Distinct types of GABAergic interneurons target different subcellular domains of pyramidal cells, thereby shaping pyramidal cell activity patterns. Whether the presynaptic heterogeneity of GABAergic ...innervation is mirrored by specific postsynaptic factors is largely unexplored. Here we show that dystroglycan, a protein responsible for the majority of congenital muscular dystrophies when dysfunctional, has a function at postsynaptic sites restricted to a subset of GABAergic interneurons. Conditional deletion of Dag1, encoding dystroglycan, in pyramidal cells caused loss of CCK-positive basket cell terminals in hippocampus and neocortex. PV-positive basket cell terminals were unaffected in mutant mice, demonstrating interneuron subtype-specific function of dystroglycan. Loss of dystroglycan in pyramidal cells had little influence on clustering of other GABAergic postsynaptic proteins and of glutamatergic synaptic proteins. CCK-positive terminals were not established at P21 in the absence of dystroglycan and were markedly reduced when dystroglycan was ablated in adult mice, suggesting a role for dystroglycan in both formation and maintenance of CCK-positive terminals. The necessity of neuronal dystroglycan for functional innervation by CCK-positive basket cell axon terminals was confirmed by reduced frequency of inhibitory events in pyramidal cells of dystroglycan-deficient mice and further corroborated by the inefficiency of carbachol to increase IPSC frequency in these cells. Finally, neurexin binding seems dispensable for dystroglycan function because knock-in mice expressing binding-deficient T190M dystroglycan displayed normal CCK-positive terminals. Together, we describe a novel function of dystroglycan in interneuron subtype-specific trans-synaptic signaling, revealing correlation of presynaptic and postsynaptic molecular diversity.
Dystroglycan, an extracellular and transmembrane protein of the dystrophin-glycoprotein complex, is at the center of molecular studies of muscular dystrophies. Although its synaptic distribution in cortical brain regions is long established, function of dystroglycan in the synapse remained obscure. Using mice that selectively lack neuronal dystroglycan, we provide evidence that a subset of GABAergic interneurons requires dystroglycan for formation and maintenance of axonal terminals on pyramidal cells. As such, dystroglycan is the first postsynaptic GABAergic protein for which an interneuron terminal-specific function could be shown. Our findings also offer a new perspective on the mechanisms that lead to intellectual disability in muscular dystrophies without associated brain malformations.
The South Pacific Gyre (SPG) covers 10% of the ocean's surface and is often regarded as a marine biological desert. To gain an on-site overview of the remote, ultraoligotrophic microbial community of ...the SPG, we developed a novel onboard analysis pipeline, which combines next-generation sequencing with fluorescence
hybridization and automated cell enumeration. We tested the pipeline during the SO-245 "UltraPac" cruise from Chile to New Zealand and found that the overall microbial community of the SPG was highly similar to those of other oceanic gyres. The SPG was dominated by 20 major bacterial clades, including SAR11, SAR116, the AEGEAN-169 marine group, SAR86,
, SAR324, SAR406, and SAR202. Most of the bacterial clades showed a strong vertical (20 m to 5,000 m), but only a weak longitudinal (80°W to 160°W), distribution pattern. Surprisingly, in the central gyre,
, the dominant photosynthetic organism, had only low cellular abundances in the upper waters (20 to 80 m) and was more frequent around the 1% irradiance zone (100 to 150 m). Instead, the surface waters of the central gyre were dominated by the SAR11, SAR86, and SAR116 clades known to harbor light-driven proton pumps. The alphaproteobacterial AEGEAN-169 marine group was particularly abundant in the surface waters of the central gyre, indicating a potentially interesting adaptation to ultraoligotrophic waters and high solar irradiance. In the future, the newly developed community analysis pipeline will allow for on-site insights into a microbial community within 35 h of sampling, which will permit more targeted sampling efforts and hypothesis-driven research.
The South Pacific Gyre, due to its vast size and remoteness, is one of the least-studied oceanic regions on earth. However, both remote sensing and
measurements indicated that the activity of its microbial community contributes significantly to global biogeochemical cycles. Presented here is an unparalleled investigation of the microbial community of the SPG from 20- to 5,000-m depths covering a geographic distance of ∼7,000 km. This insight was achieved through the development of a novel onboard analysis pipeline, which combines next-generation sequencing with fluorescence
hybridization and automated cell enumeration. The pipeline is well comparable to onshore systems based on the Illumina platforms and yields microbial community data in less than 35 h after sampling. Going forward, the ability to gain on-site knowledge of a remote microbial community will permit hypothesis-driven research, through the generation of novel scientific questions and subsequent additional targeted sampling efforts.
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