Hippocampal and prefrontal contributions to memory retrieval: Examination of immediate early gene,NMDA receptor and environmental interactions

Animals can use a range of strategies to recall important locations. These include simple stimulus–response strategies and more complex spatial (place) strategies, which are thought to have distinct neural substrates. The hippocampus—and NMDA receptor activation therein—is considered to be crucial for spatial, but not response strategies. The medial prefrontal cortex has also been implicated in memory retrieval; however, evidence concerning its specific role is equivocal. Both hippocampal and prefrontal regions have been associated with flexible behavioural responding (e.g. when task demands change). Here, we investigated the use of spatial and non‐spatial strategies in the Morris water maze and their associated brain areas in rats using immediate early gene (IEG) imaging of Zif268 and c‐Fos. Specifically, we charted the involvement of hippocampal and prefrontal subregions during retrieval of spatial and non‐spatial memories. Behavioural flexibility was also examined using intact and partial cue configurations during recall. Results indicated that regions of both the hippocampus (area CA3) and prefrontal cortex (anterior cingulate cortex) were preferentially engaged in spatial memory recall compared to response learning. In addition, both spatial and non‐spatial memories were dependent on NMDA receptor activation. MK801 impaired recall performance across all groups and reduced IEG activation across hippocampal and prefrontal regions. Finally, IEG results revealed divergent patterns of Zif268 and c‐Fos activity and support the suggestion that Zif268 plays a functional role in the recall of long‐term memories.     

Sleep,brain development,and autism spectrum disorders: Insights from animal models

Sleep is an evolutionarily conserved and powerful drive, although its complete functions are still unknown. One possible function of sleep is that it promotes brain development. The amount of sleep is greatest during ages when the brain is rapidly developing, and sleep has been shown to influence critical period plasticity. This supports a role for sleep in brain development and suggests that abnormal sleep in early life may lead to abnormal development. Autism spectrum disorder (ASD) is the most prevalent neurodevelopmental disorder in the United States. It is estimated that insomnia affects 44%–86% of the ASD population, predicting the severity of ASD core symptoms and associated behavioral problems. Sleep problems impact the quality of life of both ASD individuals and their caregivers, thus it is important to understand why they are so prevalent. In this review, we explore the role of sleep in early life as a causal factor in ASD. First, we review fundamental steps in mammalian sleep ontogeny and regulation and how sleep influences brain development. Next, we summarize current knowledge gained from studying sleep in animal models of ASD. Ultimately, our goal is to highlight the importance of understanding the role of sleep in brain development and the use of animal models to provide mechanistic insight into the origin of sleep problems in ASD.     

戊型肝炎病毒与鼠形动物的关系

戊型肝炎病毒所导致的戊型病毒性肝炎（戊型肝炎）全球流行严重,是重要的公共卫生问题之一。戊型肝炎病毒是一种动物源性单股正链RNA病毒,属于戊型肝炎病毒科,该科分为正戊肝病毒属和鱼戊肝病毒属。正戊肝病毒属包括A物种、B物种、C物种、D 物种共4种;鱼戊肝病毒属仅有A物种。先前的研究认为戊型肝炎病毒不会跨物种传播,但最近发现有戊肝病毒通过鼠形动物传染给人的情况,而鼠形动物在病毒传播及流行过程中扮演的角色和发挥的作用尚不清楚。本文综述了A物种正戊肝病毒和C物种正戊肝病毒与鼠形动物的关系,并对香港鼠传人戊肝事件进行思考,推测此次传播可能存在病毒变异,使病毒的传染力增强,获得了跨物种传播的能力;C物种正戊肝病毒所致的戊肝可能成为一种新的人兽共患病。建议对鼠形动物感染戊肝病毒的类型、感染率及空间分布特征进行深入研究,前移戊肝防控关口,为科学精准防控戊型肝炎提供新的思路。同时,鼠形动物是动物源性疾病病原体的重要宿主,明确该种群携带戊肝病毒的情况,有助于科学评估戊肝病毒通过鼠形动物传染给人的潜在风险。     

Development of behavioral responses to thermal challenges

Body temperature regulation involves the development of responses to cold and warm challenges. Matching our understanding of the development of body temperature regulation to warm challenges with that of cold challenges will enhance our understanding of the ontogeny of thermoregulation and reveal different adaptive specializations. Warm and cold thermoregulation are important processes, and they include direct thermal effects on offspring, as well as indirect effects on them, such as those imposed by thermally associated alterations of maternal behavior. The present paper is a selective review of the existing literature and a report of some new empirical data, aimed at processes of mammalian development, especially those affecting behavior. We briefly discuss the development of body temperature regulation in rats and mice, and thermal aspects of maternal behavior with emphasis on responses to high temperatures. The new data extend previous analyses of individual and group responses in developing rodents to warm and cool ambient temperatures. This literature not only reveals a variety of adaptive specializations during development, but it points to the earlier appearance in young mammals of abilities to combat heat loss, relative to protections from hyperthermia. These relative developmental delays in compensatory defenses to heating appear to render young mammals especially vulnerable to environmental warming. We describe cascading consequences of warming—effects that illustrate interactions across levels of physiological, neural, and behavioral development.     

The Stapedial Artery in the Mongolian Gerbil (Meriones unguiculatus)

The persistent stapedial artery is a component of the main arterial roads of the head in some animal groups (Fr?ckowiak: Roczn Akad Roln Poznań 336 (2003) 1–81). This type of vascularization occurs in the Mongolian gerbil, among others. The stapedial artery is common in a variety of forms in rodents. It has been described, for example, in Sciuridae, Muridae, Heteromyidae, Geomyidae, Splacidae, Cricetidae, Arvicolinae, and in genus Jaculus (Cox and Hautier: Evolution of the Rodents: Advances in phylogeny, Functional Morphology and Development, 2015). The aim of this study was the analysis of morphology, and of course, of the stapedial artery in this species. Investigations were performed on 10 animals of both sexes, weighing 50–60 g. After lethal anesthesia, the vascular system of every animal was filled with colored latex. After latex coagulation and decalcification of skull bones, fixed tissues were delicately prepared, and the head vascular system was exposed. The stapedial artery separates from the internal carotid artery, runs toward the auditory bulb and passes through the stapes. After the branching of the medial meningeal artery, the stapedial artery runs rostrally, forming its infraorbital branch. This branch, in the further course, gives the branch forming the short trunk of the ophthalmic artery, which supplies orbital structures (muscles, lacrimal gland, Harderian gland, and eyeball). The performed investigations revealed that the maintained infraorbital branch of the stapedial artery is the only source of arterial supply of the orbit in this species. Anat Rec, 301:1131–1137, 2018. © 2018 Wiley Periodicals, Inc.     

Murine Typhus,Reunion, France, 2011–2013

Murine typhus case was initially identified in Reunion, France, in 2012 in a tourist. Our investigation confirmed 8 autochthonous cases that occurred during January 2011–January 2013 in Reunion. Murine typhus should be considered in local patients and in travelers returning from Reunion who have fevers of unknown origin.     

Golgi phosphoprotein 4 (GPP130) is a sensitive and selective cellular target of manganese exposure

Chronic elevated exposure to manganese (Mn) is associated with neurocognitive and fine motor deficits in children. However, relatively little is understood about cellular responses to Mn spanning the transition between physiologic to toxic levels of exposure. Here, we investigated the specificity, sensitivity, and time course of the Golgi Phosphoprotein 4 (GPP130) response to Mn exposure in AF5 GABAergic neuronal cells, and we determined the extent to which GPP130 degradation occurs in brain cells in vivo in rats subchronically exposed to Mn. Our results show that GPP130 degradation in AF5 cells was specific to Mn, and did not occur following exposure to cobalt, copper, iron, nickel, or zinc. GPP130 degradation occurred without measurable increases in intracellular Mn levels and at Mn exposures as low as 0.54 µM. GPP130 protein was detectable by immunofluorescence in only ～15–30% of cells in striatal and cortical rat brain slices, and Mn‐exposed animals exhibited a significant reduction in both the number of GPP130‐positive cells, and the overall levels of GPP130 protein, demonstrating the in vivo relevance of this Mn‐specific response within the primary target organ of Mn toxicity. These results provide insight into specific mechanism(s) of cellular Mn regulation and toxicity within the brain, including the selective susceptibility of cells to Mn cytotoxicity. Synapse 67:205–215, 2013. © 2012 Wiley Periodicals, Inc.     

Public Health Implications of Changing Rodent Importation Patterns – United States, 1999–2013

The United States imports a large volume of live wild and domestic animal species; these animals pose a demonstrated risk for introduction of zoonotic diseases. Rodents are imported for multiple purposes, including scientific research, zoo exhibits and the pet trade. Current U.S. public health regulatory restrictions specific to rodent importation pertain only to those of African origin. To understand the impacts of these regulations and the potential public health risks of international rodent trade to the United States, we evaluated live rodent import records during 1999–2013 by shipment volume and geographic origin, source (e.g. wild‐caught versus captive‐ or commercially bred), intended purpose and rodent taxonomy. Live rodent imports increased from 2737 animals during 1999 to 173 761 animals during 2013. Increases in both the number and size of shipments contributed to this trend. The proportion of wild‐captured imports declined from 75% during 1999 to <1% during 2013. Nearly all shipments during these years were imported for commercial purposes. Imports from Europe and other countries in North America experienced notable increases in volume. Gerbils and hamsters arriving from Europe and chinchillas, guinea pigs and hamsters arriving from other countries in North America were predominant taxa underlying this trend. After 2003, African‐origin imports became sporadic events under the federal permit process. These patterns suggest development of large‐scale captive rodent breeding markets abroad for commercial sale in the United States. While the shift from wild‐captured imports alleviates many conservation concerns and risks for novel disease emergence, such consolidated sourcing might elevate exposure risks for zoonotic diseases associated with high‐density rodent breeding (e.g. lymphocytic choriomeningitis or salmonellosis). A responsive border health system must periodically re‐evaluate importation regulations in conjunction with key stakeholders to ensure a balance between the economic benefits of rodent trade against the potential public health risks.     

Reliability and spatial specificity of rat brain sensorimotor functional connectivity networks are superior under sedation compared with general anesthesia

Functional connectivity networks derived from resting‐state functional MRI (rsfMRI) have received increasing interest to further our understanding of brain function. The anesthesia in rodent models may influence the interpretation and comparison of results from functional connectivity MRI (fcMRI). More research is required on this aspect. In this study, we investigated rat brain connectivity networks under 1.5% isoflurane anesthesia in comparison with medetomidine sedation. rsfMRI data were acquired under both anesthesia conditions within one imaging session. Male Wistar rats (n = 17) were scanned at 11.7 T with focus on the sensorimotor system. The data underwent a per‐subject independent component analysis (ICA), after which individual components were grouped using hierarchical clustering. Consistent and reliable networks were identified under medetomidine in sensorimotor cortex (three networks) and striatum (two networks). The incidence of these networks was drastically reduced under isoflurane. Seed correlation analysis confirmed these results and revealed globally elevated correlations with low topical specificity under isoflurane, stemming from low‐frequency global signal fluctuations. Global signal removal thus enhanced slightly regional specificity under isoflurane and showed anti‐correlations of cortico‐striatal connections in both anesthesia regimes. Functional connectivity networks are thus reliably detected in medetomidine‐sedated animals on an individual basis using ICA. Their occurrence, however, is heavily compromised under isoflurane as a result of global signal fluctuations potentially stemming from burst‐suppression‐like neural activity. Anesthesia and pharmacologically induced modulations may provide insight into network mechanisms in the future. As an agent for fcMRI in brain disease studies, light sedation using medetomidine preserves connectivity networks in a greater level of detail, and may therefore be considered superior to standard isoflurane anesthesia. Copyright © 2013 John Wiley & Sons, Ltd.     

Automated transfer and injection of hyperpolarized molecules with polarization measurement prior to in vivo NMR

Hyperpolarized magnetic resonance via dissolution dynamic nuclear polarization necessitates the transfer of the hyperpolarized molecules from the polarizer to the imager prior to in vivo measurements. This process leads to unavoidable losses in nuclear polarization, which are difficult to evaluate once the solution has been injected into an animal. We propose a method to measure the polarization of the hyperpolarized molecules inside the imager bore, 3 s following dissolution, at the time of the injection, using a precise quantification of the infusate concentration. This in situ quantification allows for distinguishing between signal modulations related to variations in the nuclear polarization at the time of the injection and signal modulations related to physiological processes such as tissue perfusion. In addition, our method includes a radical scavenging process that leads to a minor reduction in sample concentration and takes place within a couple of seconds following the dissolution in order to minimize the losses due to the presence of paramagnetic polarizing agent in the infusate. We showed that proton exchange between vitamin C, the scavenging molecule and the deuterated solvent shortens the long carboxyl ¹³C longitudinal relaxation time in [1‐¹³C]acetate. This additional source of dipolar relaxation can be avoided by using deuterated ascorbate. Overall, the method allows for a substantial gain in polarization and also leads to an extension of the time window available for in vivo measurements. Copyright © 2013 John Wiley & Sons, Ltd.