A cellular and regulatory map of the cholinergic nervous system of C. elegans
Laura Pereira,
Paschalis Kratsios,
Esther Serrano-Saiz,
Hila Sheftel,
Avi E Mayo,
David H Hall,
John G White,
Brigitte LeBoeuf,
L Rene Garcia,
Uri Alon,
Oliver Hobert
Affiliations
Laura Pereira
Department of Biological Sciences, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States; Howard Hughes Medical Institute, Columbia University, New York, United States
Paschalis Kratsios
Department of Biological Sciences, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States; Howard Hughes Medical Institute, Columbia University, New York, United States
Esther Serrano-Saiz
Department of Biological Sciences, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States; Howard Hughes Medical Institute, Columbia University, New York, United States
Hila Sheftel
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Department of Neuroscience, Albert Einstein College of Medicine, New York, United States
John G White
MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
Brigitte LeBoeuf
Department of Biology, Texas A&M University, College Station, United States
L Rene Garcia
Department of Biology, Texas A&M University, College Station, United States; Howard Hughes Medical Institute, Texas A&M University, College Station, United States
Uri Alon
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel
Department of Biological Sciences, Columbia University, New York, United States; Department of Biochemistry and Molecular Biophysics, Columbia University, New York, United States; Howard Hughes Medical Institute, Columbia University, New York, United States
Nervous system maps are of critical importance for understanding how nervous systems develop and function. We systematically map here all cholinergic neuron types in the male and hermaphrodite C. elegans nervous system. We find that acetylcholine (ACh) is the most broadly used neurotransmitter and we analyze its usage relative to other neurotransmitters within the context of the entire connectome and within specific network motifs embedded in the connectome. We reveal several dynamic aspects of cholinergic neurotransmitter identity, including a sexually dimorphic glutamatergic to cholinergic neurotransmitter switch in a sex-shared interneuron. An expression pattern analysis of ACh-gated anion channels furthermore suggests that ACh may also operate very broadly as an inhibitory neurotransmitter. As a first application of this comprehensive neurotransmitter map, we identify transcriptional regulatory mechanisms that control cholinergic neurotransmitter identity and cholinergic circuit assembly.
