Researchers identified a new group of proteins that help the brain to control its activity, including several proteins found to be altered in epilepsy patients. This finding sheds light on what is known about the specific neurons that regulate neuronal communication, called inhibitory neurons, and may be an important contribution to the study of diseases in which brain activity is poorly regulated, including epilepsy.
The study, “Identification Of An Elaborate Complex Mediating Postsynaptic Inhibition,” was published in the journal Science and conducted by researchers at Duke University.
In a healthy brain, communication between neurons depends on several proteins that, working together, propagate electrical signals. The space between two neighboring neurons is called the synapse, and this is where electrical signals are passed along from one neuron, or nerve cell, to the other. The neurons that work to activate the others are the excitatory neurons.
However, to assure that neuronal communication is not exaggerated or otherwise dysregulated, other neurons have to control their activity. These inhibitory neurons act, as their name implies, as a brake on excitatory neurons, whose uncontrolled activity can induce seizures and other adverse events.
Many proteins have been identified as key players in excitatory neurons, but the proteins of inhibitory neurons are largely unknown. Scientists also believed these neurons were simpler than their excitatory counterparts, involving fewer proteins — but this study implies otherwise.
“It’s like these proteins were locked away in a safe for over 50 years, and we believe that our study has cracked open the safe,” Scott Soderling, PhD, the study’s lead author, said in a news release. “And there’s a lot of gems.”
The researchers used mice to test a recent technique, called BioID, that uses a bacterial protein that binds to any proteins in its vicinity. The captured proteins were then recovered, and identified using standard methods for protein identification. As many as 140 proteins were identified in inhibitory neurons, 27 of which had already been found to be altered in patients with epilepsy, autism, and intellectual disability. It may be that mutations in the genes encoding these control proteins contribute to the onset and development of these diseases.
“Finding them at the inhibitory synapse really gives us important insights,” Soderling said. “The hypothesis now is that these mutations are impairing the ability of neurons to inhibit activity. That’s something that we’re actively studying.”
Among the proteins identified, two had no known function, so the team dubbed them Inhibitory Synapse 1 (InSyn1) and Inhibitory Synapse 2 (InSyn2). To understand what could be the function of InSyn1, researchers inhibited the production of this protein in individual neurons, which caused the overactivation of neighboring neurons. This result showed that InSyn1, indeed, has a role in controlling the activity of the other neurons.
The team also plans to study the contribution of the inhibitory neurons in the formation of memory, a process dependent on a balance between excitation and inhibition in the brain, and about which little is known.
