title: A group of glutamatergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Bötzinger complex.
abstract: The pre-Bötzinger complex (pre-BötC) is a physiologically defined group of ventrolateral medullary neurons that plays a central role in respiratory rhythm generation. These cells are located in a portion of the rostral ventrolateral medulla (RVLM) that is difficult to identify precisely for lack of a specific marker. We sought to determine whether somatostatin (SST) might be a marker for this region. The rat pre-BötC area was defined as a 500-microm-long segment of ventrolateral medulla coextensive with the ventral respiratory group. This region was identified by juxtacellular labeling of neurons with respiratory-related activity and by its location rostral to the phrenic premotor neurons. It contained most of the SST-ir neuronal somata of the RVLM. These cells were small (107 microm(2)) and expressed high levels of preprosomatostatin mRNA. They were strongly neurokinin 1 receptor (NK1R)-ir and were selectively destroyed by saporin conjugated with an NK1R agonist (SSP-SAP). Most SST-ir neurons (>90%) contained vesicular glutamate transporter 2 (VGLUT2) mRNA, and terminals immunoreactive for SST and VGLUT2 protein were found in their midst. Few SST-ir neurons contained GAD-67 mRNA (<1%) or preproenkephalin mRNA (6%). Retrograde labeling experiments demonstrated that over 75% of the SST-ir neurons project to the contralateral pre-BötC area, but none projects to the spinal cord. In conclusion, the RVLM contains many neurons that express preprosomatostatin mRNA. A subgroup of these cells contains high levels of SST and NK1R immunoreactivity in their somata. These glutamatergic interneurons identify a narrow region of the RVLM that appears to be coextensive with the pre-BötC of adult rats.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908-0735, USA. rs3j@virginia.edu
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Stornetta
authors.forename: Diane L
authors.initials: DL
authors.lastname: Rosin
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Charles P
authors.initials: CP
authors.lastname: Sevigny
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Weston
authors.forename: Patrice G
authors.initials: PG
authors.lastname: Guyenet
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000096:biosynthesis / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007395:Interneurons / Q000166:cytology* / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis*; D012125:Respiratory Center / Q000166:cytology*; D013004:Somatostatin / Q000096:biosynthesis* / Q000235:genetics; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins
chemical_list: D002352:Carrier Proteins; D004745:Enkephalins; D007527:Isoenzymes; D026901:Membrane Transport Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D018040:Receptors, Neurokinin-1; C493475:Slc17a6 protein, rat; D050599:Vesicular Glutamate Transport Protein 2; D033921:Vesicular Transport Proteins; D018698:Glutamic Acid; D013004:Somatostatin; C033660:preproenkephalin; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1