Synaptogenesis of the calyx of Held: rapid onset of function and one-to-one morphological innervation.

Synaptogenesis during early development is thought to follow a canonical program whereby synapses increase rapidly in number and individual axons multiply-innervate nearby targets. Typically, a subset of inputs then out-competes all others through experience-driven processes to establish stable, long-lasting contacts. We investigated the formation of the calyx of Held, probably the largest nerve terminal in the mammalian CNS. Many basic functional and morphological features of calyx growth have not been studied previously, including whether mono-innervation, a hallmark of this system in adult animals, is established early in development. Evoked postsynaptic currents, recorded from neonatal mice between postnatal day 1 (P1) and P4, increased dramatically from -0.14 +/- 0.04 nA at P1 to -6.71 +/- 0.65 nA at P4 with sharp jumps between P2 and P4. These are the first functional assays of these nascent synapses for ages less than P3. AMPA and NMDA receptor-mediated currents were prominent across this age range. Electron microscopy (EM) revealed a concomitant increase, beginning at P2, in the prevalence of postsynaptic densities (16-fold) and adhering contacts (73-fold) by P4. Therefore, both functional and structural data showed that young calyces could form within 2 d, well before the onset of hearing around P8. Convergence of developing calyces onto postsynaptic targets, indicative of competitive processes that precede mono-innervation, was rare (4 of 29) at P4 as assessed using minimal stimulation electrophysiology protocols. Serial EM sectioning through 19 P4 cells further established the paucity (2 of 19) of convergence. These data indicate that calyces of Held follow a noncanonical program to establish targeted innervation that occurs over a rapid time course and precedes auditory experience.

HPV vaccine development: A case study of prevention and politics.

An analysis of the development of human papillomavirus (HPV) vaccines requires a fundamental comprehension of the underlying science of the technology, as well as an appreciation for the business issues essential to successful commercialization. Students analyzing this topic must consider scientific challenges related to the development of these vaccines, as well as the implications for their commercialization. This case study describes the evolution of our understanding of HPV infection and its causative link to cervical cancer, the establishment of viable HPV vaccine candidates, and various issues related to HPV vaccine implementation. Study questions for use in generating class discussion are provided.