Molecular mechanisms of synaptogenesis

Abstract

Synapses are the basic units for information processing and storage in the nervous system. It is only when the synaptic connection is established, that it becomes meaningful to discuss the structure and function of a circuit. In humans, our unparalleled cognitive abilities are correlated with an increase in the number of synapses. Additionally, genes involved in synaptogenesis are also frequently associated with neurological or psychiatric disorders, suggesting a relationship between synaptogenesis and brain physiology and pathology. Thus, understanding the molecular mechanisms of synaptogenesis is the key to the mystery of circuit assembly and neural computation. Furthermore, it would provide therapeutic insights for the treatment of neurological and psychiatric disorders. Multiple molecular events must be precisely coordinated to generate a synapse. To understand the molecular mechanisms underlying synaptogenesis, we need to know the molecular components of synapses, how these molecular components are held together, and how the molecular networks are refined in response to neural activity to generate new synapses. Thanks to the intensive investigations in this field, our understanding of the process of synaptogenesis has progressed significantly. Here, we will review the molecular mechanisms of synaptogenesis by going over the studies on the identification of molecular components in synapses and their functions in synaptogenesis, how cell adhesion molecules connect these synaptic molecules together, and how neural activity mobilizes these molecules to generate new synapses. Finally, we will summarize the human-specific regulatory mechanisms in synaptogenesis and results from human genetics studies on synaptogenesis and brain disorders.

Prefrontal cortex structural and developmental associations with callous-unemotional traits and aggression

“…While much of the existing literature and our discussion has focused on synaptic pruning, it is also possible that the negative associations that we observed between grey matter structure and CU traits/aggression in the younger children are reflective of deficits in synaptogenesis. Considering that the onset and cessation of synaptic pruning and synaptogenesis are thought to be spurred on by dissociable molecular mechanisms 54 , 55 , clarifying which developmental processes are aberrant in youths with high CU traits/aggression may allow future studies to generate specific hypotheses regarding the molecular features associated with these behavioural problems. Work of this nature may inform future targeted pharmacologic interventions that can be applied earlier in development.…”

The Implications of Microglial Regulation in Neuroplasticity-Dependent Stroke Recovery

“…Endogenous neurogenesis is closely related to synaptic formation or synaptogenesis, which involves the formation of neurotransmitter-secreted sites in the presynaptic neuron, a receptive field at the postsynaptic partners, and the exact alignment of pre- and post-synapses [ 66 , 67 ]. New synapses are formed throughout the life of an organism and they are especially prominent in the early development of the nervous system [ 68 ].…”

Neonatal sevoflurane exposure induces long-term changes in dendritic morphology in juvenile rats and mice

“…14 Genetic, environmental, or pharmacological factors can dysregulate synapse formation within this critical window. 15,16 During the early neonatal period, GA is a potent pharmacological disruptor of synaptogenesis. 17 As millions of immature neurons are being apoptotically deleted from the developing brain during the aftermath of anesthesia exposure, billions more surviving neurons are exposed to a toxic milieu as they actively engage in a physiological process that are fundamental to normal cognitive and socio-affective functions.…”