3.3. Reduced associative network activation in the CA3 of 129 mouse strain
Altered CA3 associative collateral network activation might underlie the differences in hippocampal network oscillations across studied mouse strains (Le Duigou et al. , 2014). For this purpose, we used antidromic stimulation of CA3 to generate a synaptically-mediated orthodromic population spike that follows a fast antidromic population spike (Figure. 3a-b; (Behrens et al. , 2005; Fano et al. , 2012). Comparison of IO curves for CA3 antidromic population spikes revealed a statistically significant stimulation strength x strain interaction (Figure 3c: F(8,180)=2.936, p=0.004) with a mild reduction of 129 antidromic responses in higher intensity ranges when compared to B6J substrain (See Figure 3c for posthoc comparisons). Interestingly, we detected a strong strain effect (Figure 3c: F(2,45)=8.224, p<0.001) and stimulation strength x strain interaction (Figure 3d: F(8,180)=3.173, p=0.002) for orthodromic populations spikes. Noteworthy, the orthodromic population spikes of 129 strain were profoundly reduced (See Figure 3d for posthoc comparisons). To assess the CA3 associative collateral network activation independent of antidromic stimulation we calculated normalized orthodromic responses via dividing orthodromic responses to corresponding antidromic responses across stimulation strengths and averaged these values within a slice (one data point per slice; see Figure 3e). Importantly, there was a strong strain effect (Figure 3e: H(2)=9.201, p=0.01) with a profound reduction in the normalized orthodromic responses in 129 strain when compared to B6J (p<0.05). Using the same stimulation configuration, we recorded orthodromic population spikes in the CA1 (Figure 3f). However, we detected no difference between the strains (Figure 3c: F(2,34)=0.183, p=0.833). To sum up, these results demonstrate a differential recruitment of CA3 associative network across three strains with strong reduction in the 129 when compared B6J.