A group of glutamatergic interneurons expressing high levels of both neurokinin-1 receptors and somatostatin identifies the region of the pre-Bötzinger complex

J Comp Neurol. 2003 Jan 20;455(4):499-512. doi: 10.1002/cne.10504.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carrier Proteins / biosynthesis
  • Carrier Proteins / genetics
  • Enkephalins / biosynthesis
  • Enkephalins / genetics
  • Glutamate Decarboxylase / biosynthesis
  • Glutamate Decarboxylase / genetics
  • Glutamic Acid / metabolism*
  • Immunohistochemistry
  • In Situ Hybridization
  • Interneurons / cytology*
  • Interneurons / metabolism
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics
  • Male
  • Membrane Transport Proteins*
  • Protein Precursors / biosynthesis
  • Protein Precursors / genetics
  • RNA, Messenger / biosynthesis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Neurokinin-1 / biosynthesis*
  • Respiratory Center / cytology*
  • Somatostatin / biosynthesis*
  • Somatostatin / genetics
  • Vesicular Glutamate Transport Protein 2
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Enkephalins
  • Isoenzymes
  • Membrane Transport Proteins
  • Protein Precursors
  • RNA, Messenger
  • Receptors, Neurokinin-1
  • Slc17a6 protein, rat
  • Vesicular Glutamate Transport Protein 2
  • Vesicular Transport Proteins
  • Glutamic Acid
  • Somatostatin
  • preproenkephalin
  • Glutamate Decarboxylase
  • glutamate decarboxylase 1