title: Hypothalamic neurotensin projections promote reward by enhancing glutamate transmission in the VTA.
abstract: The lateral hypothalamus (LH) sends a dense glutamatergic and peptidergic projection to dopamine neurons in the ventral tegmental area (VTA), a cell group known to promote reinforcement and aspects of reward. The role of the LH to VTA projection in reward-seeking behavior can be informed by using optogenetic techniques to dissociate the actions of LH neurons from those of other descending forebrain inputs to the VTA. In the present study, we identify the effect of neurotensin (NT), one of the most abundant peptides in the LH to VTA projection, on excitatory synaptic transmission in the VTA and reward-seeking behavior. Mice displayed robust intracranial self-stimulation of LH to VTA fibers, an operant behavior mediated by NT 1 receptors (Nts1) and NMDA receptors. Whole-cell patch-clamp recordings of VTA dopamine neurons demonstrated that NT (10 nm) potentiated NMDA-mediated EPSCs via Nts1. Results suggest that NT release from the LH into the VTA activates Nts1, thereby potentiating NMDA-mediated EPSCs and promoting reward. The striking behavioral and electrophysiological effects of NT and glutamate highlight the LH to VTA pathway as an important component of reward.
authors: Ernest Gallo Clinic and Research Center, Emeryville, California 94608, USA.
authors: Kimberly A
authors: KA
authors: Kempadoo
authors: Clara
authors: C
authors: Tourino
authors: Saemi L
authors: SL
authors: Cho
authors: Francesco
authors: F
authors: Magnani
authors: Gina-Marie
authors: GM
authors: Leinninger
authors: Garret D
authors: GD
authors: Stuber
authors: Feng
authors: F
authors: Zhang
authors: Martin G
authors: MG
authors: Myers
authors: Karl
authors: K
authors: Deisseroth
authors: Luis
authors: L
authors: de Lecea
authors: Antonello
authors: A
authors: Bonci
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D000075402:Channelrhodopsins; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008027:Light; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009434:Neural Pathways / Q000502:physiology; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors / Q000172:deficiency; D012201:Reward; D012653:Self Stimulation; D015398:Signal Transduction / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*
chemical_list: D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D018691:Excitatory Amino Acid Antagonists; D008164:Luminescent Proteins; D011720:Pyrazoles; D011804:Quinolines; D011810:Quinoxalines; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; C054562:yellow fluorescent protein, Bacteria; C079087:SR 48692; D009496:Neurotensin; D018698:Glutamic Acid; C056723:FG 9041; C056639:2-amino-5-phosphopentanoic acid; D014446:Tyrosine 3-Monooxygenase; D014633:Valine
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