Andrew & Patrick’s Neuroblog

Here’s some more of the important data that was in this paper by Syken et al:

1. Arc induction: Arc is an immediate early gene that is induced by recent neuronal activity. Arc mRNA can be detected via in situ hybridization for a variety of purposes, one of which is to view the area of visual cortex that represents one eye. In PirB KO mice, ocular dominance plasticity is increased and it was shown that the width of the Arc induction was greater in KO compared to wt.

The current model is that PirB is an MHCI receptor that acts to limit the extent of synaptic plasticity, possibly balancing the effects of molecules (e.g. in the MAPK signaling pathway) that enhance plasticity. PirB acts as an MHCI receptor in the immune system to affect integrin-dependent cytoskeletal dynamics, and if it does the same thing in the immune system, it could fit into the story.

In a 2000 publication, Huh et al. (http://www.ncbi.nlm.nih.gov/pubmed/11118151) demonstrated a novel role for immune molecules (MHCI, major histocompatibility complex class I) in the nervous system. In mice lacking the proper molecules for stable cell surface expression of MHCI molecules, retinogeniculate refinement is incomplete, LTP is enhanced, and LTD is absent. This was the first demonstration that MHCI molecules are important for activity-dependent development and refinement of neural circuits, and in synaptic plasticity.

Syken et al. extends this work by identifying that PirB, an MHCI receptor in the immune system, is also a neuronal receptor. They lay the groundwork, showing that PirB is present at synapses and binds to neurons in an MHCI-level-dependent manner. In an ocular dominance plasticity assay, PirB-/- mice exhibit expanded OD columns relative to wildtype following monocular enucleation - this suggests that PirB, along with associated MHCI molecules, restricts the extent of plasticity and perhaps acts to stabilize circuit

• http://www.ncbi.nlm.nih.gov/pubmed/16917027

Rockefeller scientists led by Shai Shaham found C. elegans neurons survive in the absence of glia, albeit with highly abnormal morphologies. They observed in a recent Development paper that dendrites were severely shortened and axon guidance/branching were impaired, implicating glia in brain development.

GIia removal was performed by mutating mls-2 and vab-3, genes involved in glia differentiation and expression, or by using laser microbeams to ablate glial precursors. Crucially, C. elegans glia do not exhibit trophic support of neurons and resemble vertebrate glia both morphologically and functionally, making possible in vivo studies of neural-glial roles in both the development and function of the nervous system.

• http://www.ncbi.nlm.nih.gov/pubmed/18508862

John Ngai at Berkeley’s Helen Wills Neuroscience Institute recently reported in Neuron a role for insulin-like growth factor (Igf) in the neural development of olfaction – IGF was previously established mainly as a hormone that stimulated cell proliferation.

By studying Igf1 and Igf2 mutant mice, Ngai and colleagues in China and Columbia found the disruption of IGF signaling pathways during neural development disrupted the mirror symmetry of the olfactory bulb’s sensory innervation map. Furthermore, axons targeted for the lateral olfactory bulb were misrouted to ectopic sites, suggesting a role for Igf in axon guidance. Igf was also shown, through primary neuronal cultures, to be a chemoattractant for axon growth cones; this is a new role for Igf in development and is currently being investigated further.

For further reading, see:

• http://www.ncbi.nlm.nih.gov/pubmed/18367086