The retrosplenial cortex and object recency memory in the rat.

It has been proposed that the retrosplenial cortex forms part of a 'where/when' information network. The present study focussed on the related issue of whether retrosplenial cortex also contributes to 'what/when' information, by examining object recency memory. In Experiment 1, rats with retrosplenial lesions were found to be impaired at distinguishing the temporal order of objects presented in a continuous series ('Within-Block' condition). The same lesioned rats could, however, distinguish between objects that had been previously presented in one of two discrete blocks ('Between-Block' condition). Experiment 2 used intact rats to map the expression of the immediate-early gene c-fos in retrosplenial cortex following performance of a between-block, recency discrimination. Recency performance correlated positively with levels of c-fos expression in both granular and dysgranular retrosplenial cortex (areas 29 and 30). Expression of c-fos in the granular retrosplenial cortex also correlated with prelimbic cortex and ventral subiculum c-fos activity, the latter also correlating with recency memory performance. The combined findings from both experiments reveal an involvement of the retrosplenial cortex in temporal order memory, which includes both between-block and within-block problems. The current findings also suggest that the rat retrosplenial cortex comprises one of a group of closely interlinked regions that enable recency memory, including the hippocampal formation, medial diencephalon and medial frontal cortex. In view of the well-established importance of the retrosplenial cortex for spatial learning, the findings support the notion that, with its frontal and hippocampal connections, retrosplenial cortex has a key role for both what/when and where/when information.

Detecting and discriminating novel objects: The impact of perirhinal cortex disconnection on hippocampal activity patterns.

Perirhinal cortex provides object-based information and novelty/familiarity information for the hippocampus. The necessity of these inputs was tested by comparing hippocampal c-fos expression in rats with or without perirhinal lesions. These rats either discriminated novel from familiar objects (Novel-Familiar) or explored pairs of novel objects (Novel-Novel). Despite impairing Novel-Familiar discriminations, the perirhinal lesions did not affect novelty detection, as measured by overall object exploration levels (Novel-Novel condition). The perirhinal lesions also largely spared a characteristic network of linked c-fos expression associated with novel stimuli (entorhinal cortex→CA3→distal CA1→proximal subiculum). The findings show: I) that perirhinal lesions preserve behavioral sensitivity to novelty, whilst still impairing the spontaneous ability to discriminate novel from familiar objects, II) that the distinctive patterns of hippocampal c-fos activity promoted by novel stimuli do not require perirhinal inputs, III) that entorhinal Fos counts (layers II and III) increase for novelty discriminations, IV) that hippocampal c-fos networks reflect proximal-distal connectivity differences, and V) that discriminating novelty creates different pathway interactions from merely detecting novelty, pointing to top-down effects that help guide object selection. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.

Perirhinal cortex lesions impair tests of object recognition memory but spare novelty detection.

The present study examined why perirhinal cortex lesions in rats impair the spontaneous ability to select novel objects in preference to familiar objects, when both classes of object are presented simultaneously. The study began by repeating this standard finding, using a test of delayed object recognition memory. As expected, the perirhinal cortex lesions reduced the difference in exploration times for novel vs. familiar stimuli. In contrast, the same rats with perirhinal cortex lesions appeared to perform normally when the preferential exploration of novel vs. familiar objects was tested sequentially, i.e. when each trial consisted of only novel or only familiar objects. In addition, there was no indication that the perirhinal cortex lesions reduced total levels of object exploration for novel objects, as would be predicted if the lesions caused novel stimuli to appear familiar. Together, the results show that, in the absence of perirhinal cortex tissue, rats still receive signals of object novelty, although they may fail to link that information to the appropriate object. Consequently, these rats are impaired in discriminating the source of object novelty signals, leading to deficits on simultaneous choice tests of recognition.

Control by the brain of vitamin A homeostasis.

Vitamin A is a micronutrient essential for vertebrate animals maintained in homeostatic balance in the body; however, little is known about the control of this balance. This study investigated whether the hypothalamus, a key integrative brain region, regulates vitamin A levels in the liver and circulation. Vitamin A in the form of retinol or retinoic acid was stereotactically injected into the 3rd ventricle of the rat brain. Alternatively, retinoids in the mouse hypothalamus were altered through retinol-binding protein 4 (Rbp4) gene knockdown. This led to rapid change in the liver proteins controlling vitamin A homeostasis as well as vitamin A itself in liver and the circulation. Prolonged disruption of Rbp4 in the region of the arcuate nucleus of the mouse hypothalamus altered retinol levels in the liver. This supports the concept that the brain may sense retinoids and influence whole-body vitamin A homeostasis with a possible "vitaminostatic" role.

The effect of food packaging elements on children's food choices and intake: A systematic review.

Little can be added about the worldwide concern over the exponential increase in obesity and child overweight problems. Much of the unhealthy eating habits occur at the time of food choice. The enormous influence of marketing strategies in general, and packaging in particular, has been highlighted here. In this respect, public policies that tend to direct choices toward healthier options have been developed. However, the usefulness of such policies will depend on evidence of how different packaging elements can influence children. This systematic review (SR) aims to compile the knowledge available to date on the influence of packaging on food choices and eating behaviours in children. Methodologically, the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines have been followed to select papers. We also assessed the risk of bias in the studies analysed using the Newcastle-Ottawa Quality Assessment Scale (NOS). The initial search strategy found 2,627 articles, although only 20 of them met the eligibility criteria. Data from the studies were extracted, categorised, and analysed. The results indicate that most of the packaging elements have some effect on children's food choices or food intake. The use of Cartoon is the element with the most consistent evidence of influence. Despite the number of studies and public initiatives developed to promote this informative and persuasive element, less consistency has been found regarding the effect of Nutrition Labelling. Therefore, the results found should be considered by both governments and organisations when promoting public policies that work for the wellbeing of children.

Eating Behaviour Changes during the COVID-19 Pandemic: A Systematic Review of Longitudinal Studies.

Eating behaviour is a complex construct that is liable to be modified by external factors. Due to the outbreak of coronavirus disease 2019 (COVID-19), many restrictive measures were carried out with the aim of reducing the impact of this disease. As a result, lifestyles were disrupted, which could affect eating behaviours. The aim of this systematic review of longitudinal studies was to assess changes in eating behaviour during the COVID-19 pandemic by establishing a comparison of eating behaviours before and after the outbreak of the pandemic. This study followed the PRISMA guidelines (PROSPERO: CRD42020203246), whereas to assess the quality of the studies, the Newcastle-Ottawa Quality Assessment Scale (NOS) was applied. Out of a set of 826 studies, 23 were included in this systematic review. The main findings provided information about a shift towards modified eating behaviours, characterized by an increased snack frequency and a preference for sweets and ultra-processed food rather than fruits, vegetables, and fresh food. Additionally, an increased alcohol consumption was found among different countries. Consequently, adherence to healthy diets decreased. These findings are relevant to future policies and strategies to assess nutrition in cases of alarming situations such as the current COVID-19 pandemic.

Medial temporal pathways for contextual learning: Network c-fos mapping in rats with or without perirhinal cortex lesions.

BACKGROUND: In the rat brain, context information is thought to engage network interactions between the postrhinal cortex, medial entorhinal cortex, and the hippocampus. In contrast, object information is thought to be more reliant on perirhinal cortex and lateral entorhinal cortex interactions with the hippocampus. METHOD: The 'context network' was explored by mapping expression of the immediate-early gene, c-fos, after exposure to a new spatial environment. RESULTS: Structural equation modelling of Fos counts produced networks of good fit that closely matched prior predictions based on anatomically-grounded functional models. These same models did not, however, fit the Fos data from home-cage controls nor did they fit the corresponding data from a previous study exploring object recognition. These additional analyses highlight the specificity of the context network. The home-cage controls, meanwhile, showed raised levels of inter-area Fos correlations between the many sites examined, i.e., their changes in Fos levels lacked anatomical specificity. Two additional groups of rats received perirhinal cortex lesions. While the loss of perirhinal cortex reduced lateral entorhinal c-fos activity, it did not affect mean levels of hippocampal c-fos expression. Similarly, overall c-fos expression in the prelimbic cortex, retrosplenial cortex and nucleus reuniens of the thalamus appeared unaffected by the perirhinal cortex lesions. CONCLUSION: The perirhinal cortex lesions disrupted network interactions involving the medial entorhinal cortex and the hippocampus, highlighting ways in which perirhinal cortex might affect specific aspects of context learning.

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation.

Obesity is primarily due to food intake in excess of the body's energetic requirements, intake that is not only associated with hunger but also the incentive value of food. The 5-hydroxytryptamine 2C receptor (5-HT2CR) is a target for the treatment of human obesity. Mechanistically, 5-HT2CRs are positioned to influence both homeostatic feeding circuits within the hypothalamus and reward circuits within the ventral tegmental area (VTA). Here we investigated the role of 5-HT2CRs in incentive motivation using a mathematical model of progressive ratio (PR) responding in mice. We found that the 5-HT2CR agonist lorcaserin significantly reduced both ad libitum chow intake and PR responding for chocolate pellets and increased c-fos expression in VTA 5-HT2CR expressing γ-aminobutyric acid (GABA) neurons, but not 5-HT2CR expressing dopamine (DA) neurons. We next adopted a chemogenetic approach using a 5-HT2CRCRE line to clarify the function of subset of 5-HT2C receptor expressing VTA neurons in the modulation of appetite and food-motivated behavior. Activation of VTA 5-HT2C receptor expressing neurons significantly reduced ad libitum chow intake, operant responding for chocolate pellets, and the incentive value of food. In contrast, chemogenetic inhibition of VTA 5-HT2C receptor expressing neurons had no effect on the feeding behavior. These results indicate that activation of the subpopulation of 5-HT2CR neurons within the VTA is sufficient to significantly reduce homeostatic feeding and effort-based intake of palatable food, and that this subset has an inhibitory role in motivational processes. These findings are relevant to the treatment of obesity.

Perirhinal cortex lesions that impair object recognition memory spare landmark discriminations.

Rats with lesions in the perirhinal cortex and their control group learnt to discriminate between mirror-imaged visual landmarks to find a submerged platform in a watermaze. Rats initially learnt this discrimination passively, in that they were repeatedly placed on the platform in one corner of a square watermaze with walls of different appearance, prior to swimming to that same location for the first time in a subsequent probe trial. Perirhinal cortex lesions spared this passively learnt ability, despite the common visual elements shared by the guiding landmarks. These results challenge models of perirhinal function that emphasise its role in solving discriminations between stimuli with ambiguous or overlapping features, while underlining how this cortical region is often not required for spatial processes that involve the hippocampus.

Perirhinal cortex lesions in rats: Novelty detection and sensitivity to interference.

Rats with perirhinal cortex lesions received multiple object recognition trials within a continuous session to examine whether they show false memories. Experiment 1 focused on exploration patterns during the first object recognition test postsurgery, in which each trial contained 1 novel and 1 familiar object. The perirhinal cortex lesions reduced time spent exploring novel objects, but did not affect overall time spent exploring the test objects (novel plus familiar). Replications with subsequent cohorts of rats (Experiments 2, 3, 4.1) repeated this pattern of results. When all recognition memory data were combined (Experiments 1-4), giving totals of 44 perirhinal lesion rats and 40 surgical sham controls, the perirhinal cortex lesions caused a marginal reduction in total exploration time. That decrease in time with novel objects was often compensated by increased exploration of familiar objects. Experiment 4 also assessed the impact of proactive interference on recognition memory. Evidence emerged that prior object experience could additionally impair recognition performance in rats with perirhinal cortex lesions. Experiment 5 examined exploration levels when rats were just given pairs of novel objects to explore. Despite their perirhinal cortex lesions, exploration levels were comparable with those of control rats. While the results of Experiment 4 support the notion that perirhinal lesions can increase sensitivity to proactive interference, the overall findings question whether rats lacking a perirhinal cortex typically behave as if novel objects are familiar, that is, show false recognition. Rather, the rats retain a signal of novelty but struggle to discriminate the identity of that signal.

Contrasting networks for recognition memory and recency memory revealed by immediate-early gene imaging in the rat.

The expression of the immediate-early gene c-fos was used to compare networks of activity associated with recency memory (temporal order memory) and recognition memory. In Experiment 1, rats were first familiarized with sets of objects and then given pairs of different, familiar objects to explore. For the recency test group, each object in a pair was separated by 110 min in the time between their previous presentations. For the recency control test, each object in a pair was separated by less than a 1 min between their prior presentations. Temporal discrimination of the objects correlated with c-fos activity in the recency test group in several sites, including area Te2, the perirhinal cortex, lateral entorhinal cortex, as well as the dentate gyrus, hippocampal fields CA3 and CA1. For both the test and control conditions, network models were derived using structural equation modeling. The recency test model emphasized serial connections from the perirhinal cortex to lateral entorhinal cortex and then to the CA1 subfield. The recency control condition involved more parallel pathways, but again highlighted CA1 within the hippocampus. Both models contrasted with those derived from tests of object recognition (Experiment 2), because stimulus novelty was associated with pathways from the perirhinal cortex to lateral entorhinal cortex that then involved both the dentate gyrus (and CA3) and CA1 in parallel. The present findings implicate CA1 for the processing of familiar stimuli, including recency discriminations, while the dentate gyrus and CA3 pathways are recruited when the perirhinal cortex signals novel stimuli.

The neural basis of nonvisual object recognition memory in the rat.

Research into the neural basis of recognition memory has traditionally focused on the remembrance of visual stimuli. The present study examined the neural basis of object recognition memory in the dark, with a view to determining the extent to which it shares common pathways with visual-based object recognition. Experiment 1 assessed the expression of the immediate-early gene c-fos in rats that discriminated novel from familiar objects in the dark (Group Novel). Comparisons made with a control group that explored only familiar objects (Group Familiar) showed that Group Novel had higher c-fos activity in the rostral perirhinal cortex and the lateral entorhinal cortex. Outside the temporal region, Group Novel showed relatively increased c-fos activity in the anterior medial thalamic nucleus and the anterior cingulate cortex. Both the hippocampal CA fields and the granular retrosplenial cortex showed borderline increases in c-fos activity with object novelty. The hippocampal findings prompted Experiment 2. Here, rats with hippocampal lesions were tested in the dark for object recognition memory at different retention delays. Across two replications, no evidence was found that hippocampal lesions impair nonvisual object recognition. The results indicate that in the dark, as in the light, interrelated parahippocampal sites are activated when rats explore novel stimuli. These findings reveal a network of linked c-fos activations that share superficial features with those associated with visual recognition but differ in the fine details; for example, in the locus of the perirhinal cortex activation. While there may also be a relative increase in c-fos activation in the extended-hippocampal system to object recognition in the dark, there was no evidence that this recognition memory problem required an intact hippocampus.