3.2. Augmented cholinergic gamma oscillations in B6N and 129 mouse strains
Non-selective cholinergic agonist carbachol (concentration range: 5-20 µM) has been widely used to induce gamma oscillations with gamma peak frequencies around ~30-40 Hz (Figure 1a) (Fisahnet al. , 1998; Madencioglu et al. , 2021). In our experiments we perfused slices with 5 µM carbachol for 45-70 min to induce prominent and stable gamma oscillations in an interface recording chamber. After our exclusion criteria, (see section 2.4. Cholinergic gamma oscillations for details ), 57 recordings from CA3 (B6J: N=8 mice, n=24 slices; B6N: N=7 mice, n=14 slices; 129, N=7 mice, n=19 slices) and 44 recordings from CA1 (B6J: N=8 mice, n=18 slices; B6N: N=7 mice, n=13 slices; 129, N=7 mice, n=13 slices) were included in further analysis (Figure 2b).
In the CA3, the slices obtained from B6J substrain generated less prominent gamma oscillations (Figure 2c-e) that was evident by significantly lower integrated (20-80 Hz) gamma power (Figure 2d: F(2,56)=6.201, p=0.004) and gamma peak power (Figure 2e: F(2,56)=6.160, p=0.004) in comparison to both B6N substrain (Integrated Power: p=0.004; Peak Power: p=0.002) and 129 strain (Integrated Power: p=0.006; Peak Power: p=0.016). Interestingly, there was also a significant main effect for gamma peak frequency (Figure 2f: H(2)=10.058, p=0.007) with higher peak frequencies in slices obtained from 129 strain (B6J vs. 129: p<0.05; B6N vs. 129: p<0.05).
In the CA1, although a similar trend (Figure 2g-j) was evident no significant alterations were detected for integrated power (Figure 2h: F(2,43)=3.089, p=0.056). A similar decrease in peak gamma power in B6J strain was evident (Figure 2i: F(2,43)=6.373, p=0.004) in comparison to B6N substrain (p<0.001) which remained only as a trend when compared to 129 strain (Peak Power: p=0.057). Similarly, slices obtained from 129 strain exhibited higher gamma peak frequencies (Figure 2j: H(2)=12.166, p=0.002) compared to other two strains (B6J vs. 129: p<0.05; B6N vs. 129: p<0.05).
Furthermore, we analysed gamma synchrony within and across CA3 and CA1 regions via computing auto- and cross-correlograms (Figure 2k). We detected an increased local gamma correlations in the CA3 (Figure 2l: F(2,56)=3.959, p=0.025) and CA1 (Figure 2m: F(2,56)=5.129, p=0.010) regions of B6N in comparison to B6J (CA3-CA3 correlation: p=0.007; CA1-CA1 correlation: p=0.003). Lastly, similar CA3-CA1 cross-correlations were calculated across three strains (Figure 2n: H(2)=4.225, p=0.121). Collectively, these data demonstrate that hippocampal slices obtained from B6J mouse strain express weaker cholinergic gamma oscillations in comparison to both B6N and 129 mouse strains.