Representative photomicrographs showing KA2 mRNA signal on the right and GluR5 mRNA on the left.

<p>We did not observe changes in expression of either of these transcripts.</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after 21 day treatment with either vehicle, 25 µg/ml or 400 µg/ml corticosterone in drinking water.

<p>*-significantly different from vehicle treated animals (p<0.05, n = 8).</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after CRS.

<p>*-significantly different from unstressed controls (p<0.05, n = 8).</p

ROD of GluR6 mRNA in the dentate gyrus (A) CA3 (B) and CA1 (C) after adrenalectomy and treatment with vehicle (ADX), aldosterone (ADX+Aldo) RU28,362 (ADX+RU362) or corticosterone (ADX+CORT).

<p>(D) A representative autoradiogram of GluR6 mRNA. *-significantly different from sham and ADX+CORT (p<0.05, n = 8).</p

ROD of KA1 mRNA in the dentate gyrus (A) and CA3 (B) after adrenalectomy and treatment with vehicle (ADX), aldosterone (ADX+Aldo) RU28,362 (ADX+RU362) or corticosterone (ADX+CORT).

<p>(C) A representative autoradiogram of KA1 mRNA. *-significantly different from sham and ADX+Cort (p<0.05, n = 8). **-significantly different from ADX (p<0.05, n = 8).</p

Experiments 5 and 6—Stress is necessary for the forced swim to alter consolidated memories.

<p>(A) Experiment 5—Propranolol caused amnesia of inhibitory avoidance memory only if it was administered after the forced swim. Rats were trained in the inhibitory avoidance paradigm on Day 1. On Day 2, they were either forced to swim (Sw) or just handled (NoSw), and immediately afterwards injected with 10 mg/ml/kg Propranolol or saline (NoSw-Sal <i>n</i> = 11, NoSw-Pro <i>n</i> = 10, Sw-Sal <i>n</i> = 10, Sw-Pro <i>n</i> = 11). Rats in the Sw-delPro group (<i>n</i> = 12) were injected with Propranolol 5 h after the swim. The average ± step-through latencies on Day 1 were: NoSw-Sal = 8.5±1.7; NoSw-Pro = 6.5±0.79; Sw-Sal = 7.4±1.5; Sw-Pro = 5.5±0.91; Sw-delPro = 7.9±0.98). The step-through latencies recorded on Day 3 are plotted. The groups did not differ on Day 1, but they differed on Day 3 (F_4,49 = 3.0; <i>p</i> = 0.03). Amnesia, manifested as reduced step-through latencies, was observed only in the Sw-Pro group (all post hoc <i>p</i>s <0.05) (* <i>p</i><0.05). The data indicate the swim activated the consolidated memory. Whether or not inhibitory avoidance was enhanced by the swim could not be determined in this experiment because performance was already maximal after the single conditioning trial. The data cannot be explained by previous work showing that exposure to a novel alerting stimulus can enhance retrieval of conditioned inhibitory avoidance because in that case, beta-endorphin activation triggered beta-noradrenergic and cholinergic processes that acted at the time of retrieval only if the retrieval test was given within less than 6 h <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000570#pbio.1000570-Izquierdo2" target="_blank">[63]</a>,<a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000570#pbio.1000570-Netto1" target="_blank">[64]</a>. (B) Experiment 6—Dexamethasone blocks the swim-induced enhancement of memory. Rats were trained in the intensive left/right discrimination on Day 1. The next day, Dexamethasone (Dex; 0.2 mg/kg i.p.) or saline (Sal) was administered 2 h prior to the forced swim (Sw) or no swim (NoSw) shallow-water control treatments. Retention of the Day 1 left/right discrimination memory was tested on Day 3 by the reversal test. Enhanced memory was observed in the saline-treated animals that were forced to swim (Sal-Sw), but the effect was blocked by the action of Dexamethasone in the (Dex-Sw) group. (* <i>p</i><0.05 compared to the saline-treated no swim (Sal-NoSw) control group).</p

Experiments 8 and 9—Acquisition and retrieval of left-right discrimination does not depend on hippocampus but the swim-induced enhancement of memory does.

<p>(A) Experiment 8a—Bilateral TTX inactivation of dorsal hippocampus in the D1-TTX (black, <i>n</i> = 9) group did not influence left/right discrimination learning in the Y-maze task compared with saline controls (D1-Sal, white, <i>n</i> = 11; <i>p</i>>0.05). (B) Experiment 8b—Another two groups of animals were trained on Day 1 with the intensive training protocol. One hour before the Day 3 reversal test, TTX (D3-TTX, black, <i>n</i> = 7) or saline (D3-Sal, white, <i>n</i> = 11) was infused into both dorsal hippocampi. The TTX injection did not impair retrieval. In fact, there was an opposite tendency for enhanced retrieval in the hippocampus-inactivated group <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000570#pbio.1000570-McDonald1" target="_blank">[65]</a>, but the trend did not reach significance (<i>p</i>>0.05). Thus hippocampus was not necessary for learning or expressing left/right discrimination memory. (C) Experiment 9—Hippocampus was necessary for the swim-induced enhancement of memory. Left/right discrimination was conditioned on Day 1 using the intensive training protocol. On Day 2, rats received bilateral intrahippocampal injections of saline (Sw-Sal, white, <i>n</i> = 11) or TTX (Sw-TTX, black, <i>n</i> = 8), and 1 h later they were forced to swim. Memory was tested by reversal training on Day 3. The numbers of to-criterion errors are reported. The TTX injection attenuated the swim-induced memory enhancement (t₁₇ = 3.47; <i>p</i> = 0.003) (* <i>p</i><0.01). The placement of 20 bilateral injections are depicted on schematic coronal sections <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000570#pbio.1000570-Paxinos1" target="_blank">[66]</a>. The number indicates the section's location posterior to bregma.</p

Experiment 10—The swim-induced inter-hemispheric transfer of lateralized memory required hippocampal function.

<p>Left/right discrimination was conditioned on Day 1 using the intensive training protocol with one hemicortex inactivated by cortical spreading depression (CSD). On Day 2 rats received bilateral hippocampal injections of saline (Lat-Sw-Sal, white, <i>n</i> = 11) or lidocaine (Lat-Sw-Lid, black, <i>n</i> = 21), and then they were forced to swim. Memory was assessed by reversal training 2 h after the swim with the originally trained hemicortex inactivated by CSD. The number of to-criterion errors is reported. The groups did not differ on Day 1 but they differed on Day 2 (t₃₀ = 2.27; <i>p</i> = 0.03). The Day 1 memory was lateralized because rats in the Lat-Sw-Lid group performed as if naïve on Day 2. The swim induced IHT of the lateralized memory because rats in the Lat-Sw-Sal group made more reversal errors on Day 2 (* <i>p</i><0.05).</p

Experimental methods.

<p>A. Timeline. B. Sequential steps in carrying out the within-litter neonatal novelty exposure procedure: (i) Dam is removed from the home cage; (ii) Novel pups are transferred to individual non-home cages and yoked Home pups receive a matching amount of experimenter contact; (iii) After 3 min in the non-home cages, Novel pups are returned to the home cage in which the Home pups remain; (iv) Dam is returned to the home cage. C. Apparatus used to assess rats' ability to compete against a conspecific for exclusive access to chocolate rewards. Note that the runway was sufficiently narrow as to allow only one rat at a time to fully enter.</p

Maternal care during brief 10-min windows immediately after repeated novelty exposure predicts the effect of novelty exposure on CORT habituation among aged offspring.

<p>A. Greater average amount of maternal licking and grooming (LG) was associated with greater day-to-day variability in maternal LG (dots and bars indicate average and range, respectively, of LG across days for individual dams; <i>N</i> = 11 litters). B. Greater average amount of maternal LG was associated with negative novelty scores for CORT habituation (marginally significant). D. Smaller day-to-day variability in maternal LG was significantly correlated with positive novelty scores for CORT habituation.</p