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. 2018 Nov:34:34-41.
doi: 10.1016/j.dcn.2018.05.009. Epub 2018 May 30.

Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies

Angela Vandenberg  1 , Wan Chen Lin  2 , Lung-Hao Tai  2 , Dorit Ron  3 , Linda Wilbrecht  4
Affiliations

Mice engineered to mimic a common Val66Met polymorphism in the BDNF gene show greater sensitivity to reversal in environmental contingencies

Angela Vandenberg et al. Dev Cogn Neurosci. 2018 Nov.
No abstract available

Keywords: Executive function; Flexibility; Learning; Neurotrophin; Updating.

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Figures

Fig. 1
Fig. 1
BDNF Met/Met mice learn a go/no-go task at rates comparable to Val/Val littermates, but show faster acquisition of a reversal. A, Schematic of the go/no-go task. The task had three phases: In phase 1 (shaping) mice learned the task by responding to odorants A (go cue) and B (no-go cue); In phase 2 (training) new odorants C (go cue) and D (no-go cue) were introduced; In phase 3 (reversal), odorants C and D were reversed so that C became the “no-go” cue and D became the “go” cue. B, C, Val/Val (n = 10) and Met/Met (n = 10) mice learned the task at similar rates in go and no-go performance (% correct) during the initial shaping session (A = go cue, B = no-go cue). D, E, They also performed comparably during session 2 when novel odorants C (go) and D (no-go) were introduced. F, G, In phase 3, when go and no-go odors were reversed (DC), Val/Val and Met/Met mice differed in their no-go performance (% no-go correct): A two-way ANOVA (% correct in no-go) showed a significant main effect of genotype and session number (genotype: F(1,84) = 4.03, p = 0.048, session: F(5,84) = 14.05, p < 0.0001) but no significant interaction between the two (F(5,84) = 0.35, p = 0.88). Met/Met mice achieved >80% correct in session 3 while Val/Val mice reached >80% correct in session 4.
Fig. 2
Fig. 2
BDNF Met/Met mice extinguish a go/no-go task at comparable rates. A, Schematic of the extinction training for the ‘go’ cue, which ceased to be rewarded at time 0. A no-go cue was also continuously presented but is not shown in schematic. B, After reaching stable performance above 80% criterion, Met/Met (n = 6) and Val/Val mice (n = 8) showed comparable rates of extinction. Shown as number of completed trials. Genotype F(1,12) = 0.14, p = 0.71, time: F(9,108) = 39, p < 0.0001, interaction: F(9,108) = 0.45, p = 0.91).
Fig. 3
Fig. 3
BDNF Met/Met mice learn a multiple choice discrimination task at rates comparable to Val/Val littermates, but show fewer perseverative errors in acquisition of a reversal. A, Schematic of the task. Scented shavings were introduced in 4 pots. During the initial discrimination training animals learned to discriminate odors in order to find a buried food reward. Pots were shifted after each trial and the discrimination phase ended when the mouse retrieved the reward in 8 out of 10 consecutive trials. During the reversal phase, immediately following discrimination, a previously unrewarded odor predicted the location of the reward and a novel odor was introduced. B, Met/Met (n = 12) and Val/Val (n = 10) mice took similar number of trials to reach criterion in the discrimination phase (p = 0.68), and C, made a similar number of errors (t(20) = 0.13, p = 0.90). D, In the reversal phase, trials to criterion score was comparable between groups (t(20) = 1.1, p = 0.3). E, On the way to reaching criterion, the number of perseverative errors made were fewer in Met/Met compared to Val/Val (t(20) = 3.14, p = 0.005). F, Regressive errors, made after 1 correct, were comparable between genotypes (t(20) = 1.18, p = 0.25).
Fig. 4
Fig. 4
BDNF val66met mice from an alternate line (Chen et al., 2006) commonly studied as an anxiety model, do not show more flexible reversal learning. A, Schematic of the task. B, Met/Met (n = 11) and Val/Val (n = 12) mice took similar number of trials to reach criterion in the discrimination phase (t(21) = 1.14, p = 0.27), and C, made a similar number of errors (t(21) = 1.37, p = 0.19). D, In the reversal phase Trials to criterion (t(21) = 0.22, p = 0.83), perseverative errors (U = 43.50, p = 0.17) and regressive errors (U = 51.50, p = 0.38) did not differ by genotype.
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References

    1. Abidin I., Eysel U.T., Lessmann V., Mittmann T. Impaired GABAergic inhibition in the visual cortex of brain-derived neurotrophic factor heterozygous knockout mice. J. Physiol. (Lond.) 2008;586:1885–1901. - PMC - PubMed
    1. Alfimova M.V., Korovaitseva G.I., Lezheiko T.V., Golimbet V.E. Effect of BDNF Val66Met polymorphism on normal variability of executive functions. Bull. Exp. Biol. Med. 2012;152:606–609. - PubMed
    1. Angelucci F., Brene S., Mathe A.A. BDNF in schizophrenia, depression and corresponding animal models. Mol. Psychiatry. 2005;10:345–352. - PubMed
    1. Bath K.G., Lee F.S. Variant BDNF (Val66Met) impact on brain structure and function. Cogn. Affect Behav. Neurosci. 2006;6(1):79–85. - PubMed
    1. Belsky J., Jonassaint C., Pluess M., Stanton M., Brummett B., Williams R. Vulnerability genes or plasticity genes? Mol. Psychiatry. 2009;14:746–754. - PMC - PubMed

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