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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 gained preferred behaviors for specific cue-directed options. (A-C) Photographs showing representative sets of food pellets consumed by 5 individuals of WT mice (WT) and AC5 KO mice (KO) for 3 days (A). Initially, five fresh food pellets were presented to each mouse and the mean number (B) and weight (C) of food pellets remaining on the next day were recorded. Two-way repeated measures ANOVA, Holm-Sidak post hoc test: for pellet numbers, genotype [F(1,20) = 17.91, p < 0.001], time [F(3,60) = 138.7, p < 0.001], and genotype × time interaction [F(3,60) = 6.935, p < 0.001]; for pellet weight, genotype [F(1,20) = 29.24, p < 0.001], time [F(3,60) = 43.13, p < 0.001], and genotype × time interaction [F(3,60) = 29.49, p < 0.001]. (D) Photographs showing cork rods chewed by WT and AC5 KO mice. Three cork rods were presented to each mouse in the absence of food pellets and the cork rods remaining on the next day were collected and photographed. (E, F) Photographs showing food-intake for small vs. large food pellets by WT and AC5 KO mice (E) and its quantification (F). Three large (1.5-2.0 cm in diameter) and three small (0.5-1.0 cm in diameter) pellets were presented to each mouse and food pellets remaining on the next day were recorded. (G-J) KO mice preferred KO food pellets to WT pellets (G, H) and rough-pellets to smooth- pellets (I, J). Three WT pellets vs. three KO pellets (G) or three rough vs. three smooth pellets (I) were presented to each mouse and food pellets remaining on the next day were recorded (H, J). Two-way ANOVA and Tukey's HSD test: for both (H, J), no genotype effect, significant food effect, and significant genotype × food interaction. Data are presented as the mean ± SEM (n = 8-11). * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
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Fig1: AC5 KO mice gained preferred behaviors for specific cue-directed options. (A-C) Photographs showing representative sets of food pellets consumed by 5 individuals of WT mice (WT) and AC5 KO mice (KO) for 3 days (A). Initially, five fresh food pellets were presented to each mouse and the mean number (B) and weight (C) of food pellets remaining on the next day were recorded. Two-way repeated measures ANOVA, Holm-Sidak post hoc test: for pellet numbers, genotype [F(1,20) = 17.91, p < 0.001], time [F(3,60) = 138.7, p < 0.001], and genotype × time interaction [F(3,60) = 6.935, p < 0.001]; for pellet weight, genotype [F(1,20) = 29.24, p < 0.001], time [F(3,60) = 43.13, p < 0.001], and genotype × time interaction [F(3,60) = 29.49, p < 0.001]. (D) Photographs showing cork rods chewed by WT and AC5 KO mice. Three cork rods were presented to each mouse in the absence of food pellets and the cork rods remaining on the next day were collected and photographed. (E, F) Photographs showing food-intake for small vs. large food pellets by WT and AC5 KO mice (E) and its quantification (F). Three large (1.5-2.0 cm in diameter) and three small (0.5-1.0 cm in diameter) pellets were presented to each mouse and food pellets remaining on the next day were recorded. (G-J) KO mice preferred KO food pellets to WT pellets (G, H) and rough-pellets to smooth- pellets (I, J). Three WT pellets vs. three KO pellets (G) or three rough vs. three smooth pellets (I) were presented to each mouse and food pellets remaining on the next day were recorded (H, J). Two-way ANOVA and Tukey's HSD test: for both (H, J), no genotype effect, significant food effect, and significant genotype × food interaction. Data are presented as the mean ± SEM (n = 8-11). * and ** denote the difference between indicated groups at p <0.05 and p <0.01.

Mentions: AC5 KO mice exhibited unusual food-intake behaviors, tending to finish one food pellet to the end before starting to eat the next in their home cages, whereas wildtype (WT) mice consumed food pellets near-randomly (Figure 1A-C). When presented with cork rods in a food-pellet size (1.5 cm in diameter × 2.5 cm in length), AC5 KO mice somewhat obsessively nibbled the one that they had been taking, whereas WT mice chewed them indiscriminately (Figure 1D). However, AC5 KO mice did not seek small food pellets over large ones (Figure 1E and F). When simultaneously presented with food pellets that wildtype mice had been taking (WT pellets) and size-matched food pellets that AC5 KO mice had been taking (KO pellets), AC5 KO mice greatly preferred KO pellets over WT pellets (Figure 1G and H). AC5 KO mice showed another preference for food pellets with undulating surfaces (rough pellets) over food pellets with smooth surfaces (smooth pellets) (Figure 1I and J). These results suggest that AC5 KO mice displayed altered food-choice behaviors based on certain sensory cues.Figure 1


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 gained preferred behaviors for specific cue-directed options. (A-C) Photographs showing representative sets of food pellets consumed by 5 individuals of WT mice (WT) and AC5 KO mice (KO) for 3 days (A). Initially, five fresh food pellets were presented to each mouse and the mean number (B) and weight (C) of food pellets remaining on the next day were recorded. Two-way repeated measures ANOVA, Holm-Sidak post hoc test: for pellet numbers, genotype [F(1,20) = 17.91, p < 0.001], time [F(3,60) = 138.7, p < 0.001], and genotype × time interaction [F(3,60) = 6.935, p < 0.001]; for pellet weight, genotype [F(1,20) = 29.24, p < 0.001], time [F(3,60) = 43.13, p < 0.001], and genotype × time interaction [F(3,60) = 29.49, p < 0.001]. (D) Photographs showing cork rods chewed by WT and AC5 KO mice. Three cork rods were presented to each mouse in the absence of food pellets and the cork rods remaining on the next day were collected and photographed. (E, F) Photographs showing food-intake for small vs. large food pellets by WT and AC5 KO mice (E) and its quantification (F). Three large (1.5-2.0 cm in diameter) and three small (0.5-1.0 cm in diameter) pellets were presented to each mouse and food pellets remaining on the next day were recorded. (G-J) KO mice preferred KO food pellets to WT pellets (G, H) and rough-pellets to smooth- pellets (I, J). Three WT pellets vs. three KO pellets (G) or three rough vs. three smooth pellets (I) were presented to each mouse and food pellets remaining on the next day were recorded (H, J). Two-way ANOVA and Tukey's HSD test: for both (H, J), no genotype effect, significant food effect, and significant genotype × food interaction. Data are presented as the mean ± SEM (n = 8-11). * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Fig1: AC5 KO mice gained preferred behaviors for specific cue-directed options. (A-C) Photographs showing representative sets of food pellets consumed by 5 individuals of WT mice (WT) and AC5 KO mice (KO) for 3 days (A). Initially, five fresh food pellets were presented to each mouse and the mean number (B) and weight (C) of food pellets remaining on the next day were recorded. Two-way repeated measures ANOVA, Holm-Sidak post hoc test: for pellet numbers, genotype [F(1,20) = 17.91, p < 0.001], time [F(3,60) = 138.7, p < 0.001], and genotype × time interaction [F(3,60) = 6.935, p < 0.001]; for pellet weight, genotype [F(1,20) = 29.24, p < 0.001], time [F(3,60) = 43.13, p < 0.001], and genotype × time interaction [F(3,60) = 29.49, p < 0.001]. (D) Photographs showing cork rods chewed by WT and AC5 KO mice. Three cork rods were presented to each mouse in the absence of food pellets and the cork rods remaining on the next day were collected and photographed. (E, F) Photographs showing food-intake for small vs. large food pellets by WT and AC5 KO mice (E) and its quantification (F). Three large (1.5-2.0 cm in diameter) and three small (0.5-1.0 cm in diameter) pellets were presented to each mouse and food pellets remaining on the next day were recorded. (G-J) KO mice preferred KO food pellets to WT pellets (G, H) and rough-pellets to smooth- pellets (I, J). Three WT pellets vs. three KO pellets (G) or three rough vs. three smooth pellets (I) were presented to each mouse and food pellets remaining on the next day were recorded (H, J). Two-way ANOVA and Tukey's HSD test: for both (H, J), no genotype effect, significant food effect, and significant genotype × food interaction. Data are presented as the mean ± SEM (n = 8-11). * and ** denote the difference between indicated groups at p <0.05 and p <0.01.
Mentions: AC5 KO mice exhibited unusual food-intake behaviors, tending to finish one food pellet to the end before starting to eat the next in their home cages, whereas wildtype (WT) mice consumed food pellets near-randomly (Figure 1A-C). When presented with cork rods in a food-pellet size (1.5 cm in diameter × 2.5 cm in length), AC5 KO mice somewhat obsessively nibbled the one that they had been taking, whereas WT mice chewed them indiscriminately (Figure 1D). However, AC5 KO mice did not seek small food pellets over large ones (Figure 1E and F). When simultaneously presented with food pellets that wildtype mice had been taking (WT pellets) and size-matched food pellets that AC5 KO mice had been taking (KO pellets), AC5 KO mice greatly preferred KO pellets over WT pellets (Figure 1G and H). AC5 KO mice showed another preference for food pellets with undulating surfaces (rough pellets) over food pellets with smooth surfaces (smooth pellets) (Figure 1I and J). These results suggest that AC5 KO mice displayed altered food-choice behaviors based on certain sensory cues.Figure 1

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