Figure 4. Kirrel3 regulates the activity of CA3 neurons during development.

(A) Evoked responses at −70 and 0 mV of a CA3 neuron after stimulation of the MF pathway in Kirrel3 WT and KO mice. Lower traces show responses of the same cells after perfusion of 0.5 μm DCG-IV. (B) Average excitatory/inhibitory (E/I) ratio for CA3 neurons recorded from P14–P16 WT and KO mice. n = 15 cells from five WT animals and 24 cells from five KO animals. p = 0.02 with unpaired t-test. (C) Examples of anti-cFos staining in CA3 neurons from P14 mice. Note increased cell staining in Kirrel3 KO mice after 25 min stimulation (stim) in a novel, enriched environment. (D) Quantification of cFos-positive CA3 neurons at P14. n = 14 (WT no stim), 15 (WT stim), 15 (KO no stim), and 15 (KO stim) sections from three mice per condition. Two-way ANOVA indicates there is a significant difference among condition (no stim vs stim) and genotype. p values from post-tests are 0.0001 (KO no stim vs KO stim) and 0.0004 (WT stim vs KO stim). (E–H) Quantification of MF synapse structure in adult mice. n = 115 WT and 131 KO synapses from three mice per genotype. Two-tailed t-tests indicate p = 0.01 (E), p < 0.0001 (G), and p = 0.002 (H). (I, J) Tracings of representative DiI-labeled MF synapses from adult (P60–P75) Kirrel3 WT and KO mice. (K) Quantification of cFos-positive cells in area CA3 of adult mice. n = 14 (WT no stim), 14 (WT stim), 16 (KO no stim), and 16 (KO stim) sections from three different mice per condition. Two-way ANOVA indicates there is a significant difference among condition (no stim vs stim) but not genotype. p values from post-tests are 0.0005 (WT no stim vs WT stim) and 0.003 (KO no stim vs KO stim). All graphs show mean ± SEM.

DOI: http://dx.doi.org/10.7554/eLife.09395.011

Figure 4—figure supplement 1. Spontaneous mEPSC activity of CA3 and DG neurons is normal in the absence of Kirrel3.

(A, B) Graphs depicting time spent in motion (gray) and stationary (orange) of P14 (A) and adult P60–P75 (B) Kirrel3 WT and KO mice during cFos environmental stimulation. No significant differences by two-tailed t-test. Mean ± SEM is shown. n = 3 mice of each age and genotype. (C, D) Miniature excitatory postsynaptic current (mEPSC) amplitudes and frequencies from P17–P21 CA3 neurons. n = 12 cells from two WT animals and 14 cells from five KO animals. No significant differences by unpaired t-tests. (E, F) mEPSC amplitudes and frequencies from P17–P21 DG neurons. n = 16 cells from three WT animals and 21 cells from three KO animals. No significant differences by unpaired t-tests. All bar graphs show mean ± SEM.

DOI: http://dx.doi.org/10.7554/eLife.09395.012