Developmental environment: variables important for later learning and changes in cholinergic activity

Environmental experience of developing rats was manipulated in two ways. These were (1) providing increments in amount of visual stimulation vs. increased variety of novelty of visual stimulation, and (2) informal experience vs. formal training in discriminating between the given stimuli. At the conclusion of the developmental treatment an index of performance change was obtained by testing discrimination learning on a Lashley Jumping Stand. Effects on the cholinergic system, specifically, acetylcholinesterase (AChE) and cholinesterase (ChE) activities, were also examined. Increments in variety of stimulation, but not increases in amount, were found to contribute significantly to observed differences in AChE and ChE activity and in learning performance. Formal training in addition to enriched informal experience added little to either the biochemical effects or to the observed improvement in performance on the relevant learning task.     

The influence of nutrition on neural and behavioral development. 3. Development of some motor, particularly locomotor patterns during infancy

The locomotor development of infant rats nursed by mothers that had free access to food during lactation or were fed during that period 40% or 20% of the ad lib diet were compared. The “spontaneous” emergence or disappearance of several locomotor patterns were sampled daily in an open field situation, and the development of others was studied by inducing them in test situations. The spontaneous motor patterns included general locomotor activity, pivoting, head lifting, and standing on the hindlegs. The induced activities were hanging and moving on a suspended horizontal string, clinging to and descending on vertical ropes, climbing up on a rod, and homing in various test situations. The motor performance of the severely undernourished animals (offspring of mothers on a 20% diet) was inferior to normals in all the observations. This was manifested most commonly in reduced frequency or speed in the performance of certain acts, and in some cases in the prolonged persistence of infantile motor patterns or a delay in the appearance of more advanced patterns.     

肠道营养支持对烧伤大鼠肠粘膜屏障功能的保护作用及其机理

观察不同营养支持途径地严重烧伤所致肠粘膜屏障功能损害的影响并探讨其机制。采用30％体表面积Ⅲ度烧伤大鼠模型,随机分成正常对照（Control),静脉营养（PN）及肠道营养（EN）组,观察了烧伤后肠粘膜屏障功能的变化及PN和EN对其的影响,结果显示,烧伤后肠粘膜通透性,血浆二胺氧化酶（DAO）活性明显高于对照组（P＜0．01）,而肠上皮细胞增殖指数,肠三叶因子（ITF）含量,肠粘液层厚度及己糖和唾液酸的含量则明显降低（P＜0．05）,同PN相比,EN对上述指标均有一定的逆转作用,提示EN较PN更有利于减轻肠粘膜受损程度,促进肠粘膜修复。     

Effects of prenatal nutrition on learning and motivation in rats.

The results of two learning experiments revealed that adult male rats whose dams suffered either prenatal zinc deficiency or undernutrition showed, as compared to rats whose dams were fed ad lib, normal diets during pregnancy (1) more resistance to extinction following partial reinforcement, and (2) a faster occurring negative contrast effect when shifted from large to small reward. An incentive-motivation interpretation of the data suggests that the nutritionally deprived and normal animals differ with respect to the incentive value of the consummatory reward. This effect appears to be long-term.     

Strain-differentiated circadian and ultradian rhythms in locomotor activity of the laboratory rat

Spontaneous locomotor activity (LA) was recorded in five inbred strains of laboratory rats (ACI/Ztm, AS/Ztm, BH/Ztm, BS/Ztm, LEW/Ztm) under light-dark (LD 1212), continuous-dark (DD), and continuous-light (LL) conditions. Strain-dependent differences in LA were observed under each light condition. Under LD conditions, 24-h rhythms were found in the LA pattern of each strain studied. In addition, the BH strain showed a clear bimodal, and the LEW strain a trimodal, activity pattern. Spectral analysis of the activity patterns revealed distinct 4- and 4.8-h ultradian rhythms in the LEW strain and 12-, 6-, 4.8-, and 4-h rhythms in the BH strain. These strain-characteristic patterns persisted under continuous-dark conditions, therefore demonstrating their endogenous character. Under continuous-bright-light conditions the circadian rhythms decreased to a non-significant level in the AS and BS strains. This was not the case, however, in all animals of the LEW and BH strains. Despite the rapid decrease in the 24-h rhythm under LL, the LEW and BH strains showed significant ultradian rhythms.This work was supported by a grant from Deutsche Forschungsgemeinschaft (SFB 146).     

Environmental influences on brain and behavior of year-old rats

The brains of rats, almost a year old, were found to be similarly susceptible to the influences of differential housing as had been those of weanling rats. In 3 experiments, male S₁ rats, about 285 days of age, remained for 30, 60, or 90 days in enriched (EC), impoverished (IC), or standard colony (SC) conditions before sacrifice for measures of weights and enzymatic activities of standardized brain sections. Occipital and total cortical brain weights increased significantly after EC, whereas subcortical regions seemed to be resistant to environmental influences. Year-old rats responded with greater cortical weight increases and enhanced occipital cholinesterase activities from a period of enrichment extended beyond 60 days than SC agemates. The cortices of IC rats, in contrast, showed a decline in weights with longer duration in isolation. Environmental enrichment, furthermore, disposed year-old rats to faster learning in the Lashley III maze.     

Amount of feeding activity and size of meals in free-feeding rats

Instrumentation is described for simultaneous measurement of feeding duration (time actually spent feeding during a nominal meal) and weight of food eaten in individual meals throughout 24-hr periods in free-feeding rats. These variables were measured in two rat strains. Meal weight cannot usefully be estimated directly from meal duration (total time from beginning to end of a nominal meal) or from meal feeding duration. An adjustment procedure is described that removes systematic error and allows a useful estimate to be made from meal feeding duration. The discrepancy remaining between measured and estimated meal size is quite large and is a measure of the independence of control of food intake and control of the behavioral output of feeding.     

Distinct patterns of hippocampal formation activity associated with different spatial tasks: a Fos imaging study in rats

Fos levels were measured in rats trained in one of two qualitatively different spatial memory tasks in a water maze. In one task, (landmark condition) rats found a submerged platform that was always 25 cm south of a visible landmark, the absolute position of the platform and landmark changing after every trial. In the other task (place condition), rats swam to a platform that remained in the same absolute position on every session, but changed session to session, with this task relying on the memory of allocentric cues. Despite matched swim times, the landmark condition resulted in higher levels of Fos in a wide range of cortical and subcortical sites, including the hippocampus and its connections. Structural equation modelling revealed two different patterns of hippocampal function. In the allocentric place task there was a significant association between Fos activity in the entorhinal cortices and the hippocampus proper, while in the non-allocentric landmark task this relationship was not present, but was replaced by a connection from the entorhinal cortices to the subiculum. Thus, the two different tasks engage two different modes of hippocampal activity as demonstrated by Fos expression.     

Cardiorespiratory regulation and activity patterns of rat pups studied with their mothers during the nursing cycle

Rat pups aged 10 to 19 days were implanted with chronic electrodes and recorded while freely moving in the litter situation, during nursing and throughout naturally occurring maternal absences. Heart rates were significantly higher in the mother's presence (p<.01) while respiratory rates and percent of time spent active were identical under the 2 conditions. Pups' inactive heart rates progressively increased during the 20 min of nursing, while no such time trends were evident in other measures. Inactive heart rates decreased significantly (p<.01) as a function of age; respiratory rates and activity during nursing showed similar trends. A histogram of number of periods of activity bursts of different durations while pups were nursing showed a preponderance of 1- to 5-sec bursts which were observed to be associated with active sucking and pawing movements. This pattern of short bursts of spontaneous activity was repeated almost identically when the mother was absent, although the behavior was qualitatively different. In a second experiment, increases in pups' body temperature of .2°C to 1.0°C were found to accompany active nursing. If such increases were imposed by an artificial heat source, heart rates of pups actually fell slightly. In a third study, heart rates were recorded from nursing mothers and found to be relatively unaffected by stimulation from the pups.     

The influence of nutrition on neural and behavioral development. II. Growth of body and brain in infant rats using different techniques of undernutrition

Two techniques were used for producing undernutrition in infant rats and their effects on the growth of the body and the brain were investigated. In one procedure, the mothers were fed ad lib and the size of their litters was varied (5, 10, and 16 pups). In the other, litter size was kept constant at 8 pups per mother but during lactation the mothers either were fed ad lib or their food intake was restricted to 40% or 20% of normal consumption. The latter procedure was found to be the more reliable way of producing experimental retardation in the growth of the body and of the brain during the preweaning period. The failure of both procedures in producing retardation of brain growth during the first week of life is discussed.     

Early life handling decreases serotonin turnover in the nucleus accumbens and affects feeding behavior of adult rats

In our previous studies, we reported that neonatally handled rats have an increased ingestion of sweet food but are resistant to the damaging effects of a chronic exposure to a highly palatable diet. Accumbal serotonin (5‐HT) is important for feeding behavior and plays a role in the vulnerability to diet‐induced obesity. Therefore, our hypotheses were (1) 5‐HT turnover in the nucleus accumbens is altered in neonatally handled animals and plays a role in their differential feeding behavior and (2) if this is so, a chronic pharmacological treatment affecting 5‐HT reuptake (chronic imipramine) would be able to revert the behavioral findings. Litters were divided into nonhandled and handled (10 min/day, Days 1–10 after birth). In Experiment 1, we demonstrated that a decreased 5‐HT metabolism in the nucleus accumbens was observed in adult handled animals. In Experiment 2, the two previous groups were subdivided and assigned to receive imipramine diluted in water or water alone. After 30 days of treatment, we evaluated their weight gain and feeding behavior. Handled rats weighed less than nonhandled rats, and all imipramine‐treated rats showed a reduction in weight gain after 60 days of treatment. Imipramine reverted the increased sweet food consumption seen in neonatally handled rats. We conclude that serotonin is involved in the altered feeding behavior of neonatally handled rats, and this protocol is an important tool for studying the mechanisms by which early life events have a long‐term impact on feeding preferences. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52:190–196, 2010     

短期丰富生存环境增加中老年雄性大鼠海马结构内有髓神经纤维的总长度

目的探讨短期丰富生存环境干预对正常中老年雄性大鼠海马结构及海马内有髓神经纤维的影响。方法将20只14月龄的雄性SD大鼠随机分为丰富生存环境组与空白对照组,前者在丰富生存环境条件下饲养4个月,后者在普通环境中饲养4个月后,采用Morris水迷宫测试两组大鼠的空间学习能力;运用透射电子显微镜和体视学方法对两组大鼠海马结构及海马内有髓神经纤维进行定量研究。结果丰富生存环境组大鼠空间学习能力与空白对照组之间不存在显著性差异;丰富生存环境组与空白对照组相比较,海马结构总体积两组间无显著性差异。丰富生存环境组海马结构内有髓神经纤维的总体积、有髓神经纤维总长度、有髓神经纤维平均直径显著增加。结论短期丰富生存环境干预对14月龄雄性大鼠海马有髓神经纤维具有显著性影响。这一研究结果为将来寻找延缓大脑衰老进程的行为学手段提供了重要的理论依据。     

短期丰富生存环境对中老年雌性大鼠海马结构及其内有髓神经纤维的影响

目的 探讨短期丰富生存环境干预对中老年雌性大鼠海马结构及其内有髓神经纤维的影响。 方法 将20只14月龄的雌性SD大鼠随机分为丰富生存环境组和标准环境组,每组各10只,对丰富生存环境组的动物给予4个月丰富生存环境干预, 标准环境组于普通标准环境下饲养4个月;然后每组各随机选取5只,采用Morris水迷宫对大鼠的空间学习能力进行测试,然后运用透射电子显微镜和体视学方法分别对大鼠大脑海马结构及其内有髓神经纤维进行定量研究。 结果 短期丰富生存环境组中老年雌性大鼠与标准环境组相比,其空间学习能力明显增强;丰富生存环境组海马结构内有髓神经纤维总长度和总体积分别显著增加了43.4%和47.4%,且有髓神经纤维总长度的增加主要是由于细小直径的有髓神经纤维长度增加所致。海马结构总体积和海马结构内有髓神经纤维直径未见改变。 结论 4个月丰富生存环境干预对于14月龄雌性大鼠空间学习能力、海马内有髓神经纤维均有显著性影响。     

Genetic analysis of circadian and ultradian locomotor activity rhythms in laboratory rats

Obvious differences exist in the daily activity patterns of the LEW/Ztm and ACI/Ztm inbred strains of laboratory rats. The inbred strain ACI/Ztm shows a clear 24-h rhythm of locomotor activity. The activity pattern of the LEW/Ztm strain, however, is characterized by ultradian rhythms of 4- and 4.8-h periods. Genetic analysis of crosses between the two strains was used to examine the relative amounts of additive genetic and dominance effects for traits associated with circadian and ultradian rhythms of locomotor activity. The measured variables of the timing mechanism (amplitude c; acrophase ; 24, 4.8-, and 4-h spectral estimates) exhibited substantial heritability, with general dominant-recessive modes of inheritance and the associated dominance variance.This research was supported by Grant SFB 146 from the Deutsche Forschungsgemeinschaft.     

Development of behavior in the litter huddle in rat pups: Within‐ and between‐litter differences

Early postnatal growth in mammals can be considerably influenced by litter size and often differs among littermates in relation to birth mass. In a study of Long Evans laboratory rats we asked whether within‐ and between‐litter differences in body mass and growth are related to behavioral development during early postnatal life. For this, we analyzed the amount of general motor activity and the display of directed, seemingly goal‐oriented interactions within the litter huddle in previsual pups. During the study period from postnatal days 2 to 11, we found significant changes in pup behavior, showing a nonlinear, quadratic shape. General motor activity and, more specifically, the display of behaviors apparently directed to reaching central positions in the litter huddle increased during the first postnatal days and then decreased again. However, pups from small litters that grow more rapidly than pups from large litters, showed a faster increase in both behaviors, whereas the young from large litters reached a higher maximum. We also found striking within‐litter differences in the amount of directed behavior performed by light and heavy pups, with higher levels in the former group, most probably because light pups that have a less favorable body mass‐to‐volume ratio and more often occupy peripheral positions in the litter huddle, make a greater effort to reach thermally favorable central positions. In conclusion, our study shows there to be consistent between‐litter as well as within‐litter differences in behavioral patterns during early life. These differences might have important implications for an individual's long‐term behavioral and physiological performance. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 52: 35–43, 2010     

Morris水迷宫训练后即早基因c-Fos及c-Jun在大鼠丘脑前核的表达

目的为探讨Morris水迷宫训练后丘脑前核内c-Fos和c-Jun的表达。方法 30只成年大鼠均分为正常组,假训练组和Morris水迷宫训练组,通过免疫组化和WesternBlot检测c-Fos和c-Jun的表达。结果 Morris水迷宫训练组丘脑前核c-Fos表达水平与假训练组和正常组比较明显增强(P<0.05),丘脑前背侧核显著强于前腹侧核(P<0.05)。训练组c-Jun表达水平与假训练组和正常组比较明显增强(P<0.05)。结论 c-Fos和c-Jun可能参与空间学习记忆过程。     

Involvement of sympathetic function in the sleep-related change of gastric myoelectrical activity in rats

The gastric myoelectrical activity (GMA) fluctuates across sleep–wake states as a result of modulation by the brain–gut axis. The role of the autonomic nervous system in this phenomenon, however, was not elucidated fully. Through simultaneous recording and subsequent continuous power spectral analysis of electroencephalogram, electromyogram, electrocardiogram and electrogastromyogram (EGMG) in 16 freely moving Wistar rats, the sleep–wake states of the animals were defined and indices of cardiac autonomic regulation and GMA were calculated. We found that both cardiac autonomic regulation and GMA fluctuated through sleep–wake cycles. Correlation analysis further revealed significant correlations between EGMG power and each of the R–R interval, high-frequency power, low-frequency power, very-low-frequency power, low-frequency power to high-frequency power ratio and normalized low-frequency power of heart rate variability with respect to their trend of change across different sleep–wake states. These results suggest that the sleep–wake-related change of GMA was related to sympathovagal balance. The sympathetic nerve may play a more important role in the central modulation of GMA than perceived previously.     

Circadian patterning of feeding,drinking and activity during diurnal food access in rats

Using an “ecologically” relevant approach, the present study investigated (1) the association between feeding and drinking patterns and their circadian organization and (2) changes in general activity (or life-style), during ad lib conditions (fa:LD) and in a situation where access to food was restricted to the light phase (fa:L). Rats were housed in large outcages with nest boxes. Feeding, drinking, activity, outcage and nest occupation were recorded automatically throughout the day-night cycle. Access to food was restricted by a sliding door situated in front of the food hopper. Under ad lib conditions rats were mainly nocturnal, eating 94% and drinking 95% of their daily intakes at night. The patterns of food and water intake were similar, showing a bimodal distribution over the dark phase. During fa:L rats showed an initial large peak in feeding with lights on, followed by a long pause. Thereafter, feeding activity was variable but remained at a low level. The nocturnal drinking pattern persisted. However, 17.5% of daily water intake was meal-associated, compared with 71% during ad lib. Diurnal activity was associated with feeding and nocturnal activity with drinking. Nocturnal outcage and nest occupation patterns were not shifted to the light phase. The experiment demonstrates that rats on an fa:L schedule reduce food and water intake, and body weight, while still retaining circadian characteristics in the temporal distribution of drinking, activity, outcage and nest occupation. Further, although feeding and drinking may be causally related they need not occur in close temporal association. The rapidity of re-establishment of the normal feeding pattern, on return to free-feeding, and the close association with drinking under normal conditions, suggest the existence of a single or two coupled oscillators controlling feeding and drinking.