Conditional Gdi1 Deletion on Synaptic Function Figure 8. Delayed Gdi1 deletion leads to exaggerated synaptic phenotypes. (A) Scheme of the slice preparation (B) Evoked EPSCs obtained in Gdi1 WT, Gdi1-null and Gdi1flox/Y for different stimulation intensities were recorded. Scale bars: 500 pA and 15 msec. (C) Bar graph presenting the mean EPSC amplitude at maximal stimulation intensity (50 mA*msec, defined as EPSCmax) in the various genotypes. Number of recorded cells is indicated. ***p,0.001. (D–F) Same presentation as in A–C for the examination of Thalamo-LA synapses. (G) Representative postsynaptic responses to high frequency trains of stimulation in 3 months old Gdi1 WT, Gdi1-null and Gdi1flox/Y animals. Scale bars: 50 pA and 500 msec. (H) Calculated RRP size was decreased in Gdi1flox/Y whereas normal in Gdi1-null mice. ***p,0.001 (I) The refilling rate was lowered in both and conditional Gdi1 mutant mice. *p,0.05. doi:10.1371/journal.pone.0029763.g008 test and associative fear-related memory assessed by trace fear conditioning. Moreover, we also observed loss of aggressive behavior, as previously demonstrated for the Gdi1-null mutants [5]. Taken together, these data suggest that postnatal inactivation of Gdi1 specifically in these brain regions is sufficient and recapitulates the cognitive and social deficits previously seen in Gdi1-null mice. We then investigated the modifications in synaptic plasticity at different synaptic connections in the cortico-lateral amygdala (LA) of P30 Gdi1-null mice. Previous studies have reported that cortical projections to the LA contribute to emotional learning such as fear-related memory, providing qualitative information in addition to the highly responsive sub-cortical pathway [9]. Thus, we examined cortico-LA synaptic physiology in the absence of aGDI by evaluating synaptic depression in the cortico-amygdala pathway. Our results show a strong reduction in the overall synaptic weight at these synaptic contacts, associated with alterations of pre- but not post-synaptic parameters, suggesting that there are specific alterations in the refilling rate of release sites. The examination of synaptic physiology at thalamo-LA and cortico-LA synapses in adult Gdi1flox/Y animals provides the opportunity to directly examine the consequences of pre- and post-synaptic absence of aGDI at excitatory synapses. The first important finding was that in contrast to Gdi1-null mutants, the maximal thalamo-LA EPSC was not changed in conditional Gdi1flox/Y mice (Fig. 8). Taken together with the results showing that the number of active cortico-LA synapses is lowered both in conditional and Gdi1-null mice, this suggests that presynaptic but PLoS ONE | www.plosone.org 9 January 2012 | Volume 7 | Issue 1 | e29763