Maturation of long-term potentiation in the hippocampal dentate gyrus of the freely moving rat

The ability of the perforant path/dentate granule cell synapse of the hippocampal formation to establish and maintain enhanced levels of synaptic transmission in response to tetanization (long-term potentiation, LTP) was investigated in freely moving rats at 15, 30, and 90 days of age. Measures of (1) the slope of the population excitatory postsynaptic potential (EPSP), and (2) the population spike amplitude (PSA) obtained before, and at several times following tetanization, were used to evaluate the magnitude and duration of LTP as a function of age. Significant enhancement of both EPSP slope and PSA measures was obtained from animals of all three ages in response to perforant path tetanization. The initial degree of enhancement was essentially the same across the age groups, ranging from +27% to +38% of pretetanization levels for EPSP slope measures and +60% to +75% of pretetanization levels for PSA measures, obtained 15 min after tetanization. The duration of this enhancement obtained from animals of the preweaning group was significantly longer than that obtained from either 30- or 90-day-old animals. Enhanced measures of both EPSP slope and PSA decayed to baseline levels in these older animals 18 to 24 h after tetanization, while animals tetanized at 15 days of age maintained potentiated levels of both measures for a period of 5 days following tetanization. Tetanization of 15-day-old animals resulted in a significant reduction in the latency to EPSP onset without affecting the time-based relationships among the other measured parameters, which included latency of the population spike onset, population spike minimum, and population spike offset. Tetanization had no effect on the latency measure of any of these parameters in either of the two older age groups. The primarily postnatal development of the dentate granule cell population suggests that both functionally immature GABAergic modulation of granule cell activity and the differential development of components of the N-methyl-D-aspartate receptor complex may be involved in the age-related differences in the induction and expression of the LTP phenomenon. This study represents the first developmental characterization of LTP in the perforant path/dentate granule cell synapse in freely moving rats during early development. The results indicate that LTP can be reliably established and maintained in behaving rats as young as 15 days of age. Whereas the degree of potentiation at this age is equivalent to that obtained from juveniles and young adults, the duration of the effect significantly outlasts that obtained from older animals in which development of the dentate gyrus is more functionally mature. © 1994 Wiley-Liss, Inc.     

Severe early malnutrition and DRL performance in the rat

Rats with a history of severe early malnutrition (6% casein) were compared to well-fed control animals on an ascending series of DRL values ranging from 5 to 60 seconds. The 6% rats who were dietarily-rehabilitated at weaning did not differ from control animals in efficiency, responses per reinforcement or response rate. In contrast, rats chronically exposed to 6% diets performed so poorly during training with continuous reinforcement that they did not advance to even the first DRL (5-sec) condition. These findings show that severely-undernourished rats can perform within normal limits on even high DRL values, provided they are well trained and that they have adequate nutritional rehabilitation.     

Modulation of paired-pulse responses in the dentate gyrus: effects of prenatal protein malnutrition

Since our major hypothesis is that prenatal protein malnutrition significantly affects hippocampal neuroplasticity, this study examined the effects of prenatal protein malnutrition on the modulation of dentate granule cell excitability in freely moving rats at 15, 30 and 90 days of age across the vigilance states of quiet waking (QW), slow-wave sleep (SWS) and rapid eye movement (REM) sleep. Using paired-pulse stimulation, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability elicited by stimulation of the medial perforant path, was obtained for each vigilance state at each stage of development. Four specific measures of granule cell excitability were computed, namely, PPI using both population spike amplitude (PSA) and EPSP slope measures, absolute values of PSA(1) and EPSP(1) slope. PPI values obtained at 15, 30 and 90 days of age, however, were altered during normal ontogenetic development, but not by vigilance state. At 15 days of age, the malnourished group exhibits greater early inhibition of the PPI using the PSA measure at IPIs between 20 and 30 ms regardless of vigilance state, while at 30 days of age, the malnourished group exhibits greater facilitation at IPIs between 50 and 70 ms during QW and SWS, but not during REM sleep. In the control adult (PND90) and juvenile (PND30) animal, PSA(1) values are significantly higher during SWS than in QW or REM sleep. However, for the younger malnourished animals (PND15 and PND30), PSA(1) values were found to be significantly greater during REM sleep rather than SWS. Therefore, as the animal matures, there appears to be a shift in vigilance state dependent synaptic transmission through the hippocampal trisynaptic circuit from REM sleep to SWS in both control and malnourished animals, with the change occurring later in malnourished animals when compared to control ones. Furthermore, our findings suggests that prenatal protein malnutrition significantly alters modulation of dentate granule cell excitability (i.e., PPI values using the PSA measure) during the earlier stages of development but not in adulthood.     

Dentate granule cell modulation in freely moving rats: vigilance state effects

Dentate granule cell population responses to paired-pulse stimulation applied to the perforant pathway across a range of interpulse intervals (IPIs) were examined during different vigilance states-quiet waking (QW), slow-wave sleep (SWS), and rapid-eye movement (REM) sleep-in freely moving rats at 15, 30 and 90 days of age. Using these evoked field potentials, the paired-pulse index (PPI), a measure of the type and degree of modulation of dentate granule cell excitability, was computed and shown to be altered as a function of age. Animals, 15 days old, showed significantly lower levels of early inhibition (20-40 ms IPIs), i.e., greater PPI values, during all three vigilance states when compared to both the 30- and 90-day old animals. Adult, i.e, 90-day old animals, on the other hand, showed significantly greater levels of late inhibition (300-1000 ms IPIs), i.e., lower PPI values, than the younger animals (15- and 30-day old) during QW and SWS. These results indicate that as the dentate field of the hippocampal formation matures there are significant alterations in the modulation of dentate granule cell activity.     

Adverse outcome of infants with metastatic neuroblastoma, MYCN amplification and/or bone lesions: results of the French society of pediatric oncology

To assess the relevance of MYCN amplification and bone lesions in stage 4 neuroblastoma (NB) in infants aged <1 year, 51 infants with stage 4 NB were enrolled. Three groups of patients were defined according to the type of metastases and the resectability of the primary tumour. Group I comprised 21 infants with radiologically detectable bone lesions, Group II 22 patients with an unresectable primary tumour and Group III eight patients with only metaiodobenzylguanidine (MIBG) skeletal uptake. MYCN oncogene content was assayed in 47/51 tumours and found to be amplified in 17 (37%). The 5-year event-free survival (EFS) rate of these 51 infants was 64.1% (+/- 7.1%). In a univariate analysis, bone lesions, MYCN amplification, urinary vanillylmandelic/homovanillic acid ratio and serum ferritin levels adversely influenced outcome. In the multivariate analysis, radiologically detectable bone lesions were the most powerful unfavourable prognostic indicator: the EFS rate was 27.2% for these infants compared to 90% for infants without bone lesions (P<0.0001). Our data emphasize the poor prognosis of infants affected by stage 4 NB with bone lesions, especially when associated with MYCN amplification. Given the poor results in this group whatever the treatment, new therapeutic approaches need to be investigated in the future.     

Nutri-Score and NutrInform Battery: Effects on Performance and Preference in Italian Consumers

In May 2020, the European Commission announced a proposal for a mandatory front-of-pack label (FoPL) for all European Union (EU) countries. Indeed, FoPLs have been recognized by several public institutions as a cost-effective measure to guide consumers toward nutritionally favorable food products. The aim of this study was to compare the performance and consumer preference of two FoPLs currently proposed or implemented in EU countries, the interpretive format Nutri-Score and the non-interpretive format NutrInform Battery, among Italian consumers. The experimental study was conducted in 2021 on a representative sample of 1064 Italian adults (mean age = 46.5 ± 14.1 years; 48% men). Participants were randomized to either Nutri-Score or NutrInform and had to fill out an online questionnaire testing their objective understanding of the FoPL on three food categories (breakfast products, breakfast cereals and added fats) as well as purchase intention, subjective understanding and perception. Multivariable logistic regressions and t-tests were used to analyze the answers. In terms of the capacity of participants to identify the most nutritionally favorable products, Nutri-Score outperformed NutrInform in all food categories, with the highest odds ratio being observed for added fats (OR = 21.7 [15.3–31.1], p < 0.0001). Overall, with Nutri-Score, Italian participants were more likely to intend to purchase nutritionally favorable products than with NutrInform (OR = 5.29 [4.02–6.97], p < 0.0001). Focusing on olive oil, participants of the Nutri-Score group had higher purchase intention of olive oil compared to those in the NutrInform group (OR = 1.92 [1.42–2.60], p < 0.0001) after manipulating the label. The interpretive format Nutri-Score appears to be a more efficient tool than NutrInform for orienting Italian consumers towards more nutritionally favorable food choices.