Crossover Latencies Research Articles

Low-dose curcumin enhances hippocampal neurogenesis and memory retention in young mice.

Adult neurogenesis generates new functional neurons from adult neural stem cells in various regions, including the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of hippocampal dentate gyrus (DG). Available evidence shows hippocampal neurogenesis can be negatively or positively regulated by dietary components. In a previous study, we reported that curcumin (diferuloylmethane; a polyphenolic found in curry spice) stimulates the proliferation of embryonic neural stem cells (NSCs) by activating adaptive cellular stress responses. Here, we investigated whether subchronic administration of curcumin (once daily at 0.4, 2, or 10mg/kg for 14 days) promotes hippocampal neurogenesis and neurocognitive function in young (5-week-old) mice. Oral administration of low-dose curcumin (0.4mg/kg) increased the proliferation and survival of newly generated cells in hippocampus, but surprisingly, high-dose curcumin (10mg/kg) did not effectively upregulate the proliferation or survival of newborn cells. Furthermore, hippocampal BDNF levels and phosphorylated CREB activity were elevated in only low-dose curcumin-treated mice. Passive avoidance testing revealed that low-dose curcumin increased cross-over latency times, indicating enhanced memory retention, and an in vitro study showed that low-concentration curcumin increased the proliferative activity of neural progenitor cells (NPCs) by upregulating NF1X levels. Collectively, our findings suggest that low-dose curcumin has neurogenic effects and that it may prevent age and neurodegenerative disease-related cognitive deficits.

Nucleus accumbens shell small conductance potassium channels underlie adolescent ethanol exposure-induced anxiety

Alcohol use typically begins in adolescence, increasing the likelihood of adult mental disorders such as anxiety. However, the cellular mechanisms underlying the consequences of adolescent alcohol exposure as well as the behavioral consequences remain poorly understood. We examined the effects of adolescent or adult chronic intermittent ethanol (CIE) exposure on intrinsic excitability of striatal medium-sized spiny neurons (MSNs) and anxiety levels. Rats underwent one of the following procedures: (1) light–dark transition (LDT) and open-field (OF) tests to evaluate anxiety levels and general locomotion; (2) whole-cell patch clamp recordings and biocytin labeling to assess excitability of striatal MSNs, as well as morphological properties; and (3) western blot immunostaining to determine small conductance (SK) calcium-activated potassium channel protein levels. Three weeks, but not 2 days, after CIE treatment, adolescent CIE-treated rats showed shorter crossover latency from the light to dark side in the LDT test and higher MSN excitability in the nucleus accumbens shell (NAcS). Furthermore, the amplitude of the medium afterhyperpolarization (mAHP), mediated by SK channels, and SK3 protein levels in the NAcS decreased concomitantly. Finally, increased anxiety levels, increased excitability, and decreased amplitude of mAHP of NAcS MSNs were reversed by SK channel activator 1-EBIO and mimicked by the SK channel blocker apamin. Thus, adolescent ethanol exposure increases adult anxiety-like behavior by downregulating SK channel function and protein expression, which leads to an increase of intrinsic excitability in NAcS MSNs. SK channels in the NAcS may serve as a target to treat adolescent alcohol binge exposure-induced mental disorders, such as anxiety in adulthood.

Deletion of Glucocorticoid Receptors in Forebrain GABAergic Neurons Alters Acute Stress Responding and Passive Avoidance Behavior in Female Mice.

The glucocorticoid receptor (GR) is critically involved in regulation of stress responses [inhibition of the hypothalamic-pituitary-adrenal (HPA) axis], emotional behavior and cognition via interactions with forebrain corticolimbic circuity. Work to date has largely focused on GR actions in forebrain excitatory neurons; however, recent studies suggest a potential role mediated by interneurons. Here, we targeted GR deletion in forebrain GABAergic neurons, including the cortical interneurons, using a Dlx5/6-Cre driver line to test the role of forebrain interneuronal GR in HPA axis regulation and behavior. Our data indicate that GR deletion in GABAergic neurons causes elevated corticosterone stress responsiveness and decreased cross-over latencies in a passive avoidance task in females, but not males. Dlx5/6-Cre driven gene deletion caused loss of GR in interneurons in the prefrontal cortex (PFC) and hippocampus, but also in select diencephalic GABAergic neurons (including the reticular thalamic nucleus and dorsomedial hypothalamus). Our data suggest that GR signaling in interneurons is differentially important in females, which may have implications for GR-directed therapies for stress-related affective disease states.

Sensitive Assessment of Hippocampal Learning Using Temporally Dissociated Passive Avoidance Task.

The temporally dissociated passive avoidance (TDPA) paradigm is a variant of passive avoidance testing, and allows for more sensitive investigation of mild impairments in avoidance learning. Passive avoidance learning measures the latency to enter a "dark" context in which an aversive stimulus (foot shock) has been previously experienced using a light-dark box paradigm. Briefly, the animal is placed into the light side of the box and the time spent to cross into the dark side is measured. After entry into the dark chamber, the animal receives a mild (0.4-1.6 mA) footshock and is removed from the box. After a period of time, typically 24 h (note that this is entirely dependent on whether various levels of memory retention, e.g., short or long, are being measured), the animal is placed back into the box and cross-over latency is measured. Passive avoidance is learned after one trial and results in a robust increase in crossover latency. This behavior requires the association between a normally neutral environment and an aversive stimulus, and is dependent on hippocampal function (Stubley-Weatherly et al., 1996; Impey et al., 1998). TDPA extends this learning across multiple once-daily trials, producing a more graded and malleable latency score, and thus allows a more sensitive evaluation of changes in hippocampal function The task remains dependent on an intact hippocampus (Zhang et al., 2008), and subtle changes in hippocampal gene expression can result in robust alterations in TDPA latency scores (Eagle et al., 2015). We describe here a common method used to assess TDPA learning in mice.

Effects of Synthetic Cannabinoid JWH‐018 and Phytocannabinoid Δ9‐THC on Learning and Memory in Mice

The growing popularity of botanical and synthetic cannabinoids among adolescents has resulted in concerns regarding the effects of cannabinoid abuse on certain cognitive processes in the developing brain. Here, the effects of exposure to the phytocannabinoid Δ9‐tetrahydrocannabinol (Δ9‐THC) or the synthetic cannabinoid JWH‐018 on learning and memory were studied in adult mice using two behavioral assays. In passive avoidance studies, mice were placed into a light compartment of a chamber and exposed to three electrical stimulus pulses upon crossing into a dark compartment. The latency to cross was measured prior to conditioning and during subsequent exposures to the chamber. Operant studies included an active‐versus‐inactive nose‐poke discrimination, a nose‐poke contingency reversal, and an extinction condition. In all phases, the number of sessions required to reach criterion performance was measured. Injections of saline, 30 mg/kg Δ9‐THC or 3 mg/kg JWH‐018 were administered in both assays. In passive avoidance studies, chronic treatment with JWH‐018 prior to conditioning significantly reduced crossover latencies, consistent with a profound deficit in learning. In operant studies, neither acquisition nor extinction were affected, but Δ9‐THC treatment dramatically impaired reversal learning. These results suggest that Δ9‐THC or JWH‐018 use may produce deficits in learning depending upon the frequency and patterns of use, and that these two cannabinoids may impact different cognitive domains. These studies were funded by NIGMS IDeA Program award(GM110702), UAMS Translational Research Institute(RR029884) and by ASPET SURF awards to COC and KDC.

Low Latency Coding: Convolutional Codes vs. LDPC Codes

This paper compares the performance of convolutional codes to that of LDPC block codes with identical decoding latencies. The decoding algorithms considered are the Viterbi algorithm and stack sequential decoding for convolutional codes and iterative message passing for LDPC codes. It is shown that, at very low latencies, convolutional codes with Viterbi decoding offer the best performance, whereas for high LDPC codes dominate - and sequential decoding of convolutional codes offers the best performance over a range of intermediate latency values. The crossover latencies - i.e., the latency values at which the best code/decoding selection changes - are identified for a variety of code rates (1/2, 2/3, 3/4, and 5/6) and target bit/frame error rates. For sequential decoding, both blockwise and continuous resynchronization procedures are used to allow the decoder to recover the correct path. The results indicate that sequential decoding substantially extends (beyond what is possible with Viterbi decoding) the range of latency values over which convolutional codes prove advantageous compared to LDPC block codes.

High dose bisphenol A impairs hippocampal neurogenesis in female mice across generations

Bisphenol A (BPA) is used as a monomer during the manufacture of polycarbonate plastics and epoxy resins. However, BPA adversely affects reproductive organ growth and development, and it has been proposed that the detrimental effects of BPA could extend to future generations. The present study was conducted to evaluate the transgenerational effects of BPA on hippocampal neurogenesis and neurocognitive function. Pregnant female C57BL/6 mice (F0) were exposed to BPA (0.1–10mg/kg) from gestation day 6 to 17, and female offspring (F2) from F1 generation mice were prepared. It was found that exposure of F0 mice to BPA at 10mg/kg decreased the number of newly generated cells in the hippocampi of F2 female mice. Passive avoidance testing revealed that high-doses BPA (1mg/kg and 10mg/kg) decreased cross-over latency time in F2 mice, suggesting a BPA-mediated neurocognitive deficit in terms of memory retention. Furthermore, it was found that levels of phospho-ERK, brain-derived neurotrophic factor (BDNF), and phospho-CREB in hippocampi were significantly lower in F2 mice. Interestingly, the effects of BPA on hippocampal neurogenesis were found to be correlated with altered DNA methylation. In particular, high-dose BPA exposure increased DNA methylation of the CREB regulated transcription coactivator 1 (Crtc1) generated in F2 mice. These findings suggest that BPA exposure of pregnant mothers could adversely affect hippocampal neurogenesis and cognitive function in future generations by modulating the ERK and BDNF–CREB signaling cascades.

The APP-interacting protein FE65 is required for hippocampus-dependent learning and long-term potentiation

FE65 is expressed predominantly in the brain and interacts with the C-terminal domain of beta-amyloid precursor protein (APP). We examined hippocampus-dependent memory and in vivo long-term potentiation (LTP) at the CA1 synapses with isoform-specific FE65 knockout (p97FE65(-/-)) mice. When examined using the Morris water maze, p97FE65(-/-) mice were impaired for the hidden platform task but showed normal performance in the probe test. To further discriminate the role of FE65 in acquisition and memory consolidation, we examined p97FE65(-/-) mice with temporal dissociative passive avoidance (TDPA) and contextual fear conditioning (CFC). p97FE65(-/-) mice showed impaired short-term memory for both TDPA and CFC when tested 10 min after training. After multiple TDPA training sessions, the crossover latency of some p97FE65(-/-) mice reached the cutoff value, but it significantly decayed in 8 d. At the Schaffer collateral-CA1 synapses, p97FE65(-/-) mice showed defective early-phase LTP (E-LTP). These results demonstrate novel roles of FE65 in synaptic plasticity, acquisition, and retention for certain forms of memory formation.

Strain-dependent Differences of Locomotor Activity and Hippocampus-dependent Learning and Memory in Mice.

The behavioral phenotypes of out-bred ICR mice were compared with those of in-bred C57BL/6 and BALB/c mice. In particular, this study examined the locomotor activity and two forms of hippocampus-dependent learning paradigms, passive avoidance and object recognition memory. The basal open-field activity of the ICR strain was greater than that of the C57BL/6 and BALB/c strains. In the passive avoidance task, all the mice showed a significant increase in the cross-over latency when tested 24 hours after training. The strength of memory retention in the ICR mice was relatively weak and measurable, as indicated by the shorter cross-over latency than the C57BL/6 and BALB/c mice. In the object recognition memory test, all strains had a significant preference for the novel object during testing. The index for the preference of a novel object was lower for the ICR and BALB/c mice. Nevertheless, the variance and the standard deviation in these strains were comparable. Overall, these results confirm the strain differences on locomotor activity and hippocampus-dependent learning and memory in mice.

Mnemonic effects of testosterone and its 5α-reduced metabolites in the conditioned fear and inhibitory avoidance tasks

Experiments were conducted to examine whether performance in hippocampally-mediated learning tasks is influenced by testosterone (T) and/or its 5α-reduced metabolites, dihydrotestosterone (DHT) and 3α-androstanediol (3α-diol). Performance in the conditioned fear and inhibitory avoidance tasks were examined in intact and gonadectomized (GDX), androgen-replaced rats. In Experiment 1, the behavior of intact and GDX rats in the conditioned fear paradigm were compared. GDX rats spent more time freezing, an index of increased learning, in the context, hippocampally-mediated task, but not in the cued, amygdala-mediated task. In Experiment 2, GDX rats were administered T, DHT, 3α-diol, estrogen (E 2), or vehicle 1 mg/kg sc after training in the conditioned fear paradigm. T-, 3α-diol-, or E 2-, compared with vehicle-administered rats, spent significantly more time freezing in the contextual, but not the cued, condition. In Experiment 3, intact compared with GDX rats had significantly longer crossover latencies, indicating better performance, in the inhibitory avoidance task. In Experiment 4, T, DHT, 3α-diol, or vehicle 1 mg/kg sc was administered to GDX rats immediately following training in the inhibitory avoidance task. Rats administered T, DHT, or 3α-diol had significantly longer crossover latencies compared with vehicle controls. In Experiment 5, androgen levels in the hippocampus were elevated 1 h following administration, when androgen exposure is essential for consolidation. These data indicate that androgens effects to enhance learning may be mediated in part by actions of 5α-reduced metabolites in the hippocampus.

Estrogen has mnemonic-enhancing effects in the inhibitory avoidance task

Gonadal hormones, such as estrogen, can alter cognitive performance. The present studies investigated the relationship between performance on the inhibitory avoidance task and endogenous fluctuations in ovarian hormones and estrogen replacement. In Experiment 1, proestrous or diestrous I female, or male, rats were trained in the inhibitory avoidance task. Following a 24-h intertrial delay, when female rats were tested in metestrus or diestrus II, no differences in crossover latencies were observed among groups. In Experiment 2, female rats in proestrus or diestrus I, and male rats, were trained in the inhibitory avoidance task and were tested following a 4-h intertrial delay (so that training and testing were accomplished in the same phase of the cycle). In this paradigm, proestrous rats had significantly longer crossover latencies than did either diestrous I or male rats. Posttraining administration of estrogen, but not progesterone, to ovariectomized rats increased crossover latencies compared to vehicle with a 4-h (Experiment 3) or 24-h (Experiment 4) intertrial delay. In Experiment 5, estrogen administration to ovariectomized rats immediately, but not 1, 2, or 3 h posttraining, increased crossover latencies compared to vehicle. Together, these data suggest that estrogen can have positive mnemonic effects in the inhibitory avoidance task.

Enhancing effects of estrogen on inhibitory avoidance performance may be in part independent of intracellular estrogen receptors in the hippocampus

Estradiol (E 2) can have classical actions via intracellular estrogen receptors (ERs) in the dorsal hippocampus, as well as effects independent of ERs (‘non-genomic’ mechanisms). These experiments investigated whether E 2’s cognitive enhancing effects in the inhibitory avoidance task require actions at ERs in the dorsal hippocampus. Ovariectomized (ovx) rats were administered E 2 (s.c. or to the dorsal hippocampus), an E 2 conjugate (E 2:BSA), or vehicle and/or an ER antagonist, tamoxifen (10 mg/kg s.c.) or ICI 182,780 (10 μg intrahippocampally), or vehicle for 2 days prior to training (Day 3) and testing (Day 4) in the inhibitory avoidance task. Exp 1: crossover latencies in the inhibitory avoidance task were significantly increased in ovx rats with s.c. E 2 silastic capsules or s.c. injections of 1000 or 10 μg E 2 compared to vehicle-administered rats. Exp 2: bilateral inserts of E 2 to the dorsal hippocampus significantly increased crossover latencies compared to vehicle. Exp 3: s.c. tamoxifen, the ER antagonist, did not block the increased crossover latencies produced by 10 μg E 2 s.c. (compared to vehicle). Exp 4: s.c. tamoxifen did not block the increased crossover latencies produced by intrahippocampal E 2 (compared to vehicle). Exp 5: ICI 182,780 was unable to attenuate the increased crossover latencies produced by intrahippocampal E 2. Exp 6: E 2:BSA administered to the dorsal hippocampus significantly enhanced performance on the inhibitory avoidance task compared to control implants to the hippocampus. The ability of systemic and intrahippocampal E 2 to similarly enhance inhibitory avoidance performance suggests that actions of E 2 in the dorsal hippocampus are sufficient to enhance cognitive performance. Further, that neither tamoxifen nor ICI 182,780 blocked E 2’s enhancing effects on inhibitory avoidance and that E 2:BSA was able to enhance performance suggest that non-genomic mechanisms may in part mediate E 2’s cognitive enhancing performance in this task.

Testosterone increases analgesia, anxiolysis, and cognitive performance of male rats.

Preliminary evidence suggests that testosterone (T) may have anxiety-reducing and cognitive-enhancing properties in animals and people. Performance in a number of affective and cognitive behavioral tasks was examined in intact, T-depleted, and T-depleted and T-replaced male rats. Rats that were gonadally intact (n = 33), gonadectomized (GDX; n = 30), or GDX with silastic capsules of T implanted (n = 28) were tested through a battery of affective tasks (horizontal crossing, open field, elevated plus-maze, emergence, holeboard, social interaction, tailflick, pawlick, and defensive burying) and in the inhibitory avoidance task for cognitive performance. An additional 6 rats per group had plasma androgen concentrations measured and were determined to be physiological for intact rats, supraphysiological for T-implanted rats, and near the nadir for GDX rats. Testosterone implants produced analgesia as shown by the increased tailflick latencies of the GDX rats with silastic capsules of T implanted, relative to intact or GDX rats. Testosterone also produced anxiolysis. Intact rats spent more time interacting with a conspecific and less time burying an electrified prod than did the GDX or T-implanted rats. Intact rats or GDX rats with T implants also spent more time on the open arms of the elevated plus-maze than did GDX rats. Testosterone also enhanced cognitive performance in the inhibitory avoidance task. Intact rats had longer crossover latencies in the inhibitory avoidance task relative to GDX rats; GDX rats with T implants had longer crossover latencies relative to GDX or intact rats. Together, these data demonstrate that endogenous T or administration of T produced analgesia and enhanced affect and cognitive performance of adult male rats.

Progestins influence performance on cognitive tasks independent of changes in affective behavior

In this study, the effects of progestins on various cognitive and affective tasks were investigated. Ovariectomized rats (N = 72) received subcutaneously 0.0, 4.0, or 8.0 mg/kg of progesterone (P), dihydroprogesterone (DHP), or 5α-pregnan-3α-ol-20-one (3α,5α-THP) suspended in 10% ethanol/sesame oil v/v. For the cognitive tasks (Y-maze, inhibitory avoidance, and object recognition), the subjects were injected after habituation and training trials and were tested 24 h later. For the nociception and affective tasks (open field, elevated plus-maze, and tailflick), the subjects were injected 1 or 24 h before testing. P reduced latencies to the goal arm in the Y-maze, enhanced latencies to the shock-associated side of the inhibitory avoidance chamber, and increased the percentage of time with a novel object. DHP reduced latencies to the goal arm, increased the percentage of correct choices in the Y-maze, and increased crossover latencies in the inhibitory avoidance task. 3α,5α-THP administration enhanced performance in the inhibitory avoidance task. P, DHP, and 3α,5α-THP increased the number of entries into the central squares of a brightly lit open field, open arm time in the elevated plus-maze, and tailflick latencies, when administered 1 h, but not 24 h, prior to testing. These data suggest that some progestins, when administered following habituation and training and 24 h prior to testing, produce changes in cognitive performance that do not coincide with overt changes in the affective behaviors examined.

Neurochemical and behavioral recovery after colchicine lesions of the nucleus basalis magnocellularis in rats

Experimentally-induced lesions of the basal forebrain have been used to test the hypothesis that the cholinergic system plays a critical role in learning and memory. In the present study, a basal forebrain infusion of colchicine, a microtubule assembly inhibitor, was used to characterize the relationship between a cholinergic marker and behavioral function. Bilateral infusions were made in the nucleus basalis magnocellularis (NBM) of male Long-Evans rats. At 4 weeks post-lesion, behavioral assessments were made on half of the rats in each group. These rats were sacrificed 1 week later and regional choline acetyltransferase (ChAT) activity was measured. The remaining rats were behaviorally tested 11 weeks post-lesion and sacrificed 12 weeks post-lesion. The brains of additional rats were studied for Nissl-staining, ChAT-, GAD- and metEnk immunoreactivity (IR) and AChE histochemistry. At 5 weeks after colchicine infusion, there was a significant decrease in parietal and frontal cortical ChAT activity, impaired acquisition of a water maze spatial navigation task and decreased passive avoidance cross-over latency. At 12 weeks after colchicine infusion, ChAT activity was decreased in frontal but not parietal cortex; acquisition of the water maze task was not significantly different from vehicle-infused rats, and a significant deficit was observed in passive avoidance latency. ChAT-IR in the NBM showed a significant decrease at both time points, while changes in AChE-stained cortical fibers paralleled the ChAT activity. GAD- and metEnk-IR were decreased but were not different between the two time points. These data show task-specific behavioral recovery associated in time with recovery of regional cholinergic markers.

Effects of intra-ischemic blood pressure on outcome from 2-vessel occlusion forebrain ischemia in the rat

Halothane anesthetized Sprague-Dawley rats underwent 10 min of bilateral carotid artery occlusion with mean arterial pressure (MAP) held at 30, 50 or 60 mmHg. Sham rats did not undergo ischemia. A 7-day recovery interval was allowed. Intra-ischemic electroencephalographic (EEG) changes, behavioral function (Days 5–7), and histologic injury (Day 7) were evaluated. Under similar conditions, cerebral blood flow was determined after 10 min ischemia by the [ 3H]nicotine indicator fractionation technique. EEG isoelectricity was observed in 11 of 11.5 of 10, and 2 of 11 rats in the 30 mmHg, 50 mmHg, and 60 mmHg groups respectively. Neither passive avoidance cross-over latencies nor general motor scores were affected by intra-ischemic MAP and no differences from sham performance were observed. The per cent of CA1 neurons counted as dead (left and right hemispheres combined) was significantly affected by intra-ischemic MAP (72, 46 and 28% in the 30 mmHg, 50 mmHg, and 60 mmHg groups, respectively; P < 0.001. A greater than 50% CA1 neuronal mortality rate was present only in those rats exhibiting EEG isoelectricity. However, the number of rats demonstrating greater than a 25% interhemispheric difference in CA1 neuronal loss was greatest in the 50 mmHg group ( P < 0.02). Hippocampal blood flow decreased in association with severity of hypotension 8±1.35±8, and 48 + ml/100g/min (mean ∓ S.E.M. for 30, 50, and 60 mmHg, respectively; P <0.01. Again, however, the greatest variability in blood flow was observed at MAP = 50 mmHg. These results indicate that reduction of MAP to 30 mmHg during bilateral carotid artery occlusion will yield the most consistent hemodynamic and electrophysiologic events corresponding to reduced inter- and intra-animal variability in histologic outcome in this model of near-complete forebrain ischemia.

Strain differences in sympathetic–adrenal medullary responsiveness and behavior

Three experiments confirmed and extended previous findings from this laboratory regarding strain differences in physiological and behavioral responses of rats to stressful stimulation. In the first experiment, adult male Wistar-Kyoto (WKY) rats had greater plasma levels of norepinephrine and epinephrine and higher mean arterial pressures following 5 min of intermittent footshock (2.0 mA, 0.5-sec duration, every 6 sec) compared to adult male Brown-Norway (B-N) rats. In contrast, basal plasma levels of both catecholamines and resting values of mean arterial pressure and heart rate did not differ between strains when rats were undisturbed in their home cages. The second experiment involved a behavioral comparison of adult male and female WKY and B-N rats during 3 consecutive daily tests in an open field arena. B-N males and females were dramatically more active and reared more frequently during each open field test compared to WKY rats. For the third experiment, adult male and female rats of the two strains were trained in a one-trial passive avoidance task and median crossover latencies were similar for all strain-sex comparisons. However, median 24-hr retention latencies were much greater for WKY male and female rats. These findings indicate that strain differences in the physiological and behavioral responses of WKY and B-N rats are consistent across sexes. Moreover, our studies with these inbred strains of rats provide a convenient model for examining the relationship between sympathetic-adrenal medullary activity and behavioral responses to stressful stimulation.

Retained elements of early avoidance training and relearning of forgotten operants.

In a series of 7 experiments we investigated the possibility that juvenile rats show long-term retention for aspects of early avoidance training and that these retained elements serve to reinforce relearning of the forgotten operants. Rats trained in active or passive avoidance at 23-25 days of age demonstrated the typical juvenile forgetting effect relative to adults after a 28-day interval. However, both juveniles and adults demonstrated marked reductions in locomotor activity prior to retraining which were specific to the apparatus and not dependent on the opportunity to perform an operant during initial training. Juvenile animals given a reminder exposure plus footshock 27 days after training, then single daily nonshock trials (Days 28-30), showed decreasing crossover latencies across days if trained in active avoidance and increasing latencies if trained in passive avoidance. This reappearance of task-appropriate crossover latencies was evident in previously trained juveniles only. Finally, young animals' demonstrated change in crossover latency is associated with subsequent superior acquisition performance, and this change depends upon the presentation of the test trials for its appearance. We suggest that the amelioration of "infantile amnesia asociated with the present procedures is a learning process motivated by Pavlovian components of training which are retained well, by juveniles and adults alike, over intervals typical of ontogeny of memory research.