Prenatal dietary choline supplementation modulates long-term memory development in rat offspring

The development of an organism is modulated by multiple factors, with genes and diet being examples of such factors. Previous studies on preclinical models have shown that giving supplemental choline – an essential nutrient to mammals – during the embryonic period improves performance on memory tasks during adulthood. However, the effects of an early intervention on the development of cognitive functions in the immature brain have not been widely studied. In addition, it has been well established that short-term memory in rats emerges at an earlier stage (14–15 days postnatal) than long-term memory (around 30 post-natal). The aim of this work was to examine the effect of prenatal dietary choline supplementation on longterm memory development in rats. In order to assess long-term memory, we used an objectrecognition task, which evaluates the ability to recall a previously presented stimulus. Pregnant rats were fed with the diets AIN 76-A standard (1.1 g choline/Kg food) or supplemented (5 g choline/Kg food) between embryonic days (E) 12 and E18. On the first post-natal day (PN 0), male offspring of the rats fed with the supplemented and standard diet were cross-fostered to rat dams fed a standard diet during pregnancy and tested at the age of PN21-22 or PN29-31 applying 24-hour retention tests. The supplemented animals spent less time exploring the familiar object after a 24-hour retention interval, an effect that was observed in both the group tested at PN21-22 days of age and that tested at PN29-31 days. The non-supplemented rats only showed this effect in the group tested at PN29-31 days. These results suggest that prenatal supplementation with choline accelerates the development of long-term memory in rats.This work was supported by the [MINECO/FEDER, EU, Spain] under grants [PSI2015-63737-P and PGC2018-095965-B-I00] Ministerio de Economía y Competitividad and Ministerio de Ciencia, Innovación y Universidades

Intermixed Rapid Exposure to Similar Stimuli Reduces the Effective Salience of Their Distinctive Features

Intermixed exposure to two similar stimuli, e.g., AX and BX, improves subsequent discrimination between them compared to blocked exposure (the intermixed/blocked effect). Salience modulation models, developed mainly from research with nonhuman animals and exposure to widely spaced similar stimuli, explain this effect in terms of increased salience of the unique elements, A and B. Conversely, results from experiments initially conducted with humans and exposure to close spaced similar stimuli have led to the suggestion that it is the development of well-unitized representations of unique elements that leads to better discrimination, leaving the unique elements with less effective salience. The experiments carried out here aim to replicate the intermixed/blocked effect in rats using an exposure procedure with rapid succession between stimuli and to assess the effective salience of unique elements. In Experiment 1, an aversion to a new flavor, Y, was conditioned and then an external inhibition test with AY was given. In Experiment 2, an aversion to A was conditioned and its extinction was measured on unreinforced trials. In Experiment 3, an aversion to AY was conditioned and the associated aversion to Y was measured. We found after rapid intermixed preexposure a reduction in generalization from the aversive Y element to the compound AY (Experiment 1) as well as a reduction in A’s salience (Experiments 2 and 3) compared to the effects of blocked preexposure. The results are discussed in terms of the various mechanisms underlying perceptual learning, which appear to depend on the details of the task.MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” (PGC2018-095965-B-I00, PI:IB

Does drinking saccharin weaken an association of sweet with calories? Pre-exposure effects in flavor preference learning

The main aim of this experiment was to examine the claim that exposure to non-nutritive sweeteners weakens the formation of a sweet-calorie association. Three groups of food-deprived rats received training in which they drank an almond-flavored maltodextrin and saccharin solution. A final test phase assessed their preference for almond. The groups differed in preexposure prior to training. One was pre-exposed to saccharin, one to saccharin plus maltodextrin, and the third, control condition, received only water at this stage. When the rats continued under food deprivation for the test phase, the group exposed to the compound (saccharin plus maltodextrin) showed a weaker preference than the other two groups, while those pre-exposed to saccharin showed as strong a preference as the controls. When the test was conducted with the rats no longer food-deprived, only the water group showed a strong preference. These results support the proposal that rats can form both flavor-flavor and flavor-nutrient associations, expression of which will depend on motivational state. They did not find support for the suggestion that prior exposure to a non-nutritive sweetener can enhance subsequent learning about the nutritive properties of a sweet food.This work was supported by PGC2018-095965-B-I00 & PID2022- 136219NB-I00 funded by MCIN/ AEI /10.13039/501100011033/ FEDER “Una manera de hacer Europa”

Habituation as an underlying mechanism for Sensory Specific Satiety: An assessment using flavor consumption and preference in rats

This work was supported by the Ministerio de Ciencia Innovación y Universidades, Spain [MICIU/FEDER, EU, Spain] under Grant PGC2018-095965-B-I00 awarded to Isabel de Brugada and by the research Scholarship (grant number: FPU16/01767 ) awarded to Ana González. Funding for open access charge: Universidad de Granada / CBUA .Sensory specific satiety refers to a decline in the hedonic value of the sensory properties of a particular food as it is consumed. This phenomenon is characterized by a decrement in responding as a consequence of repeated exposure, is stimulus specific, and recovers after time. All these characteristics are shared with the habituation phenomenon and for this reason, habituation has been proposed as the underlying mechanism that explains this eating regulatory system. However, several studies conducted with human models have yielded mixed results. Using rats as experimental subjects, the present study tested the following three characteristics of habituation within a Sensory Specific Satiety (SSS) framework: spontaneous recovery, dishabituation and the distractor effect. Experiment 1 demonstrated the basic effect of SSS and its spontaneous recovery over time. In Experiment 2 we found that the presentation of a dishabituator after a pre-feeding procedure had no impact on the SSS effect. Finally, in Experiment 3 the presence of a distractor during a pre-feeding procedure did not alter the expression of SSS. These results challenge the idea that SSS constitutes a typical case of habituation, at least with the procedure used here.CBUAMICIUMinisterio de Ciencia Innovación y UniversidadesEuropean Commission FPU16/01767, PGC2018-095965-B-I00Universidad de GranadaEuropean Regional Development Fun

Perceptual learning in flavor preference conditioning: restricting generalization of acquired preferences between flavors

Two experiments with rats investigated perceptual learning using a conditioned preference procedure. Experiment 1 used a between-subject procedure in which rats received either intermixed preexposure (AX, BX, AX, BX…) or blocked preexposure (AX, AX…, BX, BX…) to flavor compounds before a conditioned preference was established to AX by pairing it with sucrose. During a test, rats given intermixed preexposure showed a greater preference for AX over BX than those given blocked preexposure. Experiment 2 showed that after intermixed preexposure to AX and BX, and a block of preexposure to CX, a preference established to AX was less likely to generalize to BX than to CX. These results represent the first demonstration of the impact of the schedule of preexposure on perceptual learning using a flavor preference procedure, and they parallel those previously observed using flavor aversion procedures

Perceptual learning after rapidly alternating exposure to taste compounds: Assessment with different indices of generalization

Exposure to two similar stimuli (AX and BX; e.g., two tastes) reduces the extent to which a conditioned response later established to BX generalizes to AX. This example of perceptual learning is more evident when AX and BX are exposed in an alternating manner (AX, BX, AX, BX,. . ..) than when AX and BX AQ: 4 occurs in separate blocks (e.g., AX, AX,..BX, BX,..). We examined in male rats (N = 126) the impact of rapid alternation to AX and BX on generalization of a taste aversion from BX to AX. Experiment 1 showed that such alternating presentations (with 5-min intervals between AX and BX) reduced generalization relative to blocked exposure; but only as assessed by consumption levels and not by lick cluster size (an index of hedonic reactions). Experiment 1 also showed that the nature of exposure did not affect how A influenced performance to a novel conditioned taste, Y. Experiment 2 replicated the pattern of results involving the different influences of rapidly alternating and blocked exposure on generalization from BX to AX, and showed that this effect was only evident when rats received access to water during the 5-min intervals between AX and BX. These results reinforce parallels between perceptual learning effects in rats and humans, both at empirical and theoretical levels.This research was supported by MCIN/AEI/10.13039/501100011033/FEDER “Una manera de hacer Europa” (PGC2018-095965-B-I00; PI: Isabel de Brugada) and by the BBSRC (United Kingdom; BB/T004339/1; PI: Robert C. Honey)

Utilidad de lentes de contacto como sistemas de liberación controlada de fármacos.

Un sistema ideal de administración de fármacos oculares sería el que permitiese una facilidad de fabricación, la capacidad de autoadministración del paciente, que alcanzase la zona ocular específica requerida con la concentración deseada y durante los periodos de tiempo requeridos y, por último, los mínimos efectos secundarios sistémicos que permitan la comodidad, seguridad y cumplimiento del paciente.Una manera de conseguir un sistema de administración de fármacos de estas características es mediante una formulación adecuada del fármaco, que en última instancia pretende mejorar la biodisponibilidad ocular del mismo.Los esfuerzos para mejorar la biodisponibilidad ocular se han centrado principalmente en prolongar la permanencia del fármaco en la superficie ocular. Una de las estrategias para conseguirlo consiste en el uso de agentes espesantes, polímeros mucoadhesivos y componentes gelificantes in situ, aunque en proporciones relativamente bajas para evitar una sensación pegajosa durante el parpadeo y la visión borrosa. También hablaremos de otras técnicas como la impresión molecular o el uso de nanopartículas.<br /

Providing choice increases children's vegetable intake

This work has been partially supported by the pre-doctoral fellowship of Junta de Andalucía, grant HUM-02763 (Junta de Andalucía, Spain) and PSI2011-23702; PSI2012-31641 (MINECO, Spain).One hundred and fifty children between 4 and 6 years old were studied to examine the effect of providing them with a choice of vegetables on their vegetable consumption. Offering vegetable choice was expected to increase the children’s vegetable intake due to increased personal autonomy. The option for the children to choose the vegetables to ingest was varied across three different conditions. Within the discrete choice condition (DCC), children could choose the target vegetable at the beginning of the meal; within the continued discrete choice plus variety condition (CDCP), children were exposed to a variety of vegetables (zucchini and green beans), so that they could choose the target vegetable whenever they made a bite during the whole meal. Within the no-choice condition (NCC), children were alternately exposed to only one kind of vegetable, so that no choice possibility was provided. The choice conditions (CDCP and DCC) were associated with higher vegetable intake, in comparison to the no-choice control condition (NCC). No significant differences were found between the DCC and the CDCP regarding participants’ total vegetable intake. These results demonstrate the enhancing effect of providing choice to increase vegetable intake in young children. A higher degree of personal control and consequent level of intrinsic motivation is hypothesized to underlie the effect of choice availability.Junta de Andalucía, grant HUM-02763PSI2011-23702; PSI2012-31641 (MINECO, Spain

Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy: Genotype-phenotype correlation.

AIMS Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM), there is little information about its frequency and distribution pattern according to underlying genetic substrate. We sought to describe LGE patterns according to genotype and to analyze the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS Cardiac magnetic resonance findings and LGE distribution according to genetics was performed in a cohort of 600 DCM patients followed at 20 Spanish centers. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, LVEF 36.9 ± 13.9%) conformed the final cohort. A causative genetic variant was identified in 219 (38%) patients and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20 and MYH7 (0%, 5% and 20%, respectively). Patients with variants in DMD, DSP and FLNC showed predominance of LGE subepicardial pattern (50%, 41% and 18%, respectively) whereas patients with variants in TTN, BAG3, LMNA and MYBPC3 showed unspecific LGE patterns. Genetic yield differed according to LGE pattern. Patients with subepicardial, lineal midwall, transmural, right ventricular insertion points or with combination of LGE patterns showed increased risk of MVA compared with patients without LGE. CONCLUSION LGE patterns in DCM has a specific distribution according to the affected gene. Certain LGE patterns are associated with increased risk of MVA and with increased yield of genetic testing.This study has been funded by Instituto Salud Carlos III (ISCIII) through the projects ‘PI18/0004, PI19/01283, and PI20/0320’ (co-funded by the European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro, the Hospital Universitario Vall Hebrón, the Hospital General Universitario Gregorio Marañón, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart). F.d.F. receives grant support from ISCIII (CM20/00101). R.B. receives funding from the Obra Social la Caixa Foundation. M.B. receives funding from ISCIII (PI19/01283). The CNIC is supported by the ISCIII, Ministerio de Ciencia e Innovación of the Spanish Government (MCIN), and Pro CNIC Foundation.S