Study specific and combined estimates from the causal mediation analysis.

<p>The effect of neurogenesis was smaller than the effect of other mechanisms in all studies. The overall effect of neurogenesis was small, non-significant (p = 0.128), and unlikely to account for a large proportion of the observed behavioural effects (upper 95% CI  = 0.34). PMID  =  PubMed ID; DA  =  Dark agouti; SD  =  Sprague-Dawley; MWM  =  Morris water maze; OF  =  open field; FST  =  forced swim test; B/W  =  black/white discrimination task. Error bars are 95% credible intervals.</p

Association between neurogenesis and forgetting.

<p>(A) Raw data extracted from Figure 4F in Akers et al. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113855#pone.0113855-Akers1" target="_blank">[30]</a> and estimated regression lines. While in the predicted direction (negative association), the relationship is not significant within groups (p = 0.12). (B) The causal mediation analysis divides the total effect of the TK transgene into the part that can be attributed to neurogenesis and to all other mechanisms. The effect of neurogenesis accounted for less than half (40%) of the total effect, although there is a great deal of uncertainty in this estimate. Error bars are 95% (thin) and 50% (thick) credible intervals.</p

DSWS testing procedure.

<p>The DSWS test consisted of a training and a test phase separated by a delay that was either 30 seconds or 15 minutes long.</p

Measures assessed during the habituation phase.

<p>We recorded the average number of fruitloops retrieved, arms visited and faecal boli dropped of cNLH and cLH rats during the habituation phase of the delayed spatial win-shift test. Data are presented as means ± standard error of the means.</p

Memory score.

<p>The memory score was based on correct and incorrect arm entries during the test phase only. Data are presented separately for the four experimental groups as means ± standard error of the mean.</p

Sigmoidal curves.

<p>The examples of sigmoidal curves are based on the rats’ individual memory performance. Different types of learning curves were observed, ranging from gradual (<b>A, B</b>) to steep learning curves (<b>C, D</b>). Two exceptional cases were observed with one rat falling off in memory performance between trial 14 and trial 15 (<b>E</b>), and another one leveling off at a negative plateau value of −0.34 (<b>F</b>).</p

<i>CACNA1C</i> gene regulates behavioral strategies in operant rule learning

<div><p>Behavioral experiments are usually designed to tap into a specific cognitive function, but animals may solve a given task through a variety of different and individual behavioral strategies, some of them not foreseen by the experimenter. Animal learning may therefore be seen more as the process of selecting among, and adapting, potential behavioral policies, rather than mere strengthening of associative links. Calcium influx through high-voltage-gated Ca²⁺ channels is central to synaptic plasticity, and altered expression of Ca_v1.2 channels and the <i>CACNA1C</i> gene have been associated with severe learning deficits and psychiatric disorders. Given this, we were interested in how specifically a selective functional ablation of the <i>Cacna1c</i> gene would modulate the learning process. Using a detailed, individual-level analysis of learning on an operant cue discrimination task in terms of behavioral strategies, combined with Bayesian selection among computational models estimated from the empirical data, we show that a <i>Cacna1c</i> knockout does not impair learning in general but has a much more specific effect: the majority of <i>Cacna1c</i> knockout mice still managed to increase reward feedback across trials but did so by adapting an outcome-based strategy, while the majority of matched controls adopted the experimentally intended cue-association rule. Our results thus point to a quite specific role of a single gene in learning and highlight that much more mechanistic insight could be gained by examining response patterns in terms of a larger repertoire of potential behavioral strategies. The results may also have clinical implications for treating psychiatric disorders.</p></div

Overall memory score.

<p>The overall memory score was calculated on the basis of both the training and the test phase. Data are presented separately for the four experimental groups as means ± standard error of the mean, **p<0.01.</p

Total test time.

<p>The total time needed to complete a trial included both the training and the test phase. Data are averaged across three consecutive trials and presented separately for the four experimental groups as means ± standard error of the mean.</p

Learning measures.

<p>(<b>A</b>) The amplitude and (<b>B</b>) learning maximum were calculated on the basis of individual learning curves. Data are presented separately for the four experimental groups as means ± standard error of the mean, *p<0.05.</p