A genetically specified connectomics approach applied to long-range feeding regulatory circuits

Deniz Atasoy; J Nicholas Betley; Wei-Ping Li; Helen H Su; Sinem M Sertel; Louis K Scheffer; Julie H Simpson; Richard D Fetter; Scott M Sternson

doi:10.1038/nn.3854

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A genetically specified connectomics approach applied to long-range feeding regulatory circuits

Journal article

Peer reviewed

A genetically specified connectomics approach applied to long-range feeding regulatory circuits

Deniz Atasoy, J Nicholas Betley, Wei-Ping Li, Helen H Su, Sinem M Sertel, Louis K Scheffer, Julie H Simpson, Richard D Fetter and Scott M Sternson

Nature neuroscience, Vol.17(12), pp.1830-1839

12/2014

DOI: 10.1038/nn.3854

PMCID: PMC4292906

PMID: 25362474

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Abstract

Synaptic connectivity and molecular composition provide a blueprint for information processing in neural circuits. Detailed structural analysis of neural circuits requires nanometer resolution, which can be obtained with serial-section electron microscopy. However, this technique remains challenging for reconstructing molecularly defined synapses. We used a genetically encoded synaptic marker for electron microscopy (GESEM) based on intra-vesicular generation of electron-dense labeling in axonal boutons. This approach allowed the identification of synapses from Cre recombinase-expressing or GAL4-expressing neurons in the mouse and fly with excellent preservation of ultrastructure. We applied this tool to visualize long-range connectivity of AGRP and POMC neurons in the mouse, two molecularly defined hypothalamic populations that are important for feeding behavior. Combining selective ultrastructural reconstruction of neuropil with functional and viral circuit mapping, we characterized some basic features of circuit organization for axon projections of these cell types. Our findings demonstrate that GESEM labeling enables long-range connectomics with molecularly defined cell types.

Amino Acid Sequence

Animals, Genetically Modified

Mice, Inbred C57BL

Molecular Sequence Data

Male

Mice, Transgenic

Mice, 129 Strain

Nerve Net - physiology

Feeding Behavior - physiology

Animals

Photic Stimulation - methods

Time Factors

Connectome - methods

Mice

Drosophila melanogaster

Organ Culture Techniques

Details

Title: Subtitle: A genetically specified connectomics approach applied to long-range feeding regulatory circuits
Creators: Deniz Atasoy - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
J Nicholas Betley - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Wei-Ping Li - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Helen H Su - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Sinem M Sertel - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Louis K Scheffer - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Julie H Simpson - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Richard D Fetter - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Scott M Sternson - Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA
Resource Type: Journal article
Publication Details: Nature neuroscience, Vol.17(12), pp.1830-1839
DOI: 10.1038/nn.3854
PMID: 25362474
PMCID: PMC4292906
NLM abbreviation: Nat Neurosci
ISSN: 1097-6256
eISSN: 1546-1726
Publisher: United States
Grant note: P40RR018604 / NCRR NIH HHS Howard Hughes Medical Institute
Language: English
Date published: 12/2014
Academic Unit: Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
Record Identifier: 9984040255502771

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