Induction of dendritic spines by an extracellular domain of AMPA receptor subunit GluR2

Synaptic transmission from excitatory nerve cells in the mammalian brain is largely mediated by AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)-type glutamate receptors located at the surface of dendritic spines. The abundance of postsynaptic AMPA receptors correlates with the size of the synapse and the dimensions of the dendritic spine head. Moreover, long-term potentiation is associated with the formation of dendritic spines as well as synaptic delivery of AMPA receptors. The molecular mechanisms that coordinate AMPA receptor delivery and spine morphogenesis are unknown. Here we show that overexpression of the glutamate receptor 2 (GluR2) subunit of AMPA receptors increases spine size and density in hippocampal neurons, and more remarkably, induces spine formation in GABA-releasing interneurons that normally lack spines. The extracellular N-terminal domain (NTD) of GluR2 is responsible for this effect, and heterologous fusion proteins of the NTD of GluR2 inhibit spine morphogenesis. We propose that the NTD of GluR2 functions at the cell surface as part of a receptor-ligand interaction that is important for spine growth and/or stability.     

A uniquely specialized ear in a very early tetrapod

The Late Devonian genus Ichthyostega was for many decades the earliest known tetrapod, and the sole representative of a transitional form between a fish and a land vertebrate. However, despite being known since 1932 (ref. 1) from a large collection of specimens, its morphology remained enigmatic and not what was expected of a very primitive tetrapod. Its apparent specializations led it to be considered as a "blind offshoot" or "sidebranch" off the tetrapod family tree, and recent cladistic analyses have disagreed about its exact phylogenetic position within the tetrapod stem group. In particular, its braincase and ear region defied interpretation, such that conventional anatomical terms seemed inapplicable. Using new material collected in 1998 (ref. 9), preparation of earlier-collected material, and high-resolution computed tomography scanning, here we identify and interpret these problematic anatomical structures. They can now be seen to form part of a highly specialized ear, probably a hearing device for use in water. This represents a structurally and functionally unique modification of the tetrapod otic region, unlike anything seen in subsequent tetrapod evolution. The presence of deeply grooved gill bars as in its contemporary Acanthostega suggest that Ichthyostega may have been more aquatically adapted than previously believed.