Hypertrophy of dentate gyrus granule cells and a decreased dynamic range of mossy fiber synaptic transmission in Lis1+/−. A, Representative camera lucida drawings of Golgi-impregnated dentate gyrus granule cells from wild type (left) andLis1+/− (right). Wild-type granule cells possess spiny apical dendrites, lack spines on their soma, and have an axon that emerges from the basal pole of the soma. In contrast, heterotopic Lis1+/− granule cells located in the subgranular region have spiny basal dendrites (indicated byarrows) that give rise to the axon. Note that both the somata and basal dendrites are extremely spiny in both cases. Theinset shows digital image of spiny soma and basal dendrites of the left Lis1+/− granule cell. Scale bars for main panels and inset: 15 μm. B, C, The dynamic range of frequency facilitation is reduced inLis1+/− mossy fiber–CA3 synapses. B, Amplitude of mossy fiber fEPSPs evoked at various stimulation frequencies before and after induction of LTP in wild type (left) and Lis1+/−(right). Mossy fiber synapses were stimulated at a frequency of 0.0125 Hz. Arrows indicate changes in the stimulation frequency (0.025, 0.05, 0.1, 0.2, and 0.33 Hz). Marked facilitation was observed at frequencies as low as 0.05 Hz. After induction of LTP (4 × 100 Hz, 1 sec, 0.03 Hz), the stimulus intensity was decreased to avoid possible nonlinearities during frequency facilitation (Salin et al., 1996). Data are normalized to fEPSPs obtained at 0.025 Hz. Right trace shows the identical experiment performed at mossy fiber synapses inLis1+/−; arrows are not shown inright trace for clarity. C, Summary graph from eight representative experiments in both wild type andLis1+/− shows the range of frequency facilitation before and after LTP induction normalized to 0.025 Hz. The dynamic range of frequency facilitation is significantly less inLis1+/− animals before the induction of LTP (p < 0.001, two-tailed Student'st test). After LTP the degree of facilitation is reduced both in wild type and in Lis1+/− at frequencies above 0.05 Hz. After LTP the degree of facilitation was similar in bothLis1+/− and wild type (p = 0.1, two-tailed paired Student's t test).