A Focus on Synaptic Densities Might be the Future of Neuroscience

Behavior, neural function and synaptic connectivity have long been suspected to be interconnected, but the advent of studying synaptic density using positron emission tomography might lead to definitive answers regarding mental illnesses and neurodevelopmental conditions. 

Unmedicated individuals, afflicted by major depressive disorder and post-traumatic stress disorder were shown to have significant synaptic loss and deficits in functional connectivity (Holmes et. al., 2019). The severity of depressive symptoms was also shown to be inversely correlated with synaptic vesicle glycoprotein 2A - an indirect means of measuring synaptic density. This lack of synaptic connectivity evident in both disorders - likely caused by various forms of stress - can also be linked to a loss of volume in the prefrontal conrtex, anterior cingulate cortex and the hippocampus, all of which are major areas of the brain associated with cognition and affect. The effects of these losses of synaptic connection are wider ranging than this. The research suggested low numbers of synapses are responsible for feeling more severe symptoms of these disorders, potentially highlighting neurodegenerative diseases targeting networks in the brain. 

The effects of substances in reversing these synaptic deficits is another facet of these disorders that has been studied. When treated with ketamine, increased antidepressant properties could be seen in models alongside an increase in the number and function of synaptic connections. Similar effects can also be seen in prefrontal cortex connectivity. Researchers theorize that enhancing synaptic connection and plasticity might be a means of restoring executive control, while also explaining the therapeutic effects of certain antidepressants. 

The use of radioligand binding to synaptic vesicle glycoprotein 2A provides an opportunity to study and understand these diseases better than we have before. It exists in synapses across the brain, in consistent concentrations at each synapse, making it the perfect molecule to track. Its functions are still a relative mystery, so focusing on understanding its purpose, alongside its use for in vivo modeling of synapses in the brain makes it the ideal focus for neuroscience research. 

Link to the paper: https://www.nature.com/articles/s41467-019-09562-7#citeas