Manipulating a specific type of neuron in the auditory cortex of rats can restore their brain plasticity, McGill University researchers report.
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.
A type of neuron called a parvalbumin-positive (PV+) cell 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.
Auditory Cortex Plasticity
Previous PV+ studies in the auditory cortex however have not been specific enough to the cell to define its role in plasticity. In the new work, the researchers 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, they 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.
[caption id=“attachment_101868” align=“aligncenter” width=“700”] Effects of PV+ cell manipulation on A1 anatomical and functional properties.
Credit: J. Miguel Cisneros-Franco and Étienne de Villers-Sidani CC-BY.[/caption]
Certain interneurons of the auditory cortex become attuned to certain frequencies while the brain is plastic, then keep this specialization when plasticity goes away.
When the researchers deactivated parvalbumin-positive cells, these neurons became attuned to a wider range of frequencies than in the control group, showing a boost in plasticity. 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.
Rate Of Learning
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. A range of conditions, including traumatic brain injury, chronic noise exposure, autism, and schizophrenia, affect these cells.
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. 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,”
says coauthor Mike Cisneros-Franco of the Montreal Neurological Institute-Hospital at McGill University.
Parvalbumin is a calcium-buffer protein involved in the modulation of short-term synaptic plasticity.
 J. Miguel Cisneros-Franco, Étienne de Villers-Sidani. Reactivation of critical period plasticity in adult auditory cortex through chemogenetic silencing of parvalbumin-positive interneurons. Proceedings of the National Academy of Sciences Dec 2019, 201913227; DOI: 10.1073/pnas.1913227117
Top Image: J. Miguel Cisneros-Franco and Étienne de Villers-Sidani CC-BY.