Synaptogenesis

Synaptogenesis is the process by which neurons form chemical and electrical synapses with target cells, enabling the establishment of neural networks. It begins during embryonic and early postnatal development and continues, in a more limited form, into adulthood, especially in brain regions involved in learning and memory.

The process proceeds through stages. First, axons extend growth cones that explore the environment and make contact with appropriate target neurons. Specific adhesion molecules and secreted guidance cues promote initial contact and target recognition. Next, pre- and postsynaptic specializations differentiate: synaptic vesicle release machinery assembles presynaptically and postsynaptic densities cluster receptors and scaffolding proteins. This leads to functional synapses, with neurotransmitter release and receptor responsiveness.

Maturation involves enlargement of the synapse, increased number of vesicles, and strengthening of transmission. Excitatory (often glutamatergic) synapses typically form on dendritic spines and recruit AMPA and NMDA receptors, whereas inhibitory (often GABAergic) synapses form on cell bodies and proximal dendrites with receptors such as GABA_A and associated scaffolds. Activity-dependent processes, calcium signaling, and activity-regulated genes refine synaptic contacts and are influenced by neurotrophins like BDNF.

Glial cells, particularly astrocytes and microglia, promote synapse formation and elimination, contributing to pruning and maturation. Aberrations in synaptogenesis are linked to neurodevelopmental and psychiatric disorders.

Understanding synaptogenesis illuminates how neural circuits are built and modified, supporting learning, memory, and adaptation throughout life.