Norepinephrine and posttraining memory consolidation in neonatal rats.

Wistar rat pups, aged Postnatal Day 5, were trained in an olfactory associative learning task with citral odor as the conditioned stimulus (CS) and intraoral infusions of milk as the unconditioned stimulus (US). Following a 30-min training session, pups were injected with either the norephinephrine 13-receptor antagonist propranolol or the β-receptor agonist isoproterenol. Pups were tested 24 hr later for an acquired relative odor preference for the CS. Propranolol injected immediately following training impaired memory for the CS in a dose-dependent manner. This posttraining effect lasted less than 4 hr. Isoproterenol injected immediately after training also impaired memory performance, even at very low doses. These results suggest that posttraining levels of norepinephrine play a critical role in memory consolidation in the newborn, with elevations or decrements in noradrenergic activity resulting in impaired memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Somatic mutation in the neonatal mouse

Several mechanisms that diversify the adult immune repertoire, such as terminal deoxynucleotidyl transferase-dependent N region addition, are not available to the neonatal mouse. One important process that contributes to protective immunity in the adult is somatic mutation, which plays a major role in the generation of high affinity memory B cells. It is not clear whether B cells in the neonatal mouse can activate the somatic mutation machinery. To investigate this, we immunized neonates with poly(L-Tyr,L-Glu)-poly-D,L-Ala-poly-L-Lys complexed with methylated BSA, or (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin. Eight to fourteen days after priming, V(D)J rearrangements of known V(H) genes (V(H)SM7 family) were screened for mutations using a temperature-melt hybridization assay and oligonucleotide probes specific for complementarity-determining regions I and II; possible mutations were confirmed by sequence analysis. More mutations per sequence were found in heavy chains from neonates immunized with (4-hydroxy-3-nitrophenyl)acetyl coupled to chicken gamma-globulin than in those from neonates immunized with poly(L-Tyr,L-Glu)-poly-D,L-Ala-poly-L-Lys complexed with methylated BSA. Mutations were found in heavy chains lacking N regions, suggesting that B cells of the putative fetal lineage can somatically mutate and diversify an initially limited repertoire. Since neonates immunized as early as 1 or 2 days after birth had mutations, the somatic mutation machinery can be activated soon after birth, suggesting that early vaccination should result in affinity maturation and protective immunity in the neonate.     

Recovery of memory following amnesia in the rat and mouse.

Conducted 6 experiments with male Holtzman rats (n = 84) and male C57BL/6J strain mice (n = 278). Memory of 1-trial passive avoidance was disrupted by ECS or a protein synthesis inhibitor, cycloheximide. Results indicate that (a) reexposure of the amnesic S to the training apparatus was sufficient to initiate recovery, (b) a reminder shock catalyzed the rate of recovery of memory only when presented before or after reexposure to the training apparatus, (c) the recovered memory was as durable as the memory observed in Ss never treated with the amnesic agents, and (d) cycloheximide attenuated the recovery of memory in mice made amnesic by the same agent. This attenuation applied to memory recovered by reexposure to the apparatus alone or in combination with reminder shock given before or after the initial retention test. (15 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development of learning and memory of -maze training in neonatal mice.

Presented 25 trials in a shock-escape maze to 90 Swiss-Webster mice at 9, 11, or 13 days of age. One-half of the Ss at each age were trained to the goal opposite their 1st-trial choice, while the other 1/2 served as yoked controls. 24 hr. later, the trained groups received 25 additional trials to the previous goal. The yoked groups and groups without prior exposure were trained to the goal opposite their 1st-trial choice. 9-day-old Ss trained to a specific goal showed some improvement in performance during original training, while the 11- and 13-day-old groups demonstrated substantial improvement. On retention tests, 9-day-old Ss trained to the same goal on both days did not differ from either control group, but 11- and 13-day-old trained Ss were reliably better than either control group. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of thermoregulatory mechanisms in the rat.

The ability of rats to select a warm environment was studied as a function of postnatal age (birth to 13 days), using 100 Long-Evans hooded rats as Ss. Ss younger than 5 days demonstrated no choice response (movement to a warm compartment, 36-37 .C); however, they did demonstrate movement within the start compartment (23 .C). Increasing the motor capabilities of the pups, by injection of levodopa (50 mg/kg), elicited a choice response in 4-5 day-old Ss. Younger Ss demonstrated no choice of a warm environment even though they moved considerably. Also there was no difference between levodopa-treated and control Ss in the magnitude of temperature change in pups isolated from their mother for 1 hr. The evidence suggests development of behavioral thermoregulatory mechanisms prior to abilities for internal regulation. (22 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of morphine withdrawal in the rat.

The present studies examined behavioral changes during precipitated morphine withdrawal in 7- to 42-day-old rat pups. One group of rats was injected with morphine sulfate (10.0 mg/kg) twice daily for 6.5 days. Another group of 7-day-old rats received a lower dose of morphine (3.0 mg/kg). Controls were saline injected or untreated litters (7-day-old pups only). On Day 7, a target pup was injected with saline or naltrexone (0.3–20.0 mg/kg). Preweaning pups were observed in a warm chamber with the litter. Forty-two-day-old rats were tested individually. Morphine-treated pups tested with naltrexone showed significant alterations in behavior that varied at different ages. For example, rolling, stretching, and head and paw moves were observed at the younger ages, whereas burrowing, diarrhea, jumps, teeth chatter, and wet dog shakes occurred in the older rats. These data indicate that morphine-abstinent rats demonstrate withdrawal signs that are within the developmental repertoire of the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of beta-adrenoceptor/adenylyl cyclase desensitization mechanisms: the role of neonatal innervation

The ability of adrenergic stimulation to elicit desensitization of the beta-receptor/adenylyl cyclase signaling cascade is not an inherent property of cells but rather is acquired during the period in which sympathetic innervation develops. This study examines whether innervation provides the signal that enables target cardiac and hepatic cells to learn to desensitize their responses. Neonatal rats were sympathectomized with 6-OHDA on postnatal day 1 and were treated at various ages with a regimen of isoproterenol known to elicit desensitization in adults. In control rats, desensitization first appeared between days 6 and 15. Desensitization was heterologous, involving changes in the efficiency of G-protein coupling, as there were parallel decreases in isoproterenol-stimulated adenylyl cyclase activity, basal activity and fluoride-stimulated activity (maximal G-protein activation) without changes in forskolin-Mn2+-stimulated activity (total cyclase catalytic activity). The lesioned animals showed a delay in the onset of desensitization as isoproterenol did not evoke decreased responsiveness until day 25 in the heart; the liver did not display agonist-induced desensitization even at day 25. The effects of lesioning on development of desensitization were entirely separable from those on regulation of beta-receptors themselves: agonist-induced decreases in receptor binding appeared by day 15 in both control and lesioned animals. Uniquely in the youngest animals (6 days old), isoproterenol treatment produced heterologous sensitization of adenylyl cyclase responses rather than desensitization, with a parallel increase in basal, isoproterenol-, fluoride- and forskolin-Mn2+-stimulated activity; the latter indicates induction of total catalytic activity as the primary mechanism of sensitization. The lesioned neonates did not show sensitization, despite the fact that during this period, sympathetic pathways are not functionally competent. Our results indicate that innervation provides a timing signal for the onset of desensitization capabilities of sympathetic target cells, but is not absolutely required for the cells to learn how to desensitize. Prior to the onset of desensitization, agonists induce sensitization that may be important in preserving physiological responsiveness during ontogenetic surges of adrenergic activity. The absence of sensitization in lesioned animals implies that, before physiological function is completely established, early pioneer synapses provide a trophic signal that enables cells to increase their sensitivity to stimulation during the perinatal transition period.     

Induction and suppression of reagins in the neonatal mouse

Neonatal SWR mice are capable of synthesizing reagins when immunized with a mixture of concanavalin and ovalbumin or a mixture of Bordetella pertussis, alum and ovalbumin. Reaginic antibody-forming cells can be found in the spleen, lymph nodes, bone marrow and Peyer's patches. Tolerance with respect to IgE can be induced by the injection of deaggregated ovalbumin into neonatal mice.     

Ontogeny of the acoustic startle response in C57BL/6J mouse pups

A cross-sectional design was used to study the development of acoustic startle behavior in C57BL/6J mice from the approximate onset of hearing (12 days) to 17 days of age. Startle incidence and latency were recorded in response to 5-, 7-, 10-, 15-, and 20-kHz tones each presented at 80, 90, and 100 dB (SPL). From 12 to 17 days of age, higher frequency and lower intensity tones became increasingly effective in eliciting the acoustic startle response. In addition, startle latency decreased substantially, and response incidence became more sensitive to changes in tone intensity and tone frequency. This rapid ontogeny of the acoustic startle response closely parallels previously demonstrated neurophysiological development of the mouse pup auditory system.     

Ontogeny of meal patterns of the rat.

Two experiments, one with 6 18-60 day old female Wistar rats and the other with 12 Wistar and Long-Evans rats, examined the development of adult rat meal patterns. Although diurnal differences in food intake were present as early as 18 days after birth, with significantly more food being consumed in the dark, these differences were much smaller than those seen in adults. Nocturnal feeding gradually increased, reaching adult levels at around 6 wks of age. In general, little or no direct correlation was observed between meal size and postmeal interval length until rats were 4-5 wks old. Thereafter, correlations of +.40 or higher were usually observed. On the other hand, correlations averaging around zero were observed between meal size and premeal interval at all ages studied. Results are discussed in terms of their implications for proposed physiological mechanisms determining meal onset. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of cholinergic mediation of behaviors in the rat.

In 6 experiments with 159 immature Sprague-Dawley rats it was found that although scopolamine disrupted discriminative choice behavior in both 15- and 23-day-old pups, it increased latency to choice in 15-day-olds and decreased it in 23-day-olds. This disruption of discriminated choice behavior was not due to differential shock thresholds or differences in locomotor activity between drug-treated and control Ss, nor was it specific to a T-maze shock-escape discrimination task. Results suggest that central cholinergic mediation of different behaviors may mature at different rates. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term effects of selective neonatal temporal lobe lesions on learning and memory in monkeys.

Rhesus monkeys with neonatal damage to either the medial temporal lobe or the inferior temporal cortical area TE, and their normal controls, were reassessed in visual habit formation (24-hour intertrial interval task) and visual recognition (delayed nonmatching to sample [DNMS]) at 4–5 years of age and then tested on tactile and spatial DNMS. Results on the two visual tasks were the same as those obtained when the monkeys were under 1 year of age. Specifically, early medial temporal lesions, like late lesions, left habit formation intact but severely impaired recognition memory. Furthermore, the memory deficit extended to the tactile and spatial modalities. By contrast, early damage to TE, unlike late damage to it, yielded only mild deficits on both visual tasks and had no effect on tactile or spatial DNMS. Compensatory mechanisms that promote substantial and permanent recovery thus appear to be available after neonatal TE lesions but not after neonatal medial temporal lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioning in inbred mouse strains: An analysis of the time course of memory.

Three mouse strains were examined for short- and long-term memory for Pavlovian fear conditioning measured 1 hr and 24 hr after conditioning. Both DBA/2J and CBA/J mice exhibit reduced long-term memory for contextual fear conditioning compared with C57BL/6J mice. In cued fear conditioning, however, DBA/2J mice show reduced short- and long-term memory compared with C57BL/6J mice, whereas CBA/J mice exhibit reductions only in short-term memory. These results underscore the importance of examining the time course of memory retention, and they suggest that inbred mouse strains may provide a diversity of phenotypes. The results also suggest that the processes of short- and long-term memory storage as well as contextual and cued fear conditioning are dissociable and are mediated by genetically distinct neurobiological mechanisms. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny and sexual dimorphic expression of mouse type 2 11beta-hydroxysteroid dehydrogenase

During early neonatal life, important changes occur in the gut. The intestine is challenged by both milk and a microbial flora. Later on, at weaning, the diet of mice changes from milk to pelleted food leading to changes in microbial contents. This period seems essential for a complete development of the mucosal immune system. We investigated the development of both intraepithelial (IEL) and lamina propria lymphocytes (LPL), from day 5, and every 5 days, up to day 30 after birth. IEL and LPL were isolated from the small intestine and the phenotype was assessed by FACS analyses, using antibodies for detection of T-cell markers CD3, TCR alpha beta, TCR gamma delta, CD4, CD8 alpha, CD8 beta, CD5, CD18, CD54, and CD49d. Our data show a clear increase in the number of LPL just before weaning, while the number of IEL increased after day 15. A more mature pattern of membrane antigen expression of both IEL and LPL was observed at weaning. The adhesion molecules CD18, CD54, and CD49d, essential for cellular communication of lymphocytes, showed an expression peak at weaning. In conclusion, the mouse mucosal immune system develops during the first 3 weeks of neonatal life leading to the formation of a more mature immune system at weaning.     

Ontogeny of conditioned inhibition in domestic chicks.

Used the combined-cue test to measure age-dependent changes in learned stimulus inhibitory control in 40 young Vantress * Arbor Acre chicks trained to key peck for heat reinforcement. Both 1- and 4-day-old chicks were given either 96 or 384 discrete trials in a successive discrimination test, and then their response latencies to the novel combined cue (S+, S-) and the prior S+ cue were compared with those of age-matched controls during extinction. Major findings are as follows: (a) One-day-old chicks showed significant response suppression to the combined cue only after receiving 384 discrete trials, whereas 4-day-old chicks showed significant response suppression after both 96 and 384 trials. (b) While control chicks (S+ training only) of both age groups pecked more quickly at the novel cue than at the prior S+ cue during extinction, only the younger chicks pecked more quickly at the novel cue as the number of their prior S+ responses increased. The main conclusion from these experiments is that even the 1-day-old chick has the capacity to acquire learned inhibitory stimulus control but does so at a slower rate than the 4-day-old chick. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of defensive reactions in Norway rats.

In 3 experiments, 219 Sprague-Dawley albino rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. 20-day-old Ss were relatively unaffected by these events, while Ss aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. Data are consistent with R. C. Bolles's (1970, 1971) hypothesis that shock-elicited responses are innate defensive reactions. It is suggested that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of serotonergic inhibition of behavioral arousal in the rat.

Tested the effects of para-chlorophenylalanine (P-CPA), which depletes brain serotonin, in 3 experiments with 10-25 day old albino Sprague-Dawley rats. Experimental Ss were tested for locomotor effects 0, 24, 48, and 72 hrs after P-CPA injection. Depletion of serotonin increased behavior arousal in 15-, 20-, and 25-day-old Ss, but not in those 10 days old. P-CPA potentiated the locomotor activity induced by amphetamine, but again 10-day-old Ss did not show the effect. These results are interpreted as evidence for the delayed maturation of a serotonergic inhibitory system that modulates behavioral arousal. (53 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of neonatal thymectomy on follicle numbers in the post-natal mouse ovary

1. Surgical removal of the thymus gland within 48 hours of birth has no effect upon the numbers of small, medium and large ovarian follicles in Bagg albino strain mice during the first 12 weeks of life. 2. 20% of thymectomised mice more than 12 weeks of age developed ovarian atrophy which included the disappearance of corpora lutea and an overall reduction in all fractions of the follicle population. 3. These results do not support the proposal of Nishizuka and Sakakura that the thymus gland specifically maintains the non-growing, small (primordial) follicle pool in the mouse ovary during post-natal and reproductive life.     

Targeted disruption of the insulin receptor gene in the mouse results in neonatal lethality

Targeted disruption of the insulin receptor gene (Insr) in the mouse was achieved using the homologous recombination approach. Insr+/- mice were normal as shown by glucose tolerance tests. Normal Insr-/- pups were born at expected rates, indicating that Insr can be dispensable for intrauterine development, growth and metabolism. However, they rapidly developed diabetic ketoacidosis accompanied by a marked post-natal growth retardation (up to 30-40% of littermate size), skeletal muscle hypotrophy and fatty infiltration of the liver and they died within 7 days after birth. Total absence of the insulin receptor (IR), demonstrated in the homozygous mutant mice, also resulted in other metabolic disorders: plasma triglyceride level could increase 6-fold and hepatic glycogen content could be five times less as compared with normal littermates. The very pronounced hyperglycemia in Insr-/- mice could result in an increased plasma insulin level of up to approximately 300 microU/ml, as compared with approximately 25 microU/ml for normal littermates. However, this plasma level was still unexpectedly low when compared with human infants with leprechaunism, who lack IR but who could have extremely high insulinemia (up to > 4000 microU/ml). The pathogenesis resulting from a null mutation in Insr is discussed.     

Effects of selective neonatal hippocampal lesions on tests of object and spatial recognition memory in monkeys.

Earlier studies in monkeys have reported mild impairment in recognition memory after nonselective neonatal hippocampal lesions. To assess whether the memory impairment could have resulted from damage to cortical areas adjacent to the hippocampus, we tested adult monkeys with neonatal focal hippocampal lesions and sham-operated controls in three recognition tasks: delayed nonmatching-to-sample, object memory span, and spatial memory span. Further, to rule out that normal performance on these tasks may relate to functional sparing following neonatal hippocampal lesions, we tested adult monkeys that had received the same focal hippocampal lesions in adulthood and their controls in the same three memory tasks. Both early and late onset focal hippocampal damage did not alter performance on any of the three tasks, suggesting that damage to cortical areas adjacent to the hippocampus was likely responsible for the recognition impairment reported by the earlier studies. In addition, given that animals with early and late onset hippocampal lesions showed object and spatial recognition impairment when tested in a visual paired comparison task, the data suggest that not all object and spatial recognition tasks are solved by hippocampal-dependent memory processes. The current data may not only help explain the neural substrate for the partial recognition memory impairment reported in cases of developmental amnesia, but they are also clinically relevant given that the object and spatial memory tasks used in monkeys are often translated to investigate memory functions in several populations of human infants and children in which dysfunction of the hippocampus is suspected. (PsycINFO Database Record (c) 2011 APA, all rights reserved)