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

Abstract

Highlights A new line of mice,Val68Met, mimic human BDNF Val66Met polymorphism. New knock-in BDNF Met mice reverse more efficiently than Val in two separate tasks. Supports theory that BDNF Met allele confers greater sensitivity to the environment. Reversal performance can be dissociated from go/no-go and extinction performance. Phenotypes differ between newer and older BDNF Val66Met mouse models.

The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice

“…It is important to note however, that the BDNFVal66Met mouse model [40], in which the endogenous mouse BDNF gene was replaced with a human sequence, also includes a long carboxy-terminal Histidine repeats tag that may affect the interpretation of the data. Indeed, these two mouse models display divergent behavioral phenotypes [41], including heightened baseline anxiety-like behavior in the mouse model from Chen et al [40], which we did not observe.…”

“…Another important difference between the two mouse lines is that we did not observe a baseline anxiety differences in mice carrying the Val68BDNF and Met68BDNF alleles ([14] and data herein), whereas mice generated by Li and colleagues carrying the human Met66BDNF allele, show heighten basal anxiety levels [66]. Furthermore, Vandenberg et al compared the behaviors of Met66BDNF and Met68BDNF mice as well as their wild-type counterparts in a battery of cognitive paradigms and found numerous additional differences [67]. It is important to note that our knockin mouse line and Li and colleagues knockin mouse line are markedly different.…”

Transient food insecurity during the juvenile-adolescent period affects adult weight, cognitive flexibility, and dopamine neurobiology

“…These data are in line with findings in human literature that females are at higher risk to develop obesity with FI experience. [32][33][34] In male mice, feeding history affected reversal learning in adulthood We next used a 4-choice odor-based foraging (4COF) task [35][36][37][38] (Figure 2A) to test how juvenile-adolescent feeding history affected capacity for learning and cognitive flexibility in adulthood. The mice were tested in discrimination and reversal learning phases in which a reward was obtained by digging selectively in one of four pots with different scented shavings.…”

“…The 4-choice odor-based foraging (4COF) task has been described in previously published work. [35][36][37] In the task, all mice (all groups) were first mildly food restricted for two days to get to a target of ~80-90% of their ad libitum fed weight at that age. Mice were then habituated to the testing arena with four ceramic pots containing a piece of cheerio reward (HoneyNut Cheerios, General Mills) for three 10-min sessions in the next day.…”