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The connectome of rostral ventrolateral medulla C1 neurons
Author(s) -
Le Sheng,
Dempsey Bowen,
Turner Anita,
Allen Andrew,
Goodchild Ann,
McMullan Simon
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1006.6
Subject(s) - rostral ventrolateral medulla , neuroscience , population , medulla , rostral ventromedial medulla , medulla oblongata , biology , connectome , anatomy , nociception , central nervous system , medicine , receptor , biochemistry , environmental health , hyperalgesia , functional connectivity
The transcription factor Phox2b is co‐expressed on a large proportion of rostral ventrolateral medulla (RVLM) sympathetic premotor neurons. This population is thought to play a key role in the transmission of vasomotor sympathetic drive and represents a major site of convergence for multiple descending and reflex pathways that co‐ordinate sympathetic nerve activity. Elucidating the organization of the circuits that control these neurons is a key research objective. Here we present brain‐wide connectomic maps of neurons that provide monosynaptic drive to RVLM C1 neurons, generated using a two‐step restricted trans‐synaptic viral tracing strategy. Phox2b expressing C1 neurons were first transduced with a lentiviral vector to express a cassette containing the cognate avian receptor TVA and rabies G‐protein. TVA‐expressing neurons were then selectively infected with a reporter‐expressing rabies variant, SADΔG (EnvA)‐RFP, which retrogradely and trans‐synaptically labelled neurons that provide monosynaptic drive to Phox2b‐positive neurons. By precisely targeting rabies injections to the core of the RVLM we were able to restrict rabies ‘seeding’ to small numbers of RVLM C1 neurons immediately caudal to the facial nucleus, and then map the locations of neurons that provide monosynaptic input to the seed population. We observed reproducible patterns of inputs arising from the dorsal, contralateral, and midline medulla, and local RVLM interneurons and neurons likely to reside within the Bötzinger, pre‐Bötzinger, and ventral respiratory groups. Distant inputs were identified in the pons and midbrain, and included previously suspected sites of monosynaptic drive such as the paraventricular nucleus of the hypothalamus.