BMP9 Protects Septal Neurons from Axotomy-Evoked Loss of Cholinergic Phenotype

Cholinergic projection from the septum to the hippocampus is crucial for normal cognitive function and degeneration of cells and nerve fibers within the septohippocampal pathway contributes to the pathophysiology of Alzheimer's disease. Bone morphogenetic protein (BMP) 9 is a cholinergic differentiating factor during development both in vivo and in vitro.To determine whether BMP9 could protect the adult cholinergic septohippocampal pathway from axotomy-evoked loss of the cholinergic phenotype, we performed unilateral fimbria-fornix transection in mice and treated them with a continuous intracerebroventricular infusion of BMP9 for six days. The number of choline acetyltransferase (CHAT)-positive cells was reduced by 50% in the medial septal nucleus ipsilateral to the lesion as compared to the intact, contralateral side, and BMP9 infusion prevented this loss in a dose-dependent manner. Moreover, BMP9 prevented most of the decline of hippocampal acetylcholine levels ipsilateral to the lesion, and markedly increased CHAT, choline transporter CHT, NGF receptors p75 (NGFR-p75) and TrkA (NTRK1), and NGF protein content in both the lesioned and unlesioned hippocampi. In addition, BMP9 infusion reduced bilaterally hippocampal levels of basic FGF (FGF2) protein.These data indicate that BMP9 administration can prevent lesion-evoked impairment of the cholinergic septohippocampal neurons in adult mice and, by inducing NGF, establishes a trophic environment for these cells

New Developments in Cholinergic Imaging in Alzheimer and Lewy Body Disorders

© 2020, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. Purpose of Review: This paper aims to review novel trends in cholinergic neuroimaging in Alzheimer and Lewy body parkinsonian disorders. Recent Findings: The spectrum of cholinergic imaging is expanding with the availability of spatially more precise radioligands that allow assessment of previously less recognized subcortical and cortical structures with more dense cholinergic innervation. In addition, advances in MRI techniques now allow quantitative structural or functional assessment of both the cholinergic forebrain and the pedunculopontine nucleus, which may serve as non-invasive prognostic predictors. Multimodal imaging approaches, such as PET-MRI or multiligand PET, offer new insights into the dynamic and interactive roles of the cholinergic system at both local and larger-scale neural network levels. Summary: Our understanding of the heterogeneous roles of the cholinergic system in age-related diseases is evolving. Multimodal imaging approaches that provide complimentary views of the cholinergic system will be necessary to shed light on the impact of cholinergic degeneration on regional and large-scale neural networks that underpin clinical symptom manifestation in neurodegeneration

Rethinking the extrinsic incubation period of malaria parasites

The time it takes for malaria parasites to develop within a mosquito, and become transmissible, is known as the extrinsic incubation period, or EIP. EIP is a key parameter influencing transmission intensity as it combines with mosquito mortality rate and competence to determine the number of mosquitoes that ultimately become infectious. In spite of its epidemiological significance, data on EIP are scant. Current approaches to estimate EIP are largely based on temperature-dependent models developed from data collected on parasite development within a single mosquito species in the 1930s. These models assume that the only factor affecting EIP is mean environmental temperature. Here, we review evidence to suggest that in addition to mean temperature, EIP is likely influenced by genetic diversity of the vector, diversity of the parasite, and variation in a range of biotic and abiotic factors that affect mosquito condition. We further demonstrate that the classic approach of measuring EIP as the time at which mosquitoes first become infectious likely misrepresents EIP for a mosquito population. We argue for a better understanding of EIP to improve models of transmission, refine predictions of the possible impacts of climate change, and determine the potential evolutionary responses of malaria parasites to current and future mosquito control tools

Digital game elements, user experience and learning

The primary aim of this paper is to identify and theoretically validate the relationships between core game design elements and mechanics, user motivation and engagement and consequently learning. Additionally, it tries to highlight the moderating role of player personality traits on learning outcomes and acceptance and suggest ways to incorporate them in the game design process. To that end, it outlines the role of narrative, aesthetics and core game mechanics in facilitating higher learning outcomes through intrinsic motivation and engagement. At the same time, it discusses how player goal orientation, openness to experience, conscientiousness, sensation seeking and need for cognition influence the translation of the gameplay experience into valuable learning outcomes and user acceptance of the technology

Far from success – Far from feedback acceptance? The influence of game performance on young students’ willingness to accept critical constructive feedback during play

In a learning situation, feedback is of great importance in order to help a student to correct a possible misconception. However, previous research shows that many students tend to avoid feedback regarding failures, including critical constructive feedback (CCF) that is intended to support and guide them. This is especially true for lower-achieving students, who might perceive feedback as an ego-threat, and therefore protect themselves by neglecting it. However, it has been shown that such neglect can be suppressed by using teachable agents (TA’s). Another, but less studied factor that influences feedback acceptance is the degree or extent of failure when trying to solve a task. The present study explores if and how momentary performance levels influence middle school students’ willingness to accept CCF when playing an educational game in history – with or without a TA. On the basis of teacher assessments of the students’ general skills, data logs and analyses of sequential patterns, we concluded that the willingness to accept CCF differs between students, but also between conditions and situations. One major finding is that a TA supports the students to more readily embrace CCF, even if the effect is larger for lower-achieving students. Another finding is that indications of being far from succeeding, such as low success rates or repeated trials and revisions, have a negative impact on feedback acceptance, even if a TA mitigates some of this influence. The implications of these results are discussed in relation to meta-cognitive aspects of learning and to educational software design