TY - JOUR
T1 - Aversive behavior induced by optogenetic inactivation of ventral tegmental area dopamine neurons is mediated by dopamine D2 receptors in the nucleus accumbens
AU - Danjo, Teruko
AU - Yoshimi, Kenji
AU - Funabiki, Kazuo
AU - Yawata, Satoshi
AU - Nakanishi, Shigetada
PY - 2014/4/29
Y1 - 2014/4/29
N2 - Contributed by Shigetada Nakanishi, March 23, 2014 (sent for review January 24, 2014) Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for controlling both rewarding and aversive behaviors. The transient silencing of DA neurons is one of the responses to aversive stimuli, but its consequences and neural mechanisms regarding aversive responses and learning have largely remained elusive. Here, we report that optogenetic inactivation of VTA DA neurons promptly down-regulated DA levels and induced upregulation of the neural activity in the nucleus accumbens (NAc) as evaluated by Fos expression. This optogenetic suppression of DA neuron firing immediately evoked aversive responses to the previously preferred dark room and led to aversive learning toward the optogenetically conditioned place. Importantly, this place aversion was abolished by knockdown of dopamine D2 receptors but not by that of D1 receptors in the NAc. Silencing of DA neurons in the VTA was thus indispensable for inducing aversive responses and learning through dopamine D2 receptors in the NAc.
AB - Contributed by Shigetada Nakanishi, March 23, 2014 (sent for review January 24, 2014) Dopamine (DA) transmission from the ventral tegmental area (VTA) is critical for controlling both rewarding and aversive behaviors. The transient silencing of DA neurons is one of the responses to aversive stimuli, but its consequences and neural mechanisms regarding aversive responses and learning have largely remained elusive. Here, we report that optogenetic inactivation of VTA DA neurons promptly down-regulated DA levels and induced upregulation of the neural activity in the nucleus accumbens (NAc) as evaluated by Fos expression. This optogenetic suppression of DA neuron firing immediately evoked aversive responses to the previously preferred dark room and led to aversive learning toward the optogenetically conditioned place. Importantly, this place aversion was abolished by knockdown of dopamine D2 receptors but not by that of D1 receptors in the NAc. Silencing of DA neurons in the VTA was thus indispensable for inducing aversive responses and learning through dopamine D2 receptors in the NAc.
UR - http://www.scopus.com/inward/record.url?scp=84899656616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84899656616&partnerID=8YFLogxK
U2 - 10.1073/pnas.1404323111
DO - 10.1073/pnas.1404323111
M3 - Article
C2 - 24737889
AN - SCOPUS:84899656616
SN - 0027-8424
VL - 111
SP - 6455
EP - 6460
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -