Nucleus magnocellularis and nucleus laminaris in the avian brainstem contain second- and third-order auditory neurons thought to be homologous to the mammalian anteroventral cochlear nucleus and medial superior olivary nucleus, respectively. Nucleus laminaris in the chicken is a tonotopically organized sheet of bipolar neurons; each of these neurons receives spatially segregated bilateral innervation from the two magnocellular nuclei. In the present study, this projection was studied at the single cell level by analyzing the pattern of terminal arborizations of individual horseradish peroxidase-filled axons. Reconstruction of the terminal arborizations of nucleus magnocellularis axons revealed that each axon forms an elongated band of endings, the long axis of which is parallel to the physiologically defined isofrequency bands. Within a band, the individual terminal collaterals form distinct patches separated by areas without endings. We suggest that the elongated terminal fields provide the basis of the tonotopic organization observed in nucleus laminaris and that the trajectories of the ipsilateral and contralateral axons may provide differential conduction delays that are important for binaural integration of acoustic information.

This study examined the development of individual axon terminal fields in n. laminaris (NL) of the chicken brainstem. In their mature form axons from the nucleus magnocellularis (NM), second-order auditory neurons in the chicken brainstem, project bilaterally onto the NL. Axons from the ipsilateral and contralateral NM neurons form spatially segregated, elongated arbors in the dorsal and ventral neuropil of NL, respectively. The long axes of these arbors correspond to physiologically defined isofrequency bands. To assess the development of this stereotyped arborization pattern, 6-17-day embryonic chicken brain stems were maintained in vitro while injecting horseradish peroxidase into small groups of axons. Three-dimensional reconstructions were made from serial sections and projected onto a cartesian plane for quantitative analyses. At embryonic day 6 (E6), the ventral axons already course beneath the recently migrated NL neurons. The arrival of the dorsal NM axon branches is delayed and their paths are indirect. They first loop dorsally into the the ventricular layer, where they seem to make specific connections with migrating NL neurons and use these as guides to their appropriate positions in the NL. During the period from E9 to E17 the dorsal and ventral terminal fields become similar, each adopting properties of the other's initial pattern. The dorsal terminal fields extend to form bands similar to the early ventral terminal fields, while the ventral terminal fields narrow and appear to shift position in order to achieve the tonotopic specificity characteristic of the early dorsal terminal fields. The results show that a complex, mature pattern of neuronal connections can be formed during development by the combination and reorganization of two simple patterns--each shaped, in turn, by its respective axonal trajectory.

Gap junctions have been postulated to exist between the axons of excitatory cortical neurons based on electrophysiological, modeling, and dye-coupling data. Here, we provide ultrastructural evidence for axoaxonic gap junctions in dentate granule cells. Using combined confocal laser scanning microscopy, thin-section transmission electron microscopy, and grid-mapped freeze-fracture replica immunogold labeling, 10 close appositions revealing axoaxonic gap junctions (Ϸ30 -70 nm in diameter) were found between pairs of mossy fiber axons (Ϸ100 -200 nm in diameter) in the stratum lucidum of the CA3b field of the rat ventral hippocampus, and one axonal gap junction (Ϸ100 connexons) was found on a mossy fiber axon in the CA3c field of the rat dorsal hippocampus. Immunogold labeling with two sizes of gold beads revealed that connexin36 was present in that axonal gap junction. These ultrastructural data support computer modeling and in vitro electrophysiological data suggesting that axoaxonic gap junctions play an important role in the generation of very fast (>70 Hz) network oscillations and in the hypersynchronous electrical activity of epilepsy.axoaxonic ͉ connexin ͉ electrical synapse ͉ epilepsy ͉ synchronization

Stimulation of group I metabotropic glutamate receptors (mGluRs) by the agonist (S)-dihydroxyphenylglycine in the hippocampus transforms normal neuronal activity into prolonged epileptiform discharges. The conversion is long lasting in that epileptiform discharges persist after washout of the inducing agonist and serves as a model of epileptogenesis. The group I mGluR model of epileptogenesis took on special significance because epilepsy associated with fragile X syndrome (FXS) may be caused by excessive group I mGluR signaling. At present, the plasticity mechanism underlying the group I mGluR-mediated epileptogenesis is unknown. I mGluR(V) , a voltagegated cationic current activated by group I mGluR agonists in CA3 pyramidal cells in the hippocampus, is a possible candidate. I mGluR(V) activation is associated with group I mGluR agonist-elicited epileptiform discharges. For I mGluR(V) to play a role in epileptogenesis, long-term activation of the current must occur after group I mGluR agonist exposure or synaptic stimulation. We observed that I mGluR(V) , once induced by group I mGluR agonist stimulation in CA3 pyramidal cells, remained undiminished for hours after agonist washout. In slices prepared from FXS model mice, repeated stimulation of recurrent CA3 pyramidal cell synapses, effective in eliciting mGluRmediated epileptiform discharges, also induced long-lasting I mGluR(V) in CA3 pyramidal cells. Similar to group I mGluR-mediated prolonged epileptiform discharges, persistent I mGluR(V) was no longer observed in preparations pretreated with inhibitors of tyrosine kinase, of extracellular signal-regulated kinase 1/2, or of mRNA protein synthesis. The results indicate that I mGluR(V) is an intrinsic plasticity mechanism associated with group I mGluR-mediated epileptogenesis.