Synaptic inputs compete during rapid formation of the calyx of Held: a new model system for neural development.

Hallmark features of neural circuit development include early exuberant innervation followed by competition and pruning to mature innervation topography. Several neural systems, including the neuromuscular junction and climbing fiber innervation of Purkinje cells, are models to study neural development in part because they establish a recognizable endpoint of monoinnervation of their targets and because the presynaptic terminals are large and easily monitored. We demonstrate here that calyx of Held (CH) innervation of its target, which forms a key element of auditory brainstem binaural circuitry, exhibits all of these characteristics.

Maturation of synaptic partners: functional phenotype and synaptic organization tuned in synchrony.

Maturation of principal neurons of the medial nucleus of the trapezoid body (MNTB) was assessed in the context of the developmental organization and activity of their presynaptic afferents, which grow rapidly to form calyces of Held and to establish mono-innervation between postnatal days (P)2 and 4. MNTB neurons and their inputs were studied from embryonic day (E)17, when the nucleus was first discernable, until P14 after the onset of hearing. Using a novel slice preparation containing portions of the cochlea, cochlear nucleus and MNTB, we determined that synaptic inputs form onto MNTB neurons at E17 and stimulation of the cochlear nucleus can evoke action potentials (APs) and Ca(2+) signals.

Does the brain connect before the periphery can direct? A comparison of three sensory systems in mice.

The development of peripheral to central neural connections within the auditory, visual, and olfactory systems of mice is reviewed to address whether peripheral signaling may play an instructive role during initial synapse formation. For each sensory system, developmental times of histogenesis and the earliest ages of innervation and function are considered for peripheral and selected central relays. For the auditory and visual system, anatomical and functional reports indicate that central connections may form prior to synapse formation in the periphery.

Serial sectioning and electron microscopy of large tissue volumes for 3D analysis and reconstruction: a case study of the calyx of Held.

Serial section electron microscopy is typically applied to investigation of small tissue volumes encompassing subcellular structures. However, in neurobiology, the need to relate subcellular structure to organization of neural circuits can require investigation of large tissue volumes at ultrastructural resolution. Analysis of ultrastructure and three-dimensional reconstruction of even one to a few cells is time consuming, and still does not generate the necessary numbers of observations to form well-grounded insights into biological principles.

Modulation of synaptic function in retinal amacrine cells.

Amacrine cells are interneurons that have diverse functions in retinal signal processing. In order to study signaling and modulation in retinal amacrine cells, we employ a simplified culture system containing identifiable GABAergic amacrine cells. Immunocytochemistry experiments indicate that GABAergic amacrine cells express metabotropic glutamate receptor 5 (mGluR5), a group I mGluR usually linked to the IP3 signaling pathway.

Activation of mGluR5 modulates GABA(A) receptor function in retinal amacrine cells.

Amacrine cells in the vertebrate retina receive glutamatergic input from bipolar cells and make synapses onto bipolar cells, ganglion cells, and other amacrine cells. Recent studies indicate that amacrine cells express metabotropic glutamate receptors (mGluRs) and that signaling within the inner plexiform layer (IPL) of the retina might be modulated by mGluR activity. This study tests the hypothesis that activation of mGluR5 modulates GABA(A) receptor function in retinal amacrine cells.