Efficient communication between neurons is crucial to the normal functioning of the brain and the cellular basis of thinking and movement control. The synapse is the specialized anatomical site where signals running along axons are transmitted to the postsynaptic cells. This is the main functional unit that enables chemical and electrical communication between brain cells to understand micro and macro-connectivity in the central nervous system. Three main functional spaces can be delineated in the synapse: the presynaptic terminal, the synaptic cleft and the postsynaptic terminal.
The pre-synaptic terminal receives the electric impulse of the action potential that travels across the axon coming from the neuronal body. When the action potential reaches the axon terminal it stimulates the release of neurotransmitter molecules stored at sacs called vesicles. They have particular characteristics regarding lipid and protein membrane composition and can be considered cell organelles. They need specific transporters to be moved towards the presynaptic membrane. Once at the presynaptic membrane they release neurotransmitter molecules into the synaptic cleft. Then vesicles experience exocytosis and are reabsorbed and incorporated into the vesicle cycle. Calcium (Ca 2+) has a critical role in exocytosis.
The synaptic cleft is the physical space where neurotransmitters (such as dopamine, serotonin, glutamate, GABA….), neuropeptides and other neuromodulators are released. While fast synaptic transmission uses neurotransmitters, peptides and proteins released from nerves may have slower and longer-lasting effects on postsynaptic cells and can modulate the response to fast neurotransmitters. Specific transporters are used to reuptake neurotransmitters into the pre-synaptic terminal. They modulate the time exposition of this particular neurotransmitter in the synaptic space and therefore in the pos-synaptic neuron. Astrocytes have important roles here not only due to their capacity to secrete glyotransmitters but also because they can re-uptake substances such as glutamate and modulate the post-synaptic signal.
The post-synaptic terminal is the place where the transmitter molecules produce receptor-mediated signaling, and therefore establish neural communication. Cell-surface receptors utilize four distinct molecular mechanisms for transmembrane signaling: ligand-gated ion channels, receptors with intrinsic guanylcyl cyclase activity, those with tyrosine kinase activity and G-protein-coupled receptors. Cross-talk can occur between intracellular signaling pathways.
Biological dysfunction in any of the steps of synaptic transmission often is the source of neurological symptoms and diseases. The particular characteristics of synapses in children and adolescents contribute to specific neurological symptoms at different developmental stages.
