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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

animal model --- autoimmunity --- autophagy --- genetics --- human disease --- translational research --- therapy

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Schizophrenia is a multi-factorial disease characterized by a high heritability and environmental risk factors (e.g. stress and cannabis use). In recent years, an increasing number of researchers worldwide have started investigating the ‘two-hit hypothesis’ of schizophrenia predicting that genetic and environmental risk factors interactively cause the development of the disorder. This work is starting to produce valuable new animal models and reveal novel insights into the pathophysiology of schizophrenia. Eventually, it might help advance studies of the molecular pathways involved in this mental disorder and propose more specific molecular medicine. However, the complexity of this multi-factorial line of research has also caused difficulties in data interpretation and comparison. Our research topic is intended to cover past and current directions in research dedicated to the understanding and measurement of gene-environment interactions (GxE) in schizophrenia, the neurobiological and behavioural consequences of such interactions as well as the challenges and limitations one encounters when working on complex aetiological systems.

Schizophrenia. --- Genotype-environment interaction. --- environment --- gene --- GxE --- Interaction --- two hit hypothesis --- Schizophrenia --- animal model

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This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact

precise genome editing --- CRISPR --- HDR efficiency --- biallelic HDR targeting --- off-target effect --- animal model --- base editing

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Habituation describes the progressive decrease of the amplitude or frequency of a motor response to repeated sensory stimulation that is not caused by sensory receptor adaptation or motor fatigue. Habituation can occur in different time scales: habituation within a testing session has been termed short-term habituation, whereas habituation across testing sessions has been termed long-term habituation. Generally, the more spaced the stimuli for inducing habituation are presented (i.e. the slower habituation is induced), the longer it seems to take to recover the behavioural response to its initial magnitude. Habituation is opposed by behavioural sensitization, which is thought to be an independent mechanism that leads to an increased behavioural response, especially if the sensory stimulus is annoying or aversive. Habituation provides an important mechanism for filtering sensory information, as it allows filtering out irrelevant stimuli and thereby focussing on important stimuli, a prerequisite for many cognitive tasks. The importance is demonstrated in mental disorders that are associated with disruptions in habituation, e.g. schizophrenia and autism spectrum disorders. The inability to filter out irrelevant information in patients with these disorders strongly correlates with disruptions in higher cognitive functions, such as in different types of memory and attention. Habituation is also considered to be the most basic form of non-associative implicit learning, and it can be observed throughout the animal kingdom. Based on the importance of habituation for cognitive function and therefore for the survival of an animal, it is assumed that habituation mechanisms are highly conserved across species. On the other hand, there is emerging evidence for a multitude of homo- and heterosynaptic mechanisms underlying habituation, depending on the modality of sensory stimulation, the level of sensory information processing where habituation occurs, and the temporal composition of sensory stimulation. Eric Kandel used the sea hare Aplysia in order to study habituation mechanisms of the gill withdrawal reflex; however, the molecular mechanisms remain largely elusive to date. A multitude of different organisms, behaviours, and experimental approaches have been used since in order to study habituation, but still surprisingly little is known about the underlying mechanisms. New insights also come from an unexpected side: in the recent past, groups that have been studying molecular mechanisms underlying short- and long-term synaptic plasticity phenomenons in different parts of the rodent brain are starting to link these plasticity processes to behavioural habituation. The scope of this Frontier Research Topic is to give an overview over the concept of habituation, different animal and behavioural models used for studying habituation mechanisms, as well as the different synaptic and molecular processes suggested to play a role in behavioural habituation through Original Research Articles, Methods, Hypothesis & Theory Articles, and Reviews.

Learning and memory. --- Habituation. --- Sensorimotor gating --- startle --- learning and memory --- habituation --- spike adaptation --- synaptic mechanism --- animal model

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Despite significant progress in the global fight against malaria, this parasitic infection is still responsible for nearly 300 million clinical cases and more than half a million deaths each year, predominantly in African children less than 5 years of age. The infection starts when mosquitoes transmit small numbers of parasites into the skin. From here, the parasites travel with the bloodstream to the liver where they undergo an initial round of replication and maturation to the next developmental stage that infects red blood cells. A vaccine capable of blocking the clinically silent liver phase of the Plasmodium life cycle would prevent the subsequent symptomatic phase of this tropical disease, including its frequently fatal manifestations such as severe anemia, acute lung injury, and cerebral malaria. Parasitologists, immunologists, and vaccinologists have come to appreciate the complexity of the adaptive immune response against the liver stages of this deadly parasite. Lymphocytes play a central role in the elimination of Plasmodium infected hepatocytes, both in humans and animal models, but our understanding of the exact cellular interactions and molecular effector mechanisms that lead to parasite killing within the complex hepatic microenvironment of an immune host is still rudimentary. Nevertheless, recent collaborative efforts have led to promising vaccine approaches based on liver stages that have conferred sterile immunity in humans – the University of Oxford's Ad prime / MVA boost vaccine, the Naval Medical Research Center’s DNA prime / Ad boost vaccine, Sanaria, Inc.'s radiation-attenuated whole sporozoite vaccine, and Radboud University Nijmegen Medical Centre’s chemoprophylaxis with sporozoites vaccine. The aim of this Research Topic is to bring together researchers with expertise in malariology, immunology, hepatology, antigen discovery and vaccine development to provide a better understanding of the basic biology of Plasmodium in the liver and the host’s innate and adaptive immune responses. Understanding the conditions required to generate complete protection in a vaccinated individual will bring us closer to our ultimate goal, namely to develop a safe, scalable, and affordable malaria vaccine capable of inducing sustained high-level protective immunity in the large proportion of the world’s population constantly at risk of malaria.

Plasmodium falciparum. --- Malaria --- Liver --- Hepatology. --- Immunological aspects. --- Prevention. --- Research. --- Immunology. --- Parasites. --- CD8 T cell --- Plasmodium --- B cell --- antigen-presenting cell --- immune response --- Malaria vaccine --- hepatic microenvironment --- CD4 T cell --- animal model --- adjuvants