Critical period for acoustic preference in mice - PubMed (original) (raw)

. 2012 Oct 16;109 Suppl 2(Suppl 2):17213-20.

doi: 10.1073/pnas.1200705109. Epub 2012 Oct 8.

Affiliations

Critical period for acoustic preference in mice

Eun-Jin Yang et al. Proc Natl Acad Sci U S A. 2012.

Abstract

Preference behaviors are often established during early life, but the underlying neural circuit mechanisms remain unknown. Adapting a unique nesting behavior assay, we confirmed a "critical period" for developing music preference in C57BL/6 mice. Early music exposure between postnatal days 15 and 24 reversed their innate bias for silent shelter, which typically could not be altered in adulthood. Instead, exposing adult mice treated acutely with valproic acid or carrying a targeted deletion of the Nogo receptor (NgR(-/-)) unmasked a strong plasticity of preference consistent with a reopening of the critical period as seen in other systems. Imaging of cFos expression revealed a prominent neuronal activation in response to the exposed music in the prelimbic and infralimbic medial prefrontal cortex only under conditions of open plasticity. Neither behavioral changes nor selective medial prefrontal cortex activation was observed in response to pure tone exposure, indicating a music-specific effect. Open-field center crossings were increased concomitant with shifts in music preference, suggesting a potential anxiolytic effect. Thus, music may offer both a unique window into the emotional state of mice and a potentially efficient assay for molecular "brakes" on critical period plasticity common to sensory and higher order brain areas.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.

Fig. 1.

Measurement of acoustic preference in mice. (A) Open 45-cm by 45-cm arena containing shelters with speakers and nesting material is monitored for 3-h trials. (B) Sample tracking of mice during the first and final 30 min of the acoustic preference tests is shown. For visual clarity, traces were plotted once every 50 samplings (out of 14 samplings per second) and superimposed on the video image of the arena setup. Dark triangular shadows in the corners of the background image depict the shelters with different acoustic stimuli. (B and C) (Left) Typically, mice will actively “explore” the arena in the first 30 min, as indicated by the number of entries into either chamber. (Right) By the final 30 min, most animals indicate their preference (in seconds) by settling into shelters (“dwell”) for extended periods of time.

Fig. 2.

Fig. 2.

Juvenile window for shaping acoustic preference. (A and B) To validate the anxiety measure in our preference test setup, a mouse model of anxiety (28), GAD65−/− mice, were tested and compared with WT (C57BL6/J) mice. GAD65−/− mice (dashed box) show a lower number of center-square crossings (B) during the first 30 min of the preference test (mean ± SEM; *Mann–Whitney U test, P < 0.05), whereas they show a similar distance moved during this time as WT mice (_A_). (_C_) Critical period for music preference in mice. (_D, Upper_) Percentages of naive WT mice, WT mice with exposure to music during P15–P24, or WT mice with exposure to music at >P60 that show a preference for each shelter during the final 30 min of a music vs. silence test. (D, Lower) Cumulative frequency distribution of each experimental group plotted as a function of preference for silence. The majority of naive WT mice choose the silent shelter (black curve, n = 18). This behavior can be modified by exposure to music only during a critical period in the third postnatal week (P15–24: red curve, n = 26; >P60: blue curve, n = 33) (21). The abscissa indicates a preference for the silent chamber, which was calculated by the percentage of time spent in the silent chamber over the total time spent in both chambers (final 30 min). *Kolmogorov–Smirnov test, P < 0.05.

Fig. 3.

Fig. 3.

(A) Reactivation of critical period for music preference. Adult (>P60) WT mice pretreated with VPA for 2 d or NgR−/− mice were passively exposed to music and tested for acoustic preference (as in Fig. 1) before and after exposure. (B) Note the typical preference for silence (dashed and red curves; n = 58, n = 24, and n = 19 for naive WT, NgR−/− baseline, and saline WT mice, respectively) is largely shifted in favor of exposed music in the VPA and NgR−/− groups (blue and purple curves; n = 20 and n = 12 mice, respectively). Conversely, NgR−/− mice housed in silence prefer the silent shelter even more strongly (green curve; n = 11 mice). (C) Specific preference for the previously heard music over previously unheard music in mice with reopened juvenile plasticity. The cumulative frequency distribution of each experimental group is plotted as a function of preference for previously heard music (music 1) in WT and NgR−/− groups. Adult WT mice with VPA treatment paired with music exposure (blue) show a preference for the music 1 compared with saline-treated controls (red; Kolmogorov–Smirnov test, P < 0.05). In comparison to the NgR−/− silence group (green), the NgR−/− group exposed to music 1 (purple) shows a preference for music 1 (NgR−/− music 1 vs. NgR−/− silence; Kolmogorov–Smirnov test, P < 0.03). (D) Preference shift was not observed in WT mice with VPA treatment combined with 7-kHz tone exposure following the same procedure as music exposure in A (n = 19 saline + 7-kHz vs. 27 VPA + 7-kHz tone-exposed WT mice). *P < 0.05, Kolmogorov-Smirnov test.

Fig. 4.

Fig. 4.

Music engages the adult mPFC during reopened plasticity. (A_–_C) Representative response in FOS-EGFP mice of mPFC (Upper and Middle) and primary auditory cortex (Aud. ctx; Bottom) to brief exposure to the music (Upper), 7 kHz (Middle), or silence (C, baseline) previously heard with VPA (A) or saline (B) treatment. (Scale bar, 100 μm.) (D) Quantification of FOS+ cells in the mPFC for WT groups in A_–_C and NgR−/− mice previously exposed either to music or silence as in behavioral experiments. Note the increased neuronal response in the mPFC of VPA-treated, music-exposed WT, and NgR−/− music groups (n = 9 VPA + music vs. 8 saline + music: Mann–Whitney U test, **P < 0.005; VPA vs. n = 5 baseline (zero line): Mann–Whitney U test, §P < 0.03; n = 8 NgR−/− music vs. 7 NgR−/− silence: Mann–Whitney U test, **P < 0.003). In contrast, WT mice exposed to 7-kHz tones did not show an increased FOS response in the mPFC regardless of VPA (A, Middle) or saline (B, Middle) compared with silence (C, Middle; zero line) (n = 6 in each group). (E) Quantification of FOS+ cells in primary auditory cortex of WT mice in A_–_C (Lower). Unlike in the mPFC, VPA treatment did not yield differential FOS responses to music in comparison to saline-treated, music-exposed controls.

Fig. 5.

Fig. 5.

Potential anxiolysis by music exposure reflects juvenile brain plasticity. (A) Increased number of center-square crossings (Fig. 1_A_, dashed box), indicating reduced anxiety (70), during the first 30 min measured in adult WT mice previously exposed to music at P15–P24 (light gray bar, n = 26) suggests anxiolysis in comparison to mice exposed later at >P60 (n = 18) or naive controls (zero line, n = 18). Reduced anxiety was also observed in adult NgR−/− mice (dark gray bar, n = 15) after exposure to music (in comparison to naive NgR−/− mice; zero line, n = 44) and in adult WT mice after VPA paired with music (black bar, n = 20) compared with saline-treated counterparts exposed to music (white bar, n = 19) or naive WT controls (zero line, n = 58). Note that a similar duration of tone exposure (7 kHz) in adult WT mice produced no anxiolytic effect despite VPA treatment (hatched black bar, n = 27) in comparison to saline-treated counterparts also exposed to 7 kHz (hatched white bar, n = 19). *P < 0.05 vs. non–music-exposed controls. (B) Overall distance traveled during the same first 30 min is no different across groups, regardless of exposure to music or 7-kHz tones.

References

    1. Bolhuis JJ. Early learning and the development of filial preferences in the chick. Behav Brain Res. 1999;98:245–252. -PubMed
    1. Gould TJ. Addiction and cognition. Addict Sci Clin Pract. 2010;5:4–14. -PMC -PubMed
    1. Kolb B, et al. Experience and the developing prefrontal cortex. Proc Natl Acad Sci USA. 2012;109(Suppl. 2):17186–17193. -PMC -PubMed
    1. DeCasper AJ, Fifer WP. Of human bonding: Newborns prefer their mothers’ voices. Science. 1980;208:1174–1176. -PubMed
    1. Colombo JA, Bundy RS. A method for the measurement of infant auditory selectivity. Infant Behav Dev. 1981;4:219–223.

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