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Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons
Author(s) -
Borgland S. L.,
Storm E.,
Bonci A.
Publication year - 2008
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2008.06397.x
Subject(s) - orexin , ventral tegmental area , lateral hypothalamus , neuroscience , long term potentiation , glutamatergic , neurotransmission , postsynaptic potential , orexin receptor , chemistry , orexin a , excitatory postsynaptic potential , dopamine , medicine , endocrinology , glutamate receptor , receptor , neuropeptide , hypothalamus , biology , dopaminergic , inhibitory postsynaptic potential
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 n m ) 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 ala 11 ‐ d ‐leu 15 ‐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.