Fig. 2
From: CLN3 disease disrupts very early postnatal hippocampal maturation
CLN3 disease hippocampus is significantly hypoexcitable in response to perforant path (PP) stimulation by p7. (A) The PP was stimulated, and the response was measured using voltage sensitive dye imaging in hippocampal slices from (B) p7, (C) p14, and (D) p21 Cln3−/− and Cln3+/+ mice. Raster plots of average fluorescence change (DF/F, warm colors excitation, cool colors inhibition) over time (x axis) and location within hippocampus (y axis) are shown. Stimulation of Cln3+/+ slices results in robust excitation of the dentate gyrus (DG) that spreads to the CA proper (hilus, CA3, CA1) at p7. In Cln3+/+ slices from older (p14 and p21) animals demonstrates increased gating function of the DG, as the spread of excitation from the DG to the CA proper is reduced. In Cln3−/− animals, the DG is significantly hypoexcitable at p7. DG excitability improves by p14, but by p21 the CA proper region becomes hypoexcitable, consistent with prior studies of older Cln3−/− mice. For each age group, Cln3−/− vs. Cln3+/+ rasters were compared using a permutation sampling method with 1000 iterations. Regions of significant (p < = 0.05) hypoexcitability are shown in purple. N = at least 10 slices from 5 animals per condition.
