Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.
BACKGROUND
Behavioral choices in habits and innate behaviors occur automatically in the absence of conscious selection. These behaviors are not easily modified by learning. Similar types of behaviors also occur in various mental illnesses including drug addiction, obsessive-compulsive disorder, schizophrenia, and autism. However, underlying mechanisms are not clearly understood. In the present study, we investigated the molecular mechanisms regulating unconditioned preferred behaviors in food-choices.


RESULTS
Mice lacking adenylyl cyclase-5 (AC5 KO mice), which is preferentially expressed in the dorsal striatum, consumed food pellets nearly one after another in cages. AC5 KO mice showed aversive behaviors to bitter tasting quinine, but they compulsively chose quinine-containing AC5 KO-pellets over fresh pellets. The unusual food-choice behaviors in AC5 KO mice were due to the gain of behavioral preferences for food pellets containing an olfactory cue, which wild-type mice normally ignored. Such food-choice behaviors in AC5 KO mice disappeared when whiskers were trimmed. Conversely, whisker trimming in wildtype mice induced behavioral preferences for AC5 KO food pellets, indicating that preferred food-choices were not learned through prior experience. Both AC5 KO mice and wildtype mice with trimmed whiskers had increased glutamatergic input from the barrel cortex into the dorsal striatum, resulting in an increase in the mGluR1-dependent signaling cascade. The siRNA-mediated inhibition of mGluR1 in the dorsal striatum in AC5 KO mice and wildtype mice with trimmed whiskers abolished preferred choices for AC5 KO food pellets, whereas siRNA-mediated inhibition of mGluR3 glutamate receptors in the dorsal striatum in wildtype mice induced behavioral preferences for AC5 KO food pellets, thus mimicking AC5 KO phenotypes.


CONCLUSIONS
Our results show that the gain and loss of behavioral preferences for a specific cue-directed option were regulated by specific cellular factors in the dorsal striatum, such that the preferred food choices were switched on when either the mGluR3-AC5 pathway was inactive or the mGluR1 pathway was active, whereas the preferred food-choices were switched off when mGluR1 or its downstream pathway was suppressed. These results identify the AC5 and mGluR system in the dorsal striatum as molecular on/off switches to direct decisions on behavioral preferences for cue-oriented options.
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. hhm281920@gmail.com.
Hannah
H
Kim
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. spt21@hanmail.net.
Tae-Kyung
TK
Kim
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. jonin12@nate.com.
Ji-Eun
JE
Kim
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. http39@nate.com.
Jin-Young
JY
Park
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. dbswls8879@nate.com.
Yunjin
Y
Lee
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. max13579@naver.com.
Minkyung
M
Kang
Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea. kskim@kribb.re.kr.
Kyoung-Shim
KS
Kim
Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. plhan@ewha.ac.kr.|Brain Disease Research Institute, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. plhan@ewha.ac.kr.|Department of Chemistry and Nano Science, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. plhan@ewha.ac.kr.
Pyung-Lim
PL
Han
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal; D002755:Choice Behavior; D003463:Cues; D005518:Food Preferences; D018698:Glutamic Acid / Q000378:metabolism; D018345:Mice, Knockout; D008954:Models, Biological; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology*; D011803:Quinine / Q000494:pharmacology; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012903:Smell / Q000187:drug effects; D014110:Touch; D014738:Vibrissae / Q000187:drug effects
D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1; D018698:Glutamic Acid; D011803:Quinine; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V