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Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

Kim H, Kim TK, Kim JE, Park JY, Lee Y, Kang M, Kim KS, Han PL - Mol Brain (2014)

Bottom Line: However, underlying mechanisms are not clearly understood.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. hhm281920@gmail.com.

ABSTRACT

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.

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Related in: MedlinePlus

AC5 KO mice produced behavioral preferences for KO pellets based on an olfactory cue-directed option. (A, B) Western blots showing the siRNA-mediated down-regulation of the Gαolf levels in the olfactory epithelium in WT mice and their quantification (A). Blocking of the preferred choices for KO food pellets in AC5 KO mice after the infusion of Gαolf-siRNA into the olfactory epithelium (B, C) Behavioral choices of AC5 KO mice for KO pellets vs. WT pellets whose surfaces were peeled off. (D) Behavioral choices of AC5 KO mice for fresh pellet pasted with KO-food eluate vs. fresh-food eluate at gradually diluted concentrations and for fresh pellet pasted with WT-food eluate vs. fresh-food eluate. (E, F) Behavioral choices of AC5 KO mice for WT pellets vs. KO pellets that were heated (E) or autoclaved (F). (G-J) Behavioral choices of AC5 KO mice for food pellets that were pasted with WT urine vs. KO urine (G), for food pellets that were mingled with WT bed vs. KO bed (H), for food pellets that were pasted with WT serum vs. KO serum (I), and for food pellets that were pasted with WT saliva vs. KO saliva (J). Data were mean ± SEM (n = 7-12). * and ** denote the difference between indicated groups at p <0.05 and p <0.01, respectively. One-way ANOVA, Tukey's HSD post hoc test (A), Two-way repeated measures ANOVA, Holm-Sidak post hoc test (B), Two-way ANOVA and Tukey's HSD post hoc test (C, D), and Student t-test (D, E-J) were used.
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Fig2: AC5 KO mice produced behavioral preferences for KO pellets based on an olfactory cue-directed option. (A, B) Western blots showing the siRNA-mediated down-regulation of the Gαolf levels in the olfactory epithelium in WT mice and their quantification (A). Blocking of the preferred choices for KO food pellets in AC5 KO mice after the infusion of Gαolf-siRNA into the olfactory epithelium (B, C) Behavioral choices of AC5 KO mice for KO pellets vs. WT pellets whose surfaces were peeled off. (D) Behavioral choices of AC5 KO mice for fresh pellet pasted with KO-food eluate vs. fresh-food eluate at gradually diluted concentrations and for fresh pellet pasted with WT-food eluate vs. fresh-food eluate. (E, F) Behavioral choices of AC5 KO mice for WT pellets vs. KO pellets that were heated (E) or autoclaved (F). (G-J) Behavioral choices of AC5 KO mice for food pellets that were pasted with WT urine vs. KO urine (G), for food pellets that were mingled with WT bed vs. KO bed (H), for food pellets that were pasted with WT serum vs. KO serum (I), and for food pellets that were pasted with WT saliva vs. KO saliva (J). Data were mean ± SEM (n = 7-12). * and ** denote the difference between indicated groups at p <0.05 and p <0.01, respectively. One-way ANOVA, Tukey's HSD post hoc test (A), Two-way repeated measures ANOVA, Holm-Sidak post hoc test (B), Two-way ANOVA and Tukey's HSD post hoc test (C, D), and Student t-test (D, E-J) were used.

Mentions: We examined whether or not behavioral preferences for KO pellets in AC5 KO mice relied upon the olfactory sensory system. The infusion of siRNA-Gαolf (the guanine nucleotide-binding protein subunit αolf, a key player in the initial olfaction step) into the olfactory epithelium of AC5 KO mice suppressed preferred choices for KO pellets over WT pellets, indicating that AC5 KO mice exhibited behavioral choice for KO pellets based on an olfactory cue (Figure 2A and B).Figure 2


Adenylyl cyclase-5 in the dorsal striatum function as a molecular switch for the generation of behavioral preferences for cue-directed food choices.

Kim H, Kim TK, Kim JE, Park JY, Lee Y, Kang M, Kim KS, Han PL - Mol Brain (2014)

AC5 KO mice produced behavioral preferences for KO pellets based on an olfactory cue-directed option. (A, B) Western blots showing the siRNA-mediated down-regulation of the Gαolf levels in the olfactory epithelium in WT mice and their quantification (A). Blocking of the preferred choices for KO food pellets in AC5 KO mice after the infusion of Gαolf-siRNA into the olfactory epithelium (B, C) Behavioral choices of AC5 KO mice for KO pellets vs. WT pellets whose surfaces were peeled off. (D) Behavioral choices of AC5 KO mice for fresh pellet pasted with KO-food eluate vs. fresh-food eluate at gradually diluted concentrations and for fresh pellet pasted with WT-food eluate vs. fresh-food eluate. (E, F) Behavioral choices of AC5 KO mice for WT pellets vs. KO pellets that were heated (E) or autoclaved (F). (G-J) Behavioral choices of AC5 KO mice for food pellets that were pasted with WT urine vs. KO urine (G), for food pellets that were mingled with WT bed vs. KO bed (H), for food pellets that were pasted with WT serum vs. KO serum (I), and for food pellets that were pasted with WT saliva vs. KO saliva (J). Data were mean ± SEM (n = 7-12). * and ** denote the difference between indicated groups at p <0.05 and p <0.01, respectively. One-way ANOVA, Tukey's HSD post hoc test (A), Two-way repeated measures ANOVA, Holm-Sidak post hoc test (B), Two-way ANOVA and Tukey's HSD post hoc test (C, D), and Student t-test (D, E-J) were used.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4233066&req=5

Fig2: AC5 KO mice produced behavioral preferences for KO pellets based on an olfactory cue-directed option. (A, B) Western blots showing the siRNA-mediated down-regulation of the Gαolf levels in the olfactory epithelium in WT mice and their quantification (A). Blocking of the preferred choices for KO food pellets in AC5 KO mice after the infusion of Gαolf-siRNA into the olfactory epithelium (B, C) Behavioral choices of AC5 KO mice for KO pellets vs. WT pellets whose surfaces were peeled off. (D) Behavioral choices of AC5 KO mice for fresh pellet pasted with KO-food eluate vs. fresh-food eluate at gradually diluted concentrations and for fresh pellet pasted with WT-food eluate vs. fresh-food eluate. (E, F) Behavioral choices of AC5 KO mice for WT pellets vs. KO pellets that were heated (E) or autoclaved (F). (G-J) Behavioral choices of AC5 KO mice for food pellets that were pasted with WT urine vs. KO urine (G), for food pellets that were mingled with WT bed vs. KO bed (H), for food pellets that were pasted with WT serum vs. KO serum (I), and for food pellets that were pasted with WT saliva vs. KO saliva (J). Data were mean ± SEM (n = 7-12). * and ** denote the difference between indicated groups at p <0.05 and p <0.01, respectively. One-way ANOVA, Tukey's HSD post hoc test (A), Two-way repeated measures ANOVA, Holm-Sidak post hoc test (B), Two-way ANOVA and Tukey's HSD post hoc test (C, D), and Student t-test (D, E-J) were used.
Mentions: We examined whether or not behavioral preferences for KO pellets in AC5 KO mice relied upon the olfactory sensory system. The infusion of siRNA-Gαolf (the guanine nucleotide-binding protein subunit αolf, a key player in the initial olfaction step) into the olfactory epithelium of AC5 KO mice suppressed preferred choices for KO pellets over WT pellets, indicating that AC5 KO mice exhibited behavioral choice for KO pellets based on an olfactory cue (Figure 2A and B).Figure 2

Bottom Line: However, underlying mechanisms are not clearly understood.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemoon-Gu, Seoul, 120-750, Republic of Korea. hhm281920@gmail.com.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus