During childhood, the human brain is highly sensitive and will form connections to best adapt to its environment. This ability, called plasticity, diminishes as we age. Rebooting this ability may be the key to everything from treating neurodegenerative disease to helping the brain heal from trauma.
In the lab of Dr. Etienne de Villers-Sidani at The Neuro, researchers study the fundamentals of brain plasticity. The goal of this work is to develop therapies and strategies to help neurological patients.
A paper published recently from his lab was the first to show that brain plasticity can be regained by manipulating a specific type of neuron in the auditory cortex of rats.
Called a Parvalbumin-positive (PV+) cell, it has been the subject of many neuroplasticity studies, as it is involved with the opening and closing of developmental critical periods. These are times when an organism is most susceptible to changes in brain connections due to its environment. Previous studies in the auditory cortex however have not been specific enough to the cell to define its role in plasticity.
Dr. Mike Cisneros-Franco, a PhD candidate in Dr. de Villers-Sidani’s lab, set out to better define the role of PV+ cells in the auditory cortex, the brain region that processes sound.
Using chemogenetics, the delivery of compounds that alter the way genes are expressed, he shut down PV+ cells in rats and recorded the reaction of their auditory cortex to sounds of various frequencies, then compared them to a control group of rats with normally functioning PV+ cells.
Certain neurons of the auditory cortex become attuned to certain frequencies while the brain is plastic, then keep this specialization when plasticity goes away. When PV+ cells were deactivated, these neurons became attuned to a wider range of frequencies than in the control group, showing that plasticity had been boosted. This proves that PV+ cells inhibit plasticity in the auditory cortex, acting as a sort of cement that keeps what was learned during critical periods in place.
The results demonstrate for the first time that it is possible to change the way the adult rat brain responds to sounds by controlling the activity of PV+ cells. These cells are affected in a range of conditions, including traumatic brain injury, chronic noise exposure, autism and schizophrenia. Promoting neuroplasticity by inhibiting PV+ cells in humans may hold promise for helping patients manage or recover from neurological disease and disorders.
“It was very exciting to see that even after a few minutes of sound delivery, the inhibition of these cells was already leading to increased brain plasticity,” says Dr. Cisneros-Franco. “While this plasticity occurred during passive experience, I’m more interested in plasticity during learning. We are currently studying how manipulating PV+ cell activity affects the rate and quality of learning.”
The main objective of this research project was to investigate what are the best ways to make the adult brain more plastic?
That is, we wanted to change the way the brain responds to sounds and the way their brain functioning connected. So what we did was we took a group of rats and we exposed them to tones of different sounds.
Normally it doesn't change the rat brain but when we did some genetic manipulation and we shut down some specific types of neurons then we were able to change the brain by just passively listening to these sounds.
The cells we studied are really interesting because these are affected, for example, in ageing, in neuropsychiatric disorders such as autism or schizophrenia, but also after brain trauma or noise exposure.
What we want to do is try and learn how these cells work so we can harness plasticity in the developing and in the adult brain.