signals from glutamate that was necessary for pruning. When glutamate binds to its NMDAR receptor in the dendrite, it suppresses a molecule of the pruning mechanism called RhoA. This “save me” signal is important for protection against pruning. However, this signaling pathway does not affect other dendrites as well, causing RhoA activation for them rather than suppression.

This “punishment” signal for synapse destruction only affects unprotected synapses, and it explains how only a strong connection becomes a winner, while all others mediating weak and noisy inputs become losers.

However, scientists caution that NMDARs are not considered critical for synaptic function in some systems, including neuromuscular connections. It remains to be seen whether the same principle is involved in these systems.

This research helps to better understand the mechanisms underlying competitive work between neurons and may be useful for the development of new treatments for neural diseases.

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