Without synaptic "nibbling," mice develop behavioral problems

Mice without microglia grow up with an excess of inhibitory neurons

Black and white mice crowded together

Via Wikimedia

Synapses are the connection points between neurons where information is exchanged through chemical signals. As infants, we have an abundance of these connections, but when we transition into adulthood, the number of synapses in our brains decrease substantially. During this process, called synaptic pruning, unnecessary synapses are eliminated in order to strengthen the most important ones. By reducing synapses, the brain refines the circuits that allow us to learn, remember, and function properly throughout our lives.

One of the key players involved in pruning are microglia, the immune cells of the brain. Microglia “nibble” at pieces of synapses, which allows new connections to form as the brain is remodeling during development. Researchers have been investigating how microglia can target specific types of synapses and why microglia nibble some synapses in favor of others.

A group of scientists recently discovered a subset of microglia that make direct contact with inhibitory synapses. These synapses can be thought of as a brake pedal, and when they release the neurotransmitter GABA, they subdue activity of the cell receiving the signal. Interestingly, microglia make most of these contacts with GABA synapses early in life, during the prime time for synaptic pruning.

The researchers used mice to find out the role of microglia in the development of these connections. They treated newborn mice with a compound that diminishes microglia during the critical window when those microglia would typically be most active in pruning. When the microglia-deficient mice grew up, their brains contained more inhibitory synapses compared to mice that grew up with intact microglia. Genetically altered mice that lacked microglia with GABA receptors were also impacted behaviorally, displaying more hyperactive tendencies.

Microglia are crucial for remodeling synapses in the brain early in life. When microglia functioning is disrupted, it can affect synaptic pruning and lead to behavioral disorders including schizophrenia and ADHD. By characterizing different subtypes of microglia and how they interact with neurons, scientists are revealing how synapses become mature and how these processes can go awry.