Researchers at the University of Washington Faculty in St. Louis have overturned Dogma of decades of how connections between brain cells are reorganized during states of greater surveillance or attention. The team discovered that a brain chemist associated with the state of alert, attention and learning alters connectivity and brain function not acting directly in neurons, the cells known for their rapid transmission of information, but through the work of astrocytes, another type of slower cerebral cell of action that is often overlooked in the field of neuroscience.
The discovery, published in Science On May 15, the current understanding of the determinants of the communication and activity of the brain network changes. It also requires a greater focus on astrocytes as therapeutic objectives in the treatment of attention, memory and emotional disorders.
“Textbooks tell us that neuromodulators such as fine noreprenaline tunne neurons directly; in fact, textbooks tell us that everything in the brain is about neurons,” said Thomas Papauin, PHD, assistant professor of neuroscience at Washu Medicine and main author of the study. “It seems that a large amount of brain wiring and activity is probably orchestrated by astrocytes, in slower time scales. This is the type of discovery that deeply reforms our understanding of how the brain works.”
From the alhelí of the brain to the center of the stage
In order for the brain to be dedicated to the tasks that need attention, or to respond to unexpected stimuli such as a fire alarm, it should be able to requested again changing how brain cells communicate. This process is driven by the release of chemicals known as neuromodulators, including norepinephrine, in the brain. The way in which these neuromodulators reorganize communication in the brain is known little. The supply of the last 80 years has been that the neuromodulatory chemicals act on neurons.
Meanwhile, for at least 30 years it has been shown that astrocytes contact and interact with synapses, which are specialized structures where neurons communicate with each other. The researchers have suspected for a long time that astrocytes had the potential to reorganize communication between neurons and, therefore, the flow of information in the brain.
Due to their very fine and extensive shape, these cells are ideally positioned to monitor and detect neuromodulators such as norepinephrine. “We wanted to prove the idea that perhaps the neuromodulation of norepinephrine synapses is an astrocyte business,” Papouin said.
To do so, Papuín and his team stimulated the norepinenialic secretion of mouse brain cells or mouse brain slices exposed to norepinephrine and discovered that norepinephrine weakened the connections between neurons, as is known for decades. However, the researchers found that norepinephrine also triggered the activity among surrounding astrocytes. Once triggered by norepinephrine, astrocytes produced a second chemical that released in synapses, which caused the cushion of synapse activity. Even when the ability of neurons was eliminated to detect norepinephrine directly, noreprenaline could still reorganize neuronal connections. When the ability of astrocytes to feel or respond to norepinephrine was disconnected, on the other hand, norepinephrine could not reorganize neuronal connectivity.
Their findings indicate that neuromodulators such as noreprenaline reorganize neuronal connections in the brain by pointing through astrocytes instead of directly to neurons.
The results also suggest that addressing astrocytes could be an effective way to remodel brain activity to potentially treat brain disorders. Papouin’s team has begun to look at existing medications that are believed to act on neurons, to see if they require astrocytes. If so, perhaps astrocytes could be attacked directly for therapeutic purposes.
“There are so many medications that interfere with the signaling of norepinephrine in the brain, particularly in the treatment of ADHD or depression. I wonder how many of them require astrocytes to modify brain activity,” Papouin said.