Serotonergic inputs to FoxP2 neurons of the pre-locus coeruleus and parabrachial nuclei that project to the ventral tegmental area

Neuroscience. 2011 Oct 13;193:229-40. doi: 10.1016/j.neuroscience.2011.07.008. Epub 2011 Jul 18.


The present study demonstrates that serotonin (5-hydroxytryptamine, 5-HT)-containing axons project to two sets of neurons in the dorsolateral pons that have been implicated in salt appetite regulation. These two neuronal groups are the pre-locus coeruleus (pre-LC) and a region in the parabrachial nucleus termed the external lateral-inner subdivision (PBel-inner). Neurons in both regions constitutively express the transcription factor Forkhead protein2 (FoxP2), and become c-Fos activated after prolonged sodium depletion. They send extensive projections to the midbrain and forebrain, including a strong projection to the ventral tegmental area (VTA)-a reward processing site. The retrograde neuronal tracer cholera toxin β-subunit (CTb) was injected into the VTA region; this was done to label the cell bodies of the pre-LC and PBel-inner neurons. After 1 week, the rats were killed and their brainstems processed by a triple-color immunofluorescence procedure. The purpose was to determine whether the CTb-labeled pre-LC and PBel-inner neurons, which also had FoxP2 immunoreactive nuclei, received close contacts from 5-HT axons. Neurons with these properties were found in both sites. Since the origin of this 5-HT input was unknown, a second set of experiments was carried out in which CTb was injected into the pre-LC or lateral PB. One week later, the rats were perfused and the brainstems from these animals were analyzed for the presence of neurons that co-contained CTb and tryptophan hydroxylase (synthetic enzyme for 5-HT) immunoreactivity. Co-labeled neurons were found mainly in the area postrema and to a lesser degree, in the dorsal raphe nucleus. We propose that the 5-HT inputs to the pre-LC and PBel-inner may modulate the salt appetite-related functions that influence the reward system.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Area Postrema / cytology*
  • Cholera Toxin / metabolism
  • Female
  • Forkhead Transcription Factors / metabolism*
  • Locus Coeruleus / cytology*
  • Male
  • Neural Pathways / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Serotonergic Neurons / physiology*
  • Serotonin / metabolism*
  • Ventral Tegmental Area / physiology*


  • Forkhead Transcription Factors
  • Foxp2 protein, rat
  • Serotonin
  • Cholera Toxin