Optogenetic activation of GABAergic neurons in the nucleus accumbens decreases the activity of the ventral pallidum and the expression of cocaine-context-associated memory.
GABAergic medium-sized spiny neurons (MSNs) in the nucleus accumbens (NAc) differentially express D1 and D2 dopamine receptors. Both D2- and D1-MSNs in the NAc form projections into the ventral pallidum, whereas only D1-MSNs directly project into midbrain neurons. They are critical in rewarding and aversive learning, and understanding the function of these NAc efferents and the alteration of their targeted brain regions in responding to a reward-associated context is important. In this study, we activated the GABAergic neurons in the NAc of mice expressing channelrhodopsin-2 under the control of the vesicular GABA transporter promoter by an optogenetic approach, and examined its effects on the expression of cocaine-context-associated memory. In vivo optogenetic activation of the NAc GABAergic neurons inhibited the expression of cocaine-conditioned place preference (CPP). When tested 24 h later, these mice exhibited normal cocaine-induced CPP, indicating that the inhibitory effect on the expression of CPP was transient and reversible. Activation of the NAc GABAergic neurons also attenuated the learning of cocaine-induced reinforcement, as indicated by the results of behavioural sensitization. To explore how the cocaine-context-associated information was processed and integrated, we assessed the activity of NAc MSN-targeted brain nuclei and found that the activation of NAc GABAergic neurons during CPP expression resulted in a decrease of c-Fos+ cells in the ventral palladium. Our data suggested that the NAc GABAergic efferents inhibit the ventral palladium activity and negatively regulate the expression of motivational effects induced by cocaine-context-associated cues.
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Li
L
Wang
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Minjie
M
Shen
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Yongchun
Y
Yu
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Yezheng
Y
Tao
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Ping
P
Zheng
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Feifei
F
Wang
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, School of Basic Medical Sciences and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Lan
L
Ma
D017109:Akathisia, Drug-Induced / Q000503:physiopathology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001479:Basal Ganglia / Q000187:drug effects / Q000502:physiology*; D000075402:Channelrhodopsins; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D062308:Optogenetics; D011401:Promoter Regions, Genetic; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012054:Reinforcement, Psychology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics
D001426:Bacterial Proteins; D000075402:Channelrhodopsins; D018765:Dopamine Uptake Inhibitors; D008164:Luminescent Proteins; D016760:Proto-Oncogene Proteins c-fos; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C492244:Viaat protein, mouse; C054562:yellow fluorescent protein, Bacteria; D003042:Cocaine