Taste aversion learning in preweanling rats exposed to alcohol prenatally

The effects of prenatal alcohol exposure on the development of a conditioned taste aversion were examined in preweanling rat pups. Mothers of these pups were fed isocaloric liquid diets containing either 35 or 0% ethanol-derived calories (EDC) from gestation days 6 through 20. A pair-feeding procedure was employed, and an ad lib lab chow control group was also included. At 5, 10, or 15 days of age, pups were infused with a saccharin solution through a cannula implanted in the oral cavity. Half of the pups in each group were then injected with lithium chloride (LiCl), which served as the poisoning agent, and the other half with sodium chloride (NaCl) as a control. Animals were subsequently tested for a conditioned aversion to the saccharin solution. At 15 days of age, all of the pups in the LiCl-poisoned group demonstrated a conditioned taste aversion to the saccharin solution, but the degree of this aversion was less in alcohol-exposed offspring. At 10 days of age, a taste aversion was learned, although it was not as strong as that shown by 15-day-old pups, and it appeared to be learned equally well by all of the prenatal treatment groups. At 5 days of age, there was marginal support for taste aversion learning. Again, it did not interact with prenatal treatment. The ontogenic differences in taste aversion learning exhibited by alcohol-exposed offspring relative to controls are discussed in terms of altered hippocampal development.     

The effect of dorsal and ventral hippocampal lesions on short-term memory in cats]

The influence of lesion of the dorsal and ventral hippocampus on short-term memory was studied by the method of delayed conditioned reactions. It has been shown that after lesion of the dorsal hippocampus the delay considerably increases and that subsequent lesion of the ventral hippocampus completely eliminates delayed reactions. A conclusion has been drawn that the dorsal hippocampus has an inhibitory influence and the ventral hippocampus a facilitating effect on short-term memory. However the existence of a modulating effect does not imply that the hippocampus is a specific substrate of memory. A considerable part in the mechanism of memory is also played by other brain structures, which are activated together with the hippocampus. Particular importance is attached to activation of the bentromedial and lateral hypothalamus and the cortical associative areas.     

Psycho-emotional manifestations in rats with hippocampal lesions

The study aimed at revealing psycho-emotional manifestations of Wistar rats in a problem situation when they had to solve a food-getting task in a multi-alternative maze. Bilateral lesion of dorsal hippocampus did not affect the learning process while the pattern of psycho-emotional manifestations changed in all the animals irrespective of their individual properties. The pverall effect was manifested in flatness of psycho-emotional responses as a result of reduction of extreme forms of both passive and active stress responses. Individual effects depended on the behavioural phenotype. Hippocampus lesion in initially excitable rats (10%) resulted in reduction of active stress responses (act/pass = 0.35/0.5 instead of 1.0/0.4 in control). Hippocampus lesion in initially inhibited rats (30%) did not affect the basic pattern of psycho-emotional responses, while in the rats with initially depressed cognitive activity (60%) it resulted in decreasing of passive and increasing of active stress responses (act/pass = 0.45/1/4 instead of 0.3/1.9). The findings suggest that hippocampus takes part in the psycho-emotional responses while the individual psycho-emotional pattern is determined by the morpho-functional features responsible for organisation of a psycho-emotional condition.     

Long-delay learning in rats with parabrachial pontine lesions

Two experiments were conducted to test the hypothesis that ratswith lesions in the parabrachial nucleus of the pons (PbN) canacquire conditioned taste aversions only if the conditionedand unconditioned stimuli are presented close together in time.In experiment 1, rats with lesions in the medial PbN, lateralPbN or outside of the PbN (lesioned control), and unoperatedcontrol rats were trained to avoid Na-saccharin in a one-bottletest. In this procedure, a 5-min delay was imposed between the15-min Na-saccharin presentation and an injection of LiCl (0.3M, 1 % body weight, i.p.). Results showed that, after threeNa-saccharin-LiCl pairings, all rats, except the medial PbNgroup, acquired a strong aversion to Na-saccharin. In experiment2, the same rats were presented with LiCl (0.12 M) in their15-min daily access to fluid on 3 alternate days. Although ratsin the medial PbN group drank more LiCl on day 1 than rats inthe other groups, they significantly reduced their LiCl consumptionon day 2 and did not differ from other groups by day 3. Resultsare discussed in terms of possible behavioral and physiologicalmechanisms that might account for these phenomena.     

Context codes and the effect of noisy learning on a simplified hippocampal CA3 model

This paper investigates how noise affects a minimal computational model of the hippocampus and, in particular, region CA3. The architecture and physiology employed are consistent with the known anatomy and physiology of this region. Here, we use computer simulations to demonstrate and quantify the ability of this model to create context codes in sequential learning problems. These context codes are mediated by local context neurons which are analogous to hippocampal place-coding cells. These local context neurons endow the network with many of its problem-solving abilities. Our results show that the network encodes context on its own and then uses context to solve sequence prediction under ambiguous conditions. Noise during learning affects performance, and it also affects the development of context codes. The relationship between noise and performance in a sequence prediction is simple and corresponds to a disruption of local context neuron firing. As noise exceeds the signal, sequence completion and local context neuron firing are both lost. For the parameters investigated, extra learning trials and slower learning rates do not overcome either of the effects of noise. The results are consistent with the important role played, in this hippocampal model, by local context neurons in sequence prediction and for disambiguation across time.     

Optimization of the touchscreen paired-associate learning (PAL) task for mice and its dorsal hippocampal dependency

Two versions of the touchscreen paired-associate learning (PAL) task have been developed for rodents: same PAL (sPAL) and different PAL (dPAL). These tasks are very important in studying murine models of Alzheimer’s disease and schizophrenia, and have also been used to test object-location memory in various studies. However, the relatively long time needed for the tasks (approx. 50 days for mice) limits their widespread use. By giving training that was more intensive with a higher number of trials, we shortened the time required for learning saturation in sPAL and dPAL to about one-third of the time required for the generally used protocol. Furthermore, by applying a reduced number of objects and trial types for sPAL, we developed a simplified version of sPAL, termed 2-object sPAL, in which mice could reach the fully learned level in 6 days. Our pharmacological experiments indicate that the dorsal hippocampal CA1 region is crucial for the performance of the two PAL tasks with the new protocols and the new 2-object sPAL. This work has significantly enhanced the usefulness of the touchscreen PAL tasks to increase the speed of learning, but they remain highly hippocampus-dependent object-location memory tasks.     

N-Acetyl-aspartyl-glutamate in the rat dorsal striatum: topographical distribution and effect of sensorimotor cortex lesions

The dipeptide N-acetyl-aspartyl-glutamate (NAAG) has been proposed as putative neurotransmitter of some corticostriatal projections. To further explore this possibility, endogenous NAAG levels were measured in various microdissected striatal regions in normal animals and in those with bilateral lesion of sensorimotor cortex. In intact rats there was a rostro-caudal gradient for NAAG, with highest concentrations in the more caudal portions of the striatum without significant differences between the medial and lateral regions. Decortication induced no significant changes in peptide concentration in any of the striatal regions or in the respective crude synaptosomal (P2) fractions. However, decorticated animals showed a large degree of deafferentation as evidenced by a marked and significant decrease in [³H]glutamate uptake as well as in glutamate levels measured in striatal homogenates or in crude synaptosomal fractions. No changes in striatal dopamine levels were observed in lesioned animals. Thus, these findings are not in favor of the existence of corticostriatal projections arising from the sensorimotor cortex using NAAG as neurotransmitter.     

滋肾方对衰老大鼠模型学习记忆能力的影响

目的 :观察滋肾方对亚急性衰老大鼠学习记忆及海马组织胆碱酯酶 (CHE)和单胺氧化酶 (MAO)的影响 ,以探讨滋肾方抗衰老的作用。方法 :持续注射D 半乳糖法致亚急性衰老大鼠模型 ,“Y”型电迷宫法进行学习记忆观察 ,并对海马组织进行酶学测定。结果 :滋肾方可以减少大鼠达标所需的电击次数 (P <0 .0 1) ,提高大鼠海马组织中胆碱酯酶活性 (P <0 .0 5 ) ,降低大鼠海马组织中单胺氧化酶活性 (P <0 .0 1)。结论 :滋肾方可以提高衰老大鼠学习记忆能力 ,其作用机制可能与提高大鼠海马组织中胆碱酯酶活性、降低单胺氧化酶活性有关     

Erythrocyte aging: a comparison of model systems for simulating cellular aging in vitro

Senescent cell antigen (SCANT) is a "neo antigen" that appears on the surface of normal old cells and initiates IgG binding and cellular removal. To investigate the mechanism by which SCANT is generated from its parent molecule, band 3, we subjected intact human erythrocytes to treatments that have been reported to result in changes in band 3 and/or to mimick aging in vitro. The validity of these treatments as model systems for erythrocyte aging was evaluated using a "red cell aging panel" that provides a biochemical profile of a senescent red cell. Treatments were assessed for their ability to induce in vitro the following changes observed in normal erythrocytes aged in vivo: 1 increased breakdown of band 3 as detected by immunoblotting, 2 decrease in anion transport efficiency as detected with a sulfate self-exchange assay, 3 decrease in total glyceraldehyde 3-phosphate dehydrogenase activity with an increase in membrane-bound activity, and 4 increase in the binding of autologous IgG as detected with a protein A binding assay. Neither incubation with the free radical-generating xanthine oxidase/xanthine system, nor treatment with malondialdehyde, and end product of free radical-initiated lipid (per)oxidation, results in age-specific changes. Loading of the cells with calcium and oxidation with iodate results in increased breakdown of band 3, but does not lead to increased binding of autologous IgG. Only erythrocytes that have been stored for 3-4 weeks show the same structural and functional changes as observed during aging in vivo.     

Proteome-wide characterization of seed aging in Arabidopsis: a comparison between artificial and natural aging protocols

A variety of mechanisms have been proposed to account for the extension of life span in seeds (seed longevity). In this work, we used Arabidopsis (Arabidopsis thaliana) seeds as a model and carried out differential proteomics to investigate this trait, which is of both ecological and agricultural importance. In our system based on a controlled deterioration treatment (CDT), we compared seed samples treated for different periods of time up to 7 d. Germination tests showed a progressive decrease of germination vigor depending on the duration of CDT. Proteomic analyses revealed that this loss in seed vigor can be accounted for by protein changes in the dry seeds and by an inability of the low-vigor seeds to display a normal proteome during germination. Furthermore, CDT strongly increased the extent of protein oxidation (carbonylation), which might induce a loss of functional properties of seed proteins and enzymes and/or enhance their susceptibility toward proteolysis. These results revealed essential mechanisms for seed vigor, such as translational capacity, mobilization of seed storage reserves, and detoxification efficiency. Finally, this work shows that similar molecular events accompany artificial and natural seed aging.     

强制运动促进成年大鼠海马齿状回神经发生并提高学习能力

为了探讨强制运动对成年大鼠海马齿状回（dentate gyrus,DG）神经发生的影响,强制大鼠在马达驱动的转轮中跑步,用5-溴-2-脱氧尿苷（5-bromo-2-deoxyuridine,BrdU）标记增殖细胞,巢蛋白（neuroepthelial stem cell protein,nestin）标记神经干细胞／前体细胞,然后用免疫细胞化学技术检测大鼠DG中BrdU及nestin阳性细胞。为了解强制运动后DG增殖细胞的功能意义,采用Y-迷宫检测大鼠的学习能力。结果表明,强制运动组DG中BrdU及nestin阳性细胞数均日月显多于对照组（P〈0．05）：强制运动对DG神经发生的效应有强度依赖性。Y-迷宫检测结果显示,强制运动能明显改善大鼠的学习能力。结果提示,在转轮中进行强制跑步能促进成年火鼠DG的神经发生,并改善学习能力。     

Alterations in dopaminergic modulation of prefrontal cortical acetylcholine release in post-pubertal rats with neonatal ventral hippocampal lesions

Excitotoxic lesion of the ventral hippocampus in neonatal rats is a putative animal model of schizophrenia with characteristic developmental abnormalities in dopaminergic neurotransmission and prefrontal cortical functions. Converging evidence also points to the involvement of the central cholinergic system in neuropsychiatric disorders. These two neurotransmitter systems are interlinked in the prefrontal cortex (PFC) where dopamine stimulates acetylcholine (ACh) release. In the present study, we investigated the role of dopamine in the developmental regulation of prefrontal cortical ACh release and the expression of nicotinic and muscarinic receptors in pre- and post-pubertal rats with neonatal ibotenic acid-induced lesions of the ventral hippocampus (NVH). In vivo microdialysis in the PFC revealed that systemic injections of the D(1)-like receptor agonist (+/-)-6-chloro-7,8-dihydroxy-1-phenyl2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide (SKF 81297) (2.5 and 5.0 mg/kg i.p.) caused significantly higher ACh release in post-pubertal NVH-lesioned animals (250 and 300% baseline for 2.5 and 5.0 mg/kg, respectively) compared with post-pubertal shams (150 and 220% baseline for 2.5 and 5.0 mg/kg, respectively). Most interestingly, while prefrontal cortical perfusion of SKF 81297 (100 and 250 microM) had no significant effect on ACh release in post-pubertal sham-operated animals, it significantly stimulated ACh release to approximately 250% baseline at both doses in post-pubertal NVH-lesioned animals. Receptor autoradiography demonstrated a significant and selective increase in M(1)-like receptor binding sites in the infralimbic area of the PFC in the post-pubertal NVH-lesioned animals. For all experiments, significant differences between sham and NVH-lesioned animals were observed only in post-pubertal rats. These results suggest a developmentally specific reorganization of the prefrontal cortical cholinergic system involving D(1)-like receptors in the NVH model.