Researchers here identify a mechanism that suppresses neural plasticity in the visual cortex of adult mice, a part of the developmental process that permits greater plasticity in childhood, but then restricts it in adults. This plasticity is the generation and integration of new neurons into neural circuits. Increased plasticity in adults may be beneficial, allowing for better maintenance and regeneration in the aging brain. That benefit must be balanced against whatever functional reason has led evolution to establish diminished plasticity with advancing age. If resistance to cancer is the answer, similar to the explanation for reduced stem cell function throughout the body in later life, then this can be addressed along the way. If there are other functional reasons for lower levels of plasticity in adults, and thus increased plasticity might damage the adult brain in some way, such as by causing disarray in established neural networks, then this will be more challenging to resolve.
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. We’ve had some evidence that a set of molecules called SynCAMs may be involved in this process, so we decided to dig deeper into those specific molecules.”
The study focused on the visual cortex, the part of the brain responsible for processing visual scenes, in which plasticity has been examined in many species. 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.
The researchers liken inhibitory neurons to a dial controlling when brain plasticity can occur. 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. “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. Combined with the latest approaches in genetic manipulation, this may prove to be a new path to tackle both childhood disorders and brain injury in adults.”