[Abstract Title]. - Society for Neuroscience

Abstract: Astrocytes play active roles in brain physiology by dynamic interactions with neurons.
Numerous astroglial properties are thought to regulate neurotransmission, but the detailed
mechanisms remain unclear. Here we show that connexin30 (Cx30), one of the two main gap
junction proteins expressed in mature astrocytes, modulates hippocampal synaptic transmission
in CA1 pyramidal neurons. Field excitatory postsynaptic potentials are reduced in Cx30-/- mice,
compared to wild type animals. Reduced glutamatergic transmission is neither due to altered
intrinsic properties and excitability of CA1 pyramidal neurons nor postsynaptic receptor density.
It is rather due to a decrease in glutamate synaptic concentration, as the frequency but not the
amplitude of mEPSCs is reduced in Cx30-/- mice and the ratio of AMPA to NMDA synaptic
currents is unchanged. This effect is specific to glutamatergic transmission of CA1 pyramidal
cells, as miniature IPSCs of pyramidal cells, as well as mEPSCs of interneurons, are not affected
in Cx30-/- mice. Cx30 plays also a role in short and long-term synaptic plasticity, as paired-pulse
facilitation is increased, whereas post-tetanic and long-term potentiation are reduced in Cx30-/-
mice. Cx30 regulation of neurotransmission is due to reduced synaptic glutamate levels, as
demonstrated by experiments with gamma-DGG, a low affinity AMPA receptor antagonist.
Therefore glutamate clearance was assessed by measuring synaptically-evoked glutamate
transporter currents in astrocytes, which are increased by ~100% in Cx30-/- mice. In addition,
reduction of astroglial glutamate transporter currents to wild-type levels by dihydrokainate, a
specific inhibitor of GLT-1, restores normal excitatory transmission in Cx30-/- mice. Altogether
these results demonstrate that astrocytic Cx30 controls synaptic strength of excitatory terminals
by regulating glutamate clearance.
Disclosures: U. Pannasch, None; P. Ezan, None; E. Brouillet, None; K. Willecke, None; C.
Giaume, None; N. Rouach, None.
Poster
243. Abeta Assembly and Deposition
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 243.1/J7
Topic: C.01.b. Abeta assembly and deposition
Support: NIH AG00538
Larry C. Hillblom Foundation
Title: Fibrillar oligomers are a distinct neurotoxic subset of soluble amyloid beta
Authors: *J. W. WU, L. BREYDO, Y. G. KUZNETSOV, C. G. GLABE;
MB&B, Univ. of California, Irvine, Irvine, CA