Regulating Receptor Levels at a Developing Synapse

differentiation in target cells at neuron–neuron syn-and indicates that neither activity nor the previous exis-apses. However, the postsynaptic markers used in this tence of NMDA receptors at a synapse is necessary study, although good indicators of postsynaptic differ-for insertion of GluR1-containing AMPA receptors into entiation, may not be the earliest postsynaptic mole-synapses. cules to cluster at the contact. A chronological analysis In conclusion, Ziv and colleagues have elegantly de-cannot answer questions about synapse induction in signed experiments that allowed them to follow a syn-the absence of molecular candidates for this function apse from birth through its earliest stages of develop-but may be very useful in sorting out their roles once ment. This approach has provided insights into the time such molecules are found. Two recently described frame of synaptogenesis and the sequence of addition candidates that may have a role in inducing synapto-of synaptic components at glutamatergic synapses. A genesis are Narp and neuroligin. Narp (neuronal activity– similar strategy applied to other synapse types will show regulated pentraxin) is a secreted immediate-early gene whether we can generalize from these results. Future localized to both presynaptic and postsynaptic sites at studies using this strategy and combining it with post-excitatory synapses on GABAergic cells. Narp-express-synaptic imaging may lead to further exciting insights ing HEK293 cells can induce AMPA-type glutamate re-into the life and times of a synapse. ceptor clustering at extrasynaptic sites in spinal cord neurons, suggesting that Narp may induce postsynaptic Anuradha Rao and Sabine Lé vi differentiation (O'Brien et al., 1999). Neuroligins are cell Department of Anatomy and Neurobiology adhesion proteins that have been suggested to be in-into synapses with a longer time course? Further, are these 2 hr old synapses mature, and, if not, what are the further steps necessary for maturation? It would be interesting to determine the birth date of synapses and do retrospective electron microscopy to look at morphology or combine it with calcium imaging of postsyn-event at glutamatergic synapses is suggested to be the developmental conversion of synapses containing only NMDA receptors (silent synapses) to ones that contain As in any good marriage, open communication is critical both NMDA and AMPA receptors through an activity-when pre-and postsynaptic cells commit to building a driven NMDA receptor–dependent process. The use-synapse. After the initial flirtation of growth cone and fulness of their strategy is apparent from the observation target cell, the hard work of synaptogenesis begins. The of …