Orexin-A increases cell surface expression of AMPA receptors in the striatum.
Accumulating evidence suggests that orexin signaling is involved in reward and motivation circuit functions. However, the underlying mechanisms are not yet fully understood. Here, we show that orexin-A potentiates AMPAR-mediated synaptic transmission in the striatum, possibly by regulating the surface expression of AMPARs. Primary culture of striatal neurons revealed increased surface expression of AMPARs following orexin-A treatment. The increase in surface-expressed AMPARs induced by orexin-A treatment was dependent on both ERK activation and the presence of extracellular Ca(2+). In the corticostriatal synapses of rat brain slices, orexin-A bath-application caused a delayed increase in the AMPAR/NMDAR EPSC ratio, suggesting that orexin-A sets in motion a series of events that lead to functional alterations in the striatal circuits. Our findings provide a potential link between the activation of orexin signaling in the striatum in response to addictive substances and neural adaptations in the reward circuitry that may mediate the long-lasting addiction-related behaviors.
Shin
Hyun Sung
HS
School of Life sciences and Biotechnology, Korea University, Anam-dong 5-ga, Seongbuk-du, Seoul 136-701, Republic of Korea.
Cho
Hyeong Seok
HS
Sung
Ki-Wug
KW
Yoon
Bong-June
BJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D009479:Neuropeptides / Q000494:pharmacology / Q000502:physiology*; D000068797:Orexins; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000096:biosynthesis*; D009435:Synaptic Transmission
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D018091:Receptors, AMPA; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium