Synapses between corticotropin‐releasing factor‐containing axon terminals and dopaminergic neurons in the ventral tegmental area are predominantly glutamatergic
- 7 December 2007
- journal article
- research article
- Published by Wiley in Journal of Comparative Neurology
- Vol. 506 (4), 616-626
- https://doi.org/10.1002/cne.21576
Abstract
Interactions between stress and the mesocorticolimbic dopamine (DA) system have been suggested from behavioral and electrophysiological studies. Because corticotropin‐releasing factor (CRF) plays a role in stress responses, we investigated possible interactions between neurons containing CRF and those producing DA in the ventral tegmental area (VTA). We first investigated the cellular distribution of CRF in the VTA by immunolabeling VTA sections with anti‐CRF antibodies and analyzing these sections by electron microscopy. We found CRF immunoreactivity present mostly in axon terminals establishing either symmetric or asymmetric synapses with VTA dendrites. We established that nearly all CRF asymmetric synapses are glutamatergic, insofar as the CRF‐immunolabeled axon terminals in these synapses coexpressed the vesicular glutamate transporter 2, and that the majority of CRF symmetric synapses are GABAergic, insofar as the CRF‐immunolabeled axon terminals in these synapses coexpressed glutamic acid decarboxylase, findings that are of functional importance. We then looked for synaptic interactions between CRF‐ and DA‐containing neurons, by using antibodies against CRF and tyrosine hydroxylase (TH; a marker for DA neurons). We found that most synapses between CRF‐immunoreactive axon terminals and TH neurons are asymmetric (in the majority likely to be glutamatergic) and suggest that glutamatergic neurons containing CRF may be part of the neuronal circuitry that mediates stress responses involving the mesocorticolimbic DA system. The presence of CRF synapses in the VTA offers a mechanism for interactions between the stress‐associated neuropeptide CRF and the mesocorticolimbic DA system. J. Comp. Neurol. 506:616–626, 2008. Published 2007 Wiley‐Liss, Inc.Keywords
This publication has 41 references indexed in Scilit:
- The Functional Neuroanatomy of Corticotropin‐Releasing FactorCiba Foundation symposium, 2007
- Effects of arousal‐ and feeding‐related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the ratEuropean Journal of Neuroscience, 2006
- Effects of arousal‐ and feeding‐related neuropeptides on dopaminergic and GABAergic neurons in the ventral tegmental area of the ratEuropean Journal of Neuroscience, 2006
- Dopamine, learning and motivationNature Reviews Neuroscience, 2004
- Brain Reward Circuitry: Insights from Unsensed IncentivesNeuron, 2002
- GFRα‐1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental areaJournal of Comparative Neurology, 2001
- The neural basis of drug craving: An incentive-sensitization theory of addictionBrain Research Reviews, 1993
- Dopamine transmission in the initiation and expression of drug- and stress-induced sensitization of motor activityBrain Research Reviews, 1991
- Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses?Brain Research Reviews, 1990
- Organization of Ovine Corticotropin-Releasing Factor Immunoreactive Cells and Fibers in the Rat Brain: An Immunohistochemical StudyNeuroendocrinology, 1983