Generation of Animal Model.

<p>The presence of sperm was used to indicate gestation day 1 (GD 1). Rat dams or pups were exposed to a liquid diet containing ethanol either during the: (i) 1st trimester equivalent  =  prenatal ethanol exposure 1 (PNEE₁); (ii) 2^nd trimester equivalent  =  prenatal ethanol exposure 2 (PNEE₂); or (iii) 3^rd trimester equivalent  =  ethanol exposure 3 (EE₃). Appropriate pair-fed and ad libitum animals were also reared. Dentate gyrus field recordings were conducted in early adulthood (postnatal day (PD) 50–70).</p

Long term-potentiation induced by high frequency stimulation in hippocampal slices.

<p>(A) Field excitatory postsynaptic potential (fEPSP, slope) recorded before and after HFS in slices from all treatment groups. (B) Effects of developmental ethanol exposure on LTP. No significant main effect of sex was obtained, thus data from male and female offspring were pooled together. Each point and bar graph shown is the mean ± SEM. Insert illustrates samples of traces obtained from corresponding groups; fEPSP recorded before (gray) or 1 hour (black) after conditioning stimulation are superimposed. Scale bar represents 0.5 mV by 10 ms. a, significantly different from AL. AL, ad libitum; PNEE₁, prenatal ethanol exposure 1; PNEE₂, prenatal ethanol exposure 2; EE₃, ethanol exposure 3; PF₁, pair-fed 1; PF₂, pair-fed 2; SI₃, sham intubated 3.</p

Maternal Parameters.

<p>The values represent mean ± SEM. AL, ad libitum; BEC, blood ethanol concentration; EE, ethanol exposed; na, not applicable; PF, pair-fed; PNEE, prenatal ethanol exposed.</p>*<p>BEC values taken from pups on postnatal day 4.</p

Offspring Developmental Data.

<p>The values represent mean weight (g) ± SEM. AL, ad libitum; BEC, blood ethanol concentration; EE, ethanol exposed; PD, postnatal day; PF, pair-fed; PNEE, prenatal ethanol exposed; SI, sham intubated.</p>a<p>Males weighed more than females; <i>p</i><0.01.</p>b<p>Prenatal treatment groups (PF₁, PNEE1, PF₂, and PNEE₂) weighed less than both AL and postnatal treatment (SI₃ and EE₃) groups; <i>p</i><0.05.</p>c<p>EE₃weighed less than both AL and SI₃ groups; <i>p</i><0.05.</p>d<p>Weighed less than AL group; <i>p</i><0.05.</p>e<p>Weighed less than PF₁ group; <i>p</i><0.01.</p

Input/Output Curves and Paired Pulse Ratios.

<p>(A) Paired pulse (PP) ratios with a 50 ms inter-stimulus-interval. (B) Input/output (I/O) curves showing fEPSP slope plotted against stimulus strength for all developmental treatment groups. Baseline synaptic strength increased with increased stimulation in all slices. AL, ad labium; PNEE₁, prenatal ethanol exposure 1; PNEE₂, prenatal ethanol exposure 2; EE₃, ethanol exposure 3; PF₁, pair-fed 1; PF₂, pair-fed 2; SI₃, sham intubated 3.</p

Long term-potentiation induced by theta burst stimulation in hippocampal slices.

<p>(A) Field excitatory postsynaptic potential (fEPSP, slope) recorded before and after TBS in slices from all treatment groups. (B) Effects of developmental ethanol exposure on LTP. No significant main effect of sex was obtained, thus data from male and female offspring were pooled together. Each point and bar graph shown is the mean ± SEM. Insert illustrates samples of traces obtained from corresponding groups; fEPSP recorded before (gray) or 1 hour (black) after conditioning stimulation are superimposed. Scale bar represents 0.5 mV by 10 ms. a, significantly different from AL; b, significantly different from EE_3. AL, ad libitum; PNEE₁, prenatal ethanol exposure 1; PNEE₂, prenatal ethanol exposure 2; EE₃, ethanol exposure 3; PF₁, pair-fed 1; PF₂, pair-fed 2; SI₃, sham intubated 3.</p

Stress most severely affected neurogenesis in the ventral dentate gyrus.

<p>Compared with controls, rats in the CUS group showed decreased proliferation (A), survival (B) and neuronal differentiation (C) in the dentate gyrus. This effect was most pronounced in the ventral, compared to the dorsal, sub-region († indicates significant difference between subregions). * significantly different from control.</p

A stressful spatial navigation task differentially affected protein expression in the dorsal and ventral subregions.

<p>Expression of mature BDNF was not significantly changed by RAWM exposure in either the dorsal or ventral dentate gyrus (A). In contrast, proBDNF was significantly increased in the dorsal dentate, and significantly decreased in the ventral (C). PSD-95 was unchanged in the dorsal, but significantly increased in the ventral dentate (C). * significantly different from control.</p

CUS facilitated long-term spatial memory in the RAWM.

<p>Escape latencies did not differ between control and stressed animals during the acquisition trials (1–12), or on the short-term memory trial (30 min) (A). However, stressed animals took significantly less time to locate the hidden platform on the long-term memory trial (24 hrs). A similar pattern was seen for errors made during search (B). * significantly different from control.</p

CUS and learning were both stressful.

<p>Animals that underwent CUS did not gain weight over the 2-week period of stressor exposure, whereas control animals did (A). Exposure to the CUS paradigm raised corticosterone levels, as did learning in the RAWM (B). Note, however, that learning did not further elevate corticosterone in stressed animals. *significantly different from baseline, † significantly different from Post CUS control.</p