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Behavioral/Systems/Cognitive Orexin/Hypocretin Modulates Response of Ventral

Summary: Behavioral/Systems/Cognitive
Orexin/Hypocretin Modulates Response of Ventral
Tegmental Dopamine Neurons to Prefrontal Activation:
Diurnal Influences
David E. Moorman and Gary Aston-Jones
Department of Neurosciences, Medical University of South Carolina, Charleston, South Carolina 29425
Recent studies show that glutamate and orexin (ORX, also known as hypocretin) inputs to the ventral tegmental area (VTA) dopamine
(DA) cell region are essential for conditioned behavioral responses to reward-associated stimuli. In vitro experiments showed that ORX
inputs to VTA potentiate responses of DA neurons to glutamate inputs, but it has remained unclear which glutamate inputs are modu-
lated by ORX. The medial prefrontal cortex (mPFC) is a good candidate, given its role in processing complex stimulus­response infor-
mation and its reciprocal connections with VTA DA neurons. Here we used in vivo recordings in anesthetized rats to investigate the
responses of VTA DA neurons to mPFC stimulation, and how these responses are modulated by ORX. We demonstrate that mPFC
stimulation evokes short- and long-latency excitation and inhibition in DA neurons. Maximal short-latency excitatory responses origi-
nated from stimulation sites in ventral prelimbic/infralimbic cortex, and were significantly more frequent during the active than during
the rest period of the diurnal cycle. Application of ORX onto VTA DA neurons increased baseline activity and augmented or revealed
excitatory responses to mPFC stimulation independent of changes in baseline activity, and without consistently affecting inhibitory
responses. Moreover, orexin-1 receptor antagonism decreased tonic DA cell activity in active- but not rest-period animals, confirming a
diurnal influence of ORX. These results indicate that ORX potently influences DA neuron activity, in part by modulating responses to
mPFC inputs. By regulating prefrontal control of DA release, ORX projections to VTA may shape motivated behaviors in response to
conditioned stimuli.


Source: Aston-Jones, Gary - Department of Neurosciences, Medical University of South Carolina


Collections: Biology and Medicine