Glia control experience-dependent plasticity in an olfactory critical period.

Sensory experience during developmental critical periods has lifelong consequences for circuit function and behavior, but the molecular and cellular mechanisms through which experience causes these changes are not well understood. The Drosophila antennal lobe houses synapses between olfactory sensory neurons (OSNs) and downstream projection neurons (PNs) in stereotyped glomeruli. Many glomeruli exhibit structural plasticity in response to early-life odor exposure, indicating a general sensitivity of the fly olfactory circuitry to early sensory experience.

Early Draper-mediated glial refinement of neuropil architecture and synapse number in the Drosophila antennal lobe.

Glial phagocytic activity refines connectivity, though molecular mechanisms regulating this exquisitely sensitive process are incompletely defined. We developed the Drosophila antennal lobe as a model for identifying molecular mechanisms underlying glial refinement of neural circuits in the absence of injury. Antennal lobe organization is stereotyped and characterized by individual glomeruli comprised of unique olfactory receptor neuronal (ORN) populations.

Divergent signaling requirements of dSARM in injury-induced degeneration and developmental glial phagocytosis.

Elucidating signal transduction mechanisms of innate immune pathways is essential to defining how they elicit distinct cellular responses. Toll-like receptors (TLR) signal through their cytoplasmic TIR domains which bind other TIR domain-containing adaptors. dSARM/SARM1 is one such TIR domain adaptor best known for its role as the central axon degeneration trigger after injury.

Pyroptosis Takes Aim at Neurodevelopment.

In a recent issue of Nature, Lammert et al. demonstrate that DNA damage drives AIM2-mediated pyroptosis during normal brain development, preventing anxiety-like behaviors acquisition in adults and revealing an important role for non-apoptotic mechanisms of cell death during neurodevelopment.

Dying Neurons Utilize Innate Immune Signaling to Prime Glia for Phagocytosis during Development.

Glia continuously survey neuronal health during development, providing trophic support to healthy neurons while rapidly engulfing dying ones. These diametrically opposed functions necessitate a foolproof mechanism enabling glia to unambiguously identify those neurons to support versus those to engulf. To ensure specificity, glia are proposed to interact with dying neurons via a series of carefully choreographed steps.

Focal adhesion molecules regulate astrocyte morphology and glutamate transporters to suppress seizure-like behavior.

Astrocytes are important regulators of neural circuit function and behavior in the healthy and diseased nervous system. We screened for molecules in astrocytes that modulate neuronal hyperexcitability and identified multiple components of focal adhesion complexes (FAs). Depletion of astrocytic Tensin, β-integrin, Talin, focal adhesion kinase (FAK), or matrix metalloproteinase 1 (Mmp1), resulted in enhanced behavioral recovery from genetic or pharmacologically induced seizure.

The secreted neurotrophin Spätzle 3 promotes glial morphogenesis and supports neuronal survival and function.

Most glial functions depend on establishing intimate morphological relationships with neurons. Significant progress has been made in understanding neuron-glia signaling at synaptic and axonal contacts, but how glia support neuronal cell bodies is unclear. Here we explored the growth and functions of cortex glia (which associate almost exclusively with neuronal cell bodies) to understand glia-soma interactions.

Axon Death Pathways Converge on Axundead to Promote Functional and Structural Axon Disassembly.

Axon degeneration is a hallmark of neurodegenerative disease and neural injury. Axotomy activates an intrinsic pro-degenerative axon death signaling cascade involving loss of the NAD biosynthetic enzyme Nmnat/Nmnat2 in axons, activation of dSarm/Sarm1, and subsequent Sarm-dependent depletion of NAD. Here we identify Axundead (Axed) as a mediator of axon death.

Biological constraints limit the use of rapamycin-inducible FKBP12-Inp54p for depleting PIP2 in dorsal root ganglia neurons.

Background: Rapamycin-induced translocation systems can be used to manipulate biological processes with precise temporal control. These systems are based on rapamycin-induced dimerization of FK506 Binding Protein 12 (FKBP12) with the FKBP Rapamycin Binding (FRB) domain of mammalian target of rapamycin (mTOR). Here, we sought to adapt a rapamycin-inducible phosphatidylinositol 4,5-bisphosphate (PIP2)-specific phosphatase (Inp54p) system to deplete PIP2 in nociceptive dorsal root ganglia (DRG) neurons.

The effect of cAMP signaling on the longitudinal extension of spinal sensory neurons in the chicken embryo.

Developing sensory axons grow into the spinal cord in a three-step process: the axons extend toward and into the cord, then branch rostrally and caudally to establish a longitudinal pathway, and finally grow into the grey matter. This study investigated regulation by cAMP of the longitudinal extension of this pathway within the spinal cord. The cAMP pathway was pharmacologically altered in chicken embryos to determine its effects on the establishment of the longitudinal extension of the dorsal funiculus.