New views on synapse-glia interactions

Although glial cells ensheath synapses throughout the nervous system, the functional consequences of this relationship are uncertain. Recent studies suggest that glial cells may promote the formation of synapses and help to maintain their function by providing nerve terminals with energy substrates and glutamate precursors

Synaptic efficacy enhanced by glial cells in vitro

In the developing nervous system, glial cells guide axons to their target areas, but it is unknown whether they help neurons to establish functional synaptic connections. The role of glial cells in synapse formation and function was studied in cultures of purified neurons from the rat central nervous system. In glia-free cultures, retinal ganglion cells formed synapses with normal ultrastructure but displayed little spontaneous synaptic activity and high failure rates in evoked synaptic transmission. In cocultures with neuroglia, the frequency and amplitude of spontaneous postsynaptic currents were potentiated by 70-fold and 5-fold, respectively, and fewer transmission failures occurred. Glial cells increased the action potential-independent quantal release by 12-fold without affecting neuronal survival. Thus, developing neurons in culture form inefficient synapses that require glial signals to become fully functional

BMP Signaling in astrocytes downregulates EGFR to modulate survival and maturation

10.1371/journal.pone.0110668PLoS ONE910e11066

Characterization of the signaling interactions that promote the survival and growth of developing retinal ganglion cells in culture

The signaling mechanisms that control the survival of CNS neurons are poorly understood. Here we show that, in contrast to PNS neurons, the survival of purified postnatal rat retinal ganglion cells (RGCs) in vitro is not promoted by peptide trophic factors unless their intracellular cAMP is increased pharmacologically or they are depolarized by K+ or glutamate agonists. Long-term survival of most RGCs in culture can be promoted by a combination of trophic factors normally produced along the visual pathway, including BDNF, CNTF, IGF1, an oligodendrocyte-derived protein, and forskolin. These results suggest that neurotransmitter stimulation and electrical activity enhance the survival of developing RGCs and raise the question of whether the survival control mechanisms of PNS and CNS neurons are different

Hepatocyte growth factor/scatter factor is an axonal chemoattractant and a neurotrophic factor for spinal motor neurons

In the embryonic nervous system, developing axons can be guided to their targets by diffusible factors secreted by their intermediate and final cellular targets. To date only one family of chemoattractants for developing axons has been identified. Grafting and ablation experiments in fish, amphibians, and birds have suggested that spinal motor axons are guided to their targets in the limb in part by a succession of chemoattractants made by the sclerotome and by the limb mesenchyme, two intermediate targets that these axons encounter en route to their target muscles. Here we identify the limb mesenchyme-derived chemoattractant as hepatocyte growth factor/scatter factor (HGF/SF), a diffusible ligand for the c-Met receptor tyrosine kinase, and we also implicate HGF/SF at later stages as a muscle-derived survival factor for motoneurons. These results indicate that, in addition to functioning as a mitogen, a motogen, and a morphogen in nonneural systems, HGF/SF can function as a guidance and survival factor in the developing nervous system

Single-Cell RNA Sequencing of Lymph Node Stromal Cells Reveals Niche-Associated Heterogeneity.

Stromal cells (SCs) establish the compartmentalization of lymphoid tissues critical to the immune response. However, the full diversity of lymph node (LN) SCs remains undefined. Using droplet-based single-cell RNA sequencing, we identified nine peripheral LN non-endothelial SC clusters. Included are the established subsets, Ccl19 <sup>hi</sup> T-zone reticular cells (TRCs), marginal reticular cells, follicular dendritic cells (FDCs), and perivascular cells. We also identified Ccl19 <sup>lo</sup> TRCs, likely including cholesterol-25-hydroxylase <sup>+</sup> cells located at the T-zone perimeter, Cxcl9 <sup>+</sup> TRCs in the T-zone and interfollicular region, CD34 <sup>+</sup> SCs in the capsule and medullary vessel adventitia, indolethylamine N-methyltransferase <sup>+</sup> SCs in the medullary cords, and Nr4a1 <sup>+</sup> SCs in several niches. These data help define how transcriptionally distinct LN SCs support niche-restricted immune functions and provide evidence that many SCs are in an activated state