Present address: Department of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Rm 212, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons
Article first published online: 11 SEP 2008
© The Authors (2008). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 28, Issue 8, pages 1545–1556, October 2008
How to Cite
Borgland, S. L., Storm, E. and Bonci, A. (2008), Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons. European Journal of Neuroscience, 28: 1545–1556. doi: 10.1111/j.1460-9568.2008.06397.x
- Issue published online: 14 OCT 2008
- Article first published online: 11 SEP 2008
- Received 12 November 2007, revised 11 June 2008, accepted 4 July 2008
- orexin B;
The orexins (hypocretins) play a crucial role in arousal, feeding and reward. Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward. Orexin A/hypocretin 1 (oxA/hcrt-1) can enable long-term changes associated with drugs of abuse; however, the effects of orexin B/hypocretin 2 (oxB/hcrt-2) on excitatory synaptic transmission in the VTA are unknown. We used whole-cell patch-clamp electrophysiology in rat horizontal midbrain slices to examine the effects of oxB/hcrt-2 on excitatory synaptic transmission. We observed that oxB/hcrt-2 has distinct effects from oxA/hcrt-1 in the VTA. oxB/Hcrt-2 (100 nm) increased presynaptic glutamate release in addition to a postsynaptic potentiation of NMDA receptors (NMDARs). The oxB/hcrt-2-mediated postsynaptic potentiation of NMDARs was mediated via activation of orexin/hypocretin 2 (OX2/Hcrt-2) receptors and protein kinase C (PKC). Furthermore, the increase in transmitter release probability was also PKC-dependent, but not through activation of orexin/hypocretin 1 (OX1/Hcrt-1) or OX2/Hcrt-2 receptors. Finally, oxB/hcrt-2 or the selective OX2/Hcrt-2 receptor agonist ala11-d-leu15-orexin B, significantly reduced spike-timing-induced long-term potentiation. Taken together, these results support a dual role for oxB/hcrt-2 in mediating enhanced glutamatergic transmission in the VTA, and suggest that oxA/hcrt-1 and oxB/hcrt-2 exert different functional roles in modulating the enhancement of the motivational components of arousal and feeding.