Neuronal somata and extrasomal compartments play distinct roles during synapse formation between Lymnaea neurons.

Proper synapse formation is pivotal for all nervous system functions. However, the precise mechanisms remain elusive. Moreover, compared with the neuromuscular junction, steps regulating the synaptogenic program at central cholinergic synapses remain poorly defined. In this study, we identified different roles of neuronal compartments (somal vs extrasomal) in chemical and electrical synaptogenesis. Specifically, the electrically synapsed Lymnaea pedal dorsal A cluster neurons were used to study electrical synapses, whereas chemical synaptic partners, visceral dorsal 4 (presynaptic, cholinergic), and left pedal dorsal 1 (LPeD1; postsynaptic) were explored for chemical synapse formation. Neurons were cultured in a soma-soma or soma-axon configuration and synapses explored electrophysiologically. We provide the first direct evidence that electrical synapses develop in a soma-soma, but not soma-axon (removal of soma) configuration, indicating the requirement of gene transcription regulation in the somata of both synaptic partners. In addition, the soma-soma electrical coupling was contingent upon trophic factors present in Lymnaea brain-conditioned medium. Further, we demonstrate that chemical (cholinergic) synapses between soma-soma and soma-axon pairs were indistinguishable, with both exhibiting a high degree of contact site and target cell type specificity. We also provide direct evidence that presynaptic cell contact-mediated, clustering of postsynaptic cholinergic receptors at the synaptic site requires transmitter-receptor interaction, receptor internalization, and a protein kinase C-dependent lateral migration toward the contact site. This study provides novel insights into synaptogenesis between central neurons revealing both distinct and synergistic roles of cell-cell signaling and extrinsic trophic factors in executing the synaptogenic program.

Synapse formation and plasticity: the roles of local protein synthesis.

From simple reflexes in lower animals to complex motor patterns and learning and memory in higher animals, all nervous system functions hinge upon fundamental, albeit specialized, neuronal units termed synapses. The term synapse denotes the structural and functional building block upon which pivots the enormous information-processing capabilities of our brain. It is the neuronal communications through synapses that ultimately determine who we are and how we react and adapt to our ever-changing environment. Synapses are not only the epic center of our intellect, but they also control myriad traits of our personality, ranging from sinfulness to sainthood (see, e.g., Hamer 2004). Simply put-we are what our synapses deem us to be (LeDoux 2003)! Notwithstanding the reasoning that some aspects of the synaptic arrangement may be genetically hardwired, an overwhelming body of knowledge does nevertheless provide ample plausible evidence that synapses are highly plastic entities undergoing rapid adaptive changes throughout life. It is this adaptability that endows our brain with its "uncanny" powers.