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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

Whisker trimming in WT and AC5 KO mice switched on-and-off behavioral preferences for KO food pellets in opposite ways. (A) Photographs showing a mouse with normal whiskers or whiskers cut to the fur level and respective mouse symbols. (B, C) Whisker trimming in WT (B) and AC5 KO mice (C) had no effect on their behavioral preferences for rough pellets over smooth ones. (D) Whisker trimming or whiskers glued to the snout and chin in WT mice induced behavioral preferences for KO pellets over WT pellets. (E) Temporal changes of whisker trimming effects in WT mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak post-hoc test: time [F(3, 42) = 11.22, p <0.001], food [F(1,14) = 423.4, p <0.001], and time × food interaction [F(3,42) = 7.517, p <0.001]. (F) Whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. (G) Temporal changes of whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak test: time [F(3, 36) = 0.7297, p = 0.5410], food [F(1,12) = 25.95, p <0.001], and time x food interaction [F(3,36) = 2.832, p = 0.0519]. Mouse symbols: WT (black) and AC5 KO (red) with or without whiskers. Data are presented as the mean ± SEM (n = 7-20), * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
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Fig4: Whisker trimming in WT and AC5 KO mice switched on-and-off behavioral preferences for KO food pellets in opposite ways. (A) Photographs showing a mouse with normal whiskers or whiskers cut to the fur level and respective mouse symbols. (B, C) Whisker trimming in WT (B) and AC5 KO mice (C) had no effect on their behavioral preferences for rough pellets over smooth ones. (D) Whisker trimming or whiskers glued to the snout and chin in WT mice induced behavioral preferences for KO pellets over WT pellets. (E) Temporal changes of whisker trimming effects in WT mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak post-hoc test: time [F(3, 42) = 11.22, p <0.001], food [F(1,14) = 423.4, p <0.001], and time × food interaction [F(3,42) = 7.517, p <0.001]. (F) Whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. (G) Temporal changes of whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak test: time [F(3, 36) = 0.7297, p = 0.5410], food [F(1,12) = 25.95, p <0.001], and time x food interaction [F(3,36) = 2.832, p = 0.0519]. Mouse symbols: WT (black) and AC5 KO (red) with or without whiskers. Data are presented as the mean ± SEM (n = 7-20), * and ** denote the difference between indicated groups at p <0.05 and p <0.01.

Mentions: A potential role of whiskers in the discrimination of rough food pellets was examined. WT mice with the vibrissa cut to the fur level (Figure 4A) showed similar behavioral preferences as those of WT mice with intact whiskers for rough pellets over smooth ones (Figure 4B). AC5 KO mice with cut whiskers also retained the same behavioral preference for rough pellets over smooth ones (Figure 4C) as AC5 KO mice with intact whiskers (Figure 1I and J).Figure 4


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)

Whisker trimming in WT and AC5 KO mice switched on-and-off behavioral preferences for KO food pellets in opposite ways. (A) Photographs showing a mouse with normal whiskers or whiskers cut to the fur level and respective mouse symbols. (B, C) Whisker trimming in WT (B) and AC5 KO mice (C) had no effect on their behavioral preferences for rough pellets over smooth ones. (D) Whisker trimming or whiskers glued to the snout and chin in WT mice induced behavioral preferences for KO pellets over WT pellets. (E) Temporal changes of whisker trimming effects in WT mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak post-hoc test: time [F(3, 42) = 11.22, p <0.001], food [F(1,14) = 423.4, p <0.001], and time × food interaction [F(3,42) = 7.517, p <0.001]. (F) Whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. (G) Temporal changes of whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak test: time [F(3, 36) = 0.7297, p = 0.5410], food [F(1,12) = 25.95, p <0.001], and time x food interaction [F(3,36) = 2.832, p = 0.0519]. Mouse symbols: WT (black) and AC5 KO (red) with or without whiskers. Data are presented as the mean ± SEM (n = 7-20), * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
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Related In: Results  -  Collection

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Fig4: Whisker trimming in WT and AC5 KO mice switched on-and-off behavioral preferences for KO food pellets in opposite ways. (A) Photographs showing a mouse with normal whiskers or whiskers cut to the fur level and respective mouse symbols. (B, C) Whisker trimming in WT (B) and AC5 KO mice (C) had no effect on their behavioral preferences for rough pellets over smooth ones. (D) Whisker trimming or whiskers glued to the snout and chin in WT mice induced behavioral preferences for KO pellets over WT pellets. (E) Temporal changes of whisker trimming effects in WT mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak post-hoc test: time [F(3, 42) = 11.22, p <0.001], food [F(1,14) = 423.4, p <0.001], and time × food interaction [F(3,42) = 7.517, p <0.001]. (F) Whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. (G) Temporal changes of whisker trimming effects in AC5 KO mice on behavioral preferences for KO pellets over WT pellets. Two-way repeated measures ANOVA, Holm-Sidak test: time [F(3, 36) = 0.7297, p = 0.5410], food [F(1,12) = 25.95, p <0.001], and time x food interaction [F(3,36) = 2.832, p = 0.0519]. Mouse symbols: WT (black) and AC5 KO (red) with or without whiskers. Data are presented as the mean ± SEM (n = 7-20), * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
Mentions: A potential role of whiskers in the discrimination of rough food pellets was examined. WT mice with the vibrissa cut to the fur level (Figure 4A) showed similar behavioral preferences as those of WT mice with intact whiskers for rough pellets over smooth ones (Figure 4B). AC5 KO mice with cut whiskers also retained the same behavioral preference for rough pellets over smooth ones (Figure 4C) as AC5 KO mice with intact whiskers (Figure 1I and J).Figure 4

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