CSHL Experts Gain New Insight into How Synapses Form

The billions of neurons our brains have communicate with each other through intricate networks of trillions upon trillions of connections called synapses, the formation and development of which play a pivotal role in what our cortices can do. Now, experts gain new insight into how synapses form.

The new study was conducted by investigators at the Cold Spring Harbor Laboratory (CSHL), in the US, who were led by professor Z. Josh Huang, PhD.

According to the team, the research largely revolved around the developing brain. This is a critical stage for the future individual, in which neurons begin to seek each other out, and form connections to underlie various cognitive abilities.

One of the most remarkable abilities that our brains have is that of neural circuitry self-assembling, which is a very complex process that underlies so-called synapse validation.

If this process fails, or somehow gets hijacked, then the resulting imbalances can give rise to a wide variety of neurodevelopmental disorders such as autism and schizophrenia.

Researchers figured out a long time ago that synapse formation is activity- or use-dependent, which means that it is triggered as a response to certain repeated activities or thought processes.

Before nerve cells hook up to each other, there are some preliminary stages to complete first. A bunch of “test messages” are passed between two unconnected neurons, to test compatibility. If this stage is cleared, than a process called cellular adhesion brings the two cells into physical contact.

Using an observations technique called two-photon microscopy, the CSHL team was able to observe synapse validation for the first time in living cortical circuits, as in in living organisms.

Details of the research were published online ahead of print in the December 13 issue of the esteemed journal Proceedings of the National Academy of Sciences (PNAS).

The work was focused on GABAergic inhibitory neurons, which communicate via neurotransmitters called GABA (gamma-aminobutyric acid).

“The question is: how can you form synapses with the right partners, and what mechanism is involved to achieve the necessary specificity?” the team leader says.

“But when you are in the cortex, the distance between different potential partners is so minute – it’s inconceivable that kind of mechanism could work,” he adds.

“It’s more plausible that the cortical neuron’s strategy is to initiate synapse formation with almost any nearby target and then to test it, by trying to communicate using synaptic transmission,” Huang reveals.

“Most of these tentative connections don’t prove to be correct and will be eliminated. Only those between functionally compatible neurons will be validated and strengthened,” he concludes.