In a study on mice, a team of researchers from Tufts University School of Medicine and Yale University School of Medicine has discovered a molecular mechanism that is essential for maturation of brain function and may be used to restore cortical plasticity in mature brains.
Ribic et al discovered a new molecular mechanism that is essential for brain maturation and may be used to restore plasticity in aged brains. Image credit: Adema Ribic / Tufts University School of Medicine.
The human brain is very plastic during childhood, and all young mammals have a ‘critical period’ when different areas of their brains can remodel neural connections in response to external stimuli.
Disruption of this precise developmental sequence results in serious damage; conditions such as autism potentially involve disrupted critical periods.
“It’s been known for a while that maturation of inhibitory nerve cells in the brain controls the onset of critical period plasticity, but how this plasticity wanes as the brain matures is not understood,” said first author Dr. Adema Ribic, a researcher at Tufts University School of Medicine.
“We’ve had some evidence that a set of molecules called SynCAMs (synaptic cell adhesion molecules) may be involved in this process, so we decided to dig deeper into those specific molecules.”
Dr. Ribic and her colleagues focused on the visual cortex, the part of the brain responsible for processing visual scenes, in which plasticity has been examined in many species.
Ribic et al show that brain plasticity is actively restricted by the synapse-organizing molecule SynCAM 1. The protein acts in parvalbumin interneurons to recruit excitatory thalamocortical terminals. This controls the maturation of inhibition and actively limits cortical plasticity, revealing a synaptic locus for closure of cortical critical periods. Image credit: Ribic et al, doi: 10.1016/j.celrep.2018.12.069.
Using advanced viral tools and electrophysiological techniques, the researchers were able to measure activity of neurons in awake mice freely responding to visual stimuli.
They found that removal of the SynCAM 1 molecule from the brain increased plasticity in the visual cortex of both young and adult mice.
Further research found that SynCAM 1 controls a very specific type of neuronal connection termed synapses: the long-distance synapses between the visual thalamus, located beneath the cerebral cortex, and inhibitory neurons in the cortex.
SynCAM 1 was found to be necessary for the formation of synapses between thalamus and inhibitory neurons, which in turn helps inhibitory neurons to mature and actively restrict critical period plasticity.
Plasticity is needed during early development, as the function of different brain areas matures. Mature function is then ‘cemented’ into place by molecules like SynCAM 1.
“Our study identified a fundamental mechanism that controls brain plasticity, and perhaps most exciting, we can show that a process in the adult brain actively suppresses plasticity,” said Tufts University School of Medicine’s Dr. Thomas Biederer, senior author of the study.
“Therefore, the limited ability of the mature brain to change is not simply a consequence of age but is directly enforced by the SynCAM 1 mechanism.”
“This allows us to target the mechanism to re-open plasticity in the mature brain, which could be relevant for treating disorders like autism.”
The study was published in the journal Cell Reports.
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Adema Ribic et al. Synapse-Selective Control of Cortical Maturation and Plasticity by Parvalbumin-Autonomous Action of SynCAM 1. Cell Reports, published online January 8, 2019; doi: 10.1016/j.celrep.2018.12.069
