Conditional Gdi1 Deletion on Synaptic Function Figure 4. Gdi1flox/Y mice showed impaired working and associative memory and overfriendly behavior. (A–B) Gdi1flox/Y (n = 14) and Gdi1lox/Y (n = 12) mice were tested for 10 days in Radial Maze as described in Materials and Methods. (A) Mean number of errors until eight correct choices were made. (B) Learning performance expressed as the mean number of correct arm choices before the first error. Data points represent the mean 6 SE. Black squares are Gdi1lox/Y animals and white squares are Gdi1flox/Y. (C–D) Gdi1flox/Y (n = 15) and Gdi1lox/Y (n = 15) animals were tested in trace fear conditioning. (C) Average percentage of freezing displayed during each 15 seconds of CS presentation, during the training session. Data points represent mean freezing 6 SE. Black squares are Gdi1lox/Y animals and white squares are Gdi1flox/Y. (D) Average percentages of freezing during the context memory test. (E–F–G) Gdi1flox/Y (n = 10) and Gdi1lox/Y (n = 10) mice were tested in the resident intruder test. (E) Cumulative duration of the offensive attacks. (F) Total number of attacks. (G) Cumulative duration of the time spent sniffing the snout area of the intruder. The histograms represent the mean 6 SE. *p,0.05, **p,0.01, ***p,0.001. doi:10.1371/journal.pone.0029763.g004 10 mA*ms: Gdi1 WT: 328667 pA; Gdi1-null: 110641 pA, p,0.01, n = 8 and 14 cells, respectively, Fig. 6C1). Furthermore, when extrapolated, the I/O curves from both genotypes gave different eEPSCmax values, suggesting that the synaptic weight of cortico-LA synapses was altered in the absence of aGDI (eEPSCmax: Gdi1 WT: 491674 pA; Gdi1-null: 217646 pA, p,0.01). In accordance with previous results, the quantal size (Q) at cortico-LA synapses was unaffected in the absence of aGDI. Indeed, by replacing part of the external Ca2+-concentration with strontium ions (Sr2+), a ‘‘loose’’ synchronization of vesicular fusion is usually obtained, allowing the analysis of currents associated with single fusion events in the tail of the main EPSC (Fig. 6D1). A careful analysis of these desynchronized events showed that mEPSC amplitude at cortico-LA synapses was comparable in both genotypes (Sr2+ mEPSC: Gdi1 WT: 7.3360.8 pA; Gdi1-null: 7.2260.48 pA, p.0.05, n = 4 cells in each condition) and resembled global miniature activity (Fig. 6D2). Thus, alteration of the I/O curve did not seem to result from a change in quantal size. Modification of some pre-synaptic parameters at cortico-LA synapses absent in aGDI Short-term synaptic plasticity is essentially determined by residual calcium in the synaptic terminal and by the rate at which release sites are refilled by fusion-competent synaptic vesicles [14]. PLoS ONE | www.plosone.org 6 January 2012 | Volume 7 | Issue 1 | e29763