ABSTRACT
Inhibitory neurons control the firing of glutamatergic neurons and synchronize brain activity. However, little is known about mechanisms of excitatory synapse formation in inhibitory neurons. Here we demonstrate that Erbin is specifically expressed in cortical inhibitory neurons. It localizes at excitatory synapses and regulates AMPA receptor (AMPAR) surface expression. Erbin mutation reduced mEPSCs and AMPAR currents specifically in parvalbumin (PV)-positive interneurons but not in pyramidal neurons. We found that the AMPAR auxiliary protein TARP γ-2 was specifically expressed in cortical interneurons. Erbin interacts with TARP γ-2 and is crucial for its stability. Deletion of the γ-2-interacting domain in Erbin attenuated surface AMPAR and excitatory transmission in PV-positive interneurons. Furthermore, we observed behavioral deficits in Erbin-null mice and in mice expressing an Erbin truncation mutant that is unable to interact with TARP γ-2. These observations demonstrate a crucial function for Erbin in AMPAR surface expression in cortical PV-positive interneurons and may contribute to a better understanding of psychiatric disorders.
Subject(s)
Calcium Channels/metabolism , Carrier Proteins/metabolism , Cerebral Cortex/metabolism , Interneurons/metabolism , Receptors, AMPA/metabolism , Synapses/metabolism , Animals , Behavior, Animal/physiology , Calcium Channels/genetics , Carrier Proteins/genetics , Cerebral Cortex/cytology , Excitatory Postsynaptic Potentials/physiology , HEK293 Cells , Humans , Interneurons/cytology , Intracellular Signaling Peptides and Proteins , Mice , Mice, Knockout , Miniature Postsynaptic Potentials/physiology , Motor Activity/genetics , Parvalbumins/metabolism , Receptors, AMPA/genetics , Synapses/genetics , Synaptic Transmission/genetics , gamma-Aminobutyric Acid/metabolismABSTRACT
An environmental survey of tabanid host spiroplasma carriage was undertaken at 10 collection sites in Australia during February 1999. A total of 164 tabanid flies, representing 27 species, were collected and sustainable spiroplasma isolations were made from 48 of the flies. The morphology of the cultured spiroplasmas, as observed in M1D medium under dark-field microscopy, was typical of either (i) Apis group spiroplasmas (relatively thick cells (approximately 150 nm) with six or more turns) or (ii) chrysopicola-syrphidicola-TAAS-1 clade spiroplasmas (narrower, often much shorter cells) serologically related to Spiroplasma serogroup VIII. Repetitive serological analyses, involving successive rounds of dilution cloning and serological reevaluation, identified one serotype referable to the Spiroplasma serogroup VIII strain complex and five putative members of the Apis clade. Apis clade placement for these five groups was verified using 16S rRNA phylogenetic analyses. Among the Apis clade members, one serotype representing 11 isolates was identified as a geographic variant of Spiroplasma turonicum. Spiroplasma turonicum (Tab4C) was originally isolated from a tabanid Haematopoda sp. in France. The other 34 isolates represented four new serogroups (= putative species). The following strains are proposed as representatives of the new serogroups: strain GSU5478 (group XXXIX), strain GSU5490 (group XL), strain GSU5508 (group XLI), and strain GSU5603 (group XLII). In summary, six serogroups were observed from isolations originating from seven distinct sample sites in Australia. Surprisingly, the serotype with the greatest geographical range (five sites from 16 degrees 48.9'S to 35 degrees 40.0'S) and the greatest host diversity (nine species over three genera) was the geographic variant of S. turonicum, which had only been reported previously in France.
