Figure 5.
Cortical network alterations in mice that overexpress CaV1.2. (A) Representative FOV in grayscale (left) and with pseudocolored ROIs (right). (B) Raw GCaMP6 signal before, during, and after tactile stimulation during a 50-second recording. (C) Network connectivity correlogram. The size of the dot (neuron) represents the sum of that neuron’s weighted CC with all other neurons. The color of the line between 2 dots indicates the unweighted CC between that pair of neurons. Recordings were made from 6 mice in each genotype (CaV1.2Tg− = 95 FOV; CaV1.2Tg+ = 143 FOV). (D) Mice that overexpressed CaV1.2 exhibited significantly more active neurons per mm2 than their WT littermate controls (t236 = 4.67, ∗∗∗∗p = .007; unpaired t test). (E) In addition to the increase in number of active neurons in the CaV1.2Tg+ mice, the number of active connections was greater than those observed in the CaV1.2Tg− mice both during stimulation and the recovery period (effect of genotype F1,708 = 15.06, #p = .0001, ∗∗p = .005, ∗p = .041; Sidak’s). (F) Connection lengths were overall shorter in the CaV1.2Tg+ mice (F1,256 = 14.52, #p = .0002; restricted maximum likelihood), which was most apparent during the baseline period (t256 = 2.65, ∗p = .026; Sidak’s). (G–I) In contrast to the presence of more densely connected neurons, network activity in the CaV1.2Tg+ mice appeared to be less synchronized during the stimulation period. (G) The average percentage of cells that were synchronized with the 3-Hz paw stimulation was ∼70% and was not different between the 2 genotypes. (H) The percentage of time that cells in the FOV were synchronized to the input frequency was modestly reduced in the CaV1.2Tg+ mice compared with their WT littermates (t236 = 2.49, ∗p = .0134; unpaired t test). (I) Similarly, overlapping events between pairs of cells in the CaV1.2Tg+ mice was significantly reduced (t148 = 3.01, ∗∗p = .0023; t test with Welch’s correction). (J) Lastly, network synchronicity during the 3-Hz stimulation (calculated as the number of consecutive events detected divided by 15 and presented as percentage of time) was modestly reduced in the CaV1.2Tg+ mice (t236 = 2.69, ∗∗p = .008; t test). All data are presented as mean ± SEM. CC, correlation coefficient; FOV, field of view; ROI, region of interest; WT, wild-type.
