Psychopharmacology (2011) 214:249–260 Table 2 Effects of MD on granule cell morphology CON (n =7) MD (n=7) Dendritic length (μm) Number of branch points Spine density (number of spines/μm) Number of primary dendrites 1,560±130 8.6 ±0.6 0.63±0.04 2.3 ±0.2 1,592±121 7.0±0.6 0.59±0.06 3.1±0.2* MD treatment resulted in an increased average number of primary dendrites per cell (n=7 animals per group, values based on five to seven granule cells per animal) *p<0.05 Experiment IV. Maternal deprivation does not alter synaptic plasticity To examine whether morphological changes in the dentate gyrus affected hippocampal synaptic function, we examined LTP in the dentate gyrus using TBS. TBS in the absence of bicuculline did neither in CON nor in MD animals result in synaptic potentiation (data not shown). In addition, the presence of the stress hormone corticosterone prior to and during TBS did not change this (repeated measures ANOVA baseline vs. post-TBS (1–60 min), F1,16 = 0.9; p = 0.36; CON and MD animals pooled). This is not unprecedented since GABAergic innervation is known to drive dentate granule cells in vitro away from their firing threshold (Coulter and Carlson 2007; Wisden et al. 1992). Therefore, we applied TBS in the presence of the GABAergic antagonist bicuculline, which resulted in an overall significant induction of LTP (pooled data from CON and MD rats; repeated measures ANOVA F1,28 = 18.3; p < 0.001). In all experiments described below, bicuculline was present. We found no differences between CON and MD animals in the maximum amplitude of the fEPSP (CON −2.49 ± 0.26 mV; MD −2.46 ± 0.23; p = 0.50) nor in the stimulation intensity that yielded the half-maximal amplitude (CON 1.93 ± 0.01; MD 1.91 ± 0.02; p = 0.49) as determined from the input–output curve. The effects of corticosterone on the degree of LTP was determined by perfusion of 100 nM corticosterone during the second half of baseline recordings, co-terminating with the end of TBS. Corticosterone application in itself had no effect on the magnitude of the signal during the second half of baseline recordings, as revealed by a repeated measures ANOVA comparing baseline 1 (t = −20 to −11 min) with baseline 2 (t = −10 to 0 min; baseline × drug × group, F1,28 = 2.3, p = 0.14; drug × group, F1,28 = 2.4, p = 0.14). For LTP, no significant effects were found on the degree of potentiation of group (CON vs. MD; F1,28 = 0.03; p = 0.86) and drug treatment (F1,28 = 0.04; p = 0.84), nor an interaction effect between these two (F1,28 = 0.002; 255 Fig. 2 Effects of MD on synaptic plasticity. a LTP measured under vehicle conditions (CON n=7, MD n=7). There was no effect of maternal deprivation on the degree of LTP in the dentate gyrus after theta burst stimulation (CON vs. MD; F1,28=0.03; p=0.86) when comparing the second half of baseline recordings (t=−10 to 0 min) with post-TBS recordings. b Long-term potentiation after acute corticosterone application. The degree of LTP was not affected by corticosterone application, and there was no difference between CON (n =7) and MD (n=7) animals (F1,28=0.04; p =0.84), interaction group×treatment (F1,28=0.002; p=0.96) p = 0.96), when comparing the second half of baseline recordings (t = −10 to 0 min) with post-TBS recordings (t = 0–60 min; Fig. 2a, b). Experiment V. MD specifically increases cued fear conditioning Spatial acquisition of the Morris water maze was not changed by maternal deprivation (Fig. 3; F1,18 = 2.15; p = 0.16). Furthermore, CON and MD animals showed similar performance in memory retention after 7 days, as measured by the total time spent in the platform quadrant during the probe trial (CON 20.5 ± 12.1 s (n = 10), MD 28.5 ± 16.2 s (n = 10), p = 0.68). Baseline anxiety, determined in the same groups of animals by elevated plus maze exploration, was also not affected by maternal deprivation. There were no significant differences concerning latency to enter (CON 39.0 ± 15.1 s;