Structural Biochemistry/Synaptogenesis

Overview
Synaptogenesis is the formation of synapses between neurons and the final step in the development of the central nervous system (CNS). This occurs through two steps. The first step is the contact of an axonal growth cone, an extension of a developing axon, to its partner cell. The second step are the axonal and dendritic protein components coming to the site of contact and ultimately forming a functional synapse.

Neuromuscular Junction
NMJ forms in a series of steps that involve the exchange of signals among its three cellular components nerve terminal, muscle fiber, and Schwann cell. The neuromuscular junction (NMJ) is the most well-characterized synapse in that it provides a simple and accessible structure that allows for easy manipulation and observation. The synapse itself is composed of three cells: the Motor neuron, the myofiber, and the Schwann cell. In a normally functioning synapse, when a signal causes the motoneuron to depolarize, the motoneuron releases the neurotransmitter acetylcholine (ACh). Acetylcholine travels across the synaptic cleft where it reaches acetylcholine receptors (AChR) on the plasma membrane of the myofiber, the Sarcolemma. As the AChRs open ion channels, the membrane depolarizes, causing muscle contraction. The entire synapse is sheathed within a myelin cover provided by the Schwann cell to insulate and encapsulate the junction. The NMJ is functional at birth but undergoes numerous alterations postnatally. One step in maturation is the elimination of excess inputs, a competitive process in which the muscle is an intermediary. Once elimination is complete, the NMJ is maintained stably in a dynamic equilibrium that can be perturbed to initiate remodeling.

Factors that Regulate Synaptogenesis
In recent studies, TGF-β and Glia are directly related in the regulation of synaptogenesis. For example, the absence of TGF-β ligands or glia results in fewer synapses with other neurons. This was determined when the TGF-β ligands were removed from the NMJ(neuromuscular Junction) of Drosophila melanogaster and the resulting data showed a dramatic decrease in the number of synapses. The removal of glia cells decreased the amount of TGF-β activation therefore, the number of synapses decreased. These are the few factors that effect synaptogenesis.