Showing papers in "Neuroforum in 2020"
TL;DR: The main functions of the ENS are described under physiological conditions and a few examples of its role in gut diseases are given.
Abstract: Abstract The gut’s own autonomous nervous system, the enteric nervous system (ENS), has fascinated scientists for more than 100 years. It functions, in the true sense of the word, autonomously, by performing complex tasks and controlling vital functions independently of extrinsic inputs. At the same time, the ENS is bombarded with signals from other cells in the gut wall and lumen and has to integrate all of these inputs. We describe the main functions of the ENS under physiological conditions and give a few examples of its role in gut diseases. The ENS has received increasing attention recently as scientists outside the field of Neurogastroenterology realize its important role in the pathogenesis of Parkinson’s, autism and multiple sclerosis.
9 citations
TL;DR: In this article, the authors present nine neuromythms on the topic of learning and memory, and discuss what determines their emergence and prevalence, to what extent they pose a problem for practice, and why and how both neurodidactics and neurmyths should be made an object of university instruction.
Abstract: Abstract Brain-friendly learning is a new catchphrase in school and university instructional practice. However, it often escapes the notice of the teachers and learners involved that neurodidactics is not simply a plausible concept – it can also be a myth if applied incorrectly. Numerous international studies show that both pre-service and in-service teachers as well as university educators endorse misconceptions on the topic of learning and the brain and orient their didactic conception on so-called neuromyths. This paper presents nine neuromyths on the topic of learning and memory. Based on a review of the current research, we discuss what determines their emergence and prevalence, to what extent neuromyths pose a problem for practice, and why and how both neurodidactics and neuromyths should be made an object of university instruction.
9 citations
TL;DR: In this article, the authors present and discuss recent findings from translational studies using cortisol and self-efficacy enhancement as an add-on to exposure therapy to improve the long-term effectiveness of exposure effects.
Abstract: Abstract Anxiety disorders (ADs) are characterized by increased chronicity and comorbidity with other ADs. Although exposure is the most effective therapy option for ADs, some patients show poor treatment response and a heightened vulnerability for relapse after treatment completion. Hence, significant research effort needs to be devoted to improve the long-term effectiveness of exposure effects. Recent attempts to increase exposure therapy efficacy use strategies aimed at promoting the acquisition and retrieval of extinction memories. The present review illustrates the value and limitations of such extinction-based therapy approaches. We present and discuss recent findings from translational studies using cortisol and self-efficacy enhancement as an add-on to exposure therapy. We illustrate how the integration of findings from experimental research on fear extinction learning and self-efficacy could advance the development of more optimized treatments for ADs.
6 citations
TL;DR: It is suggested that while the brain structure in transgender people is more similar to sex assigned at birth, it may shift with hormonal treatment, and on “sex-stereotypical tasks,” brain function may already be moreSimilar to gender identity in transgender persons, also before receiving gender-affirming hormone treatment.
Abstract: Transgender persons identify with a gender different from the one they were assigned at birth. Although describing oneself as transgender is not a new phenomenon, media attention has lately been increasing exponentially, thanks to progressive changes in laws and change in societal attitudes. These changes also allow more people nowadays to (openly) identify as transgender and/or seek gender-affirming treatment. However, simultaneously, not much is presently understood about the underlying neurobiology, and specifically the brain structure and brain function of transgender persons. One major question in neuroimaging and neuroscience has been to determine whether, at the brain level, transgender people resemble more their gender identity, their sex assigned at birth, or have a unique neural profile. Although the evidence is presently inconsistent, it suggests that while the brain structure, at least before hormonal treatment, is more similar to sex assigned at birth, it may shift with hormonal treatment. By contrast, on “sex-stereotypical tasks,” brain function may already be more similar to gender identity in transgender persons, also before receiving gender-affirming hormone treatment. However, studies continue to be limited by small sample sizes and new initiatives are needed to further elucidate the neurobiology of a ‘brain gender’ (sex-dimorphic change according to one’s gender).
5 citations
TL;DR: It is shown that AFM has made a significant contribution in studying the biophysics of cancer and the concept of mechanical fingerprints could find a wide variety of applications in biomedicine and medical diagnostics.
Abstract: Abstract Atomic Force Microscopy (AFM) is a powerful technique widely employed in biophysics, for instance to study topography of living cells and cell mechanics. Cell mechanics is a very interesting, biophysical parameter of cells, because it is strongly changed by various cellular processes, for example during cell division, cell movement, differentiation, aging, and also various diseases. Since cancer is a prominent example of changes in mechanical properties of diseases, the concept of the mechanical fingerprint has developed, which makes it possible to distinguish between healthy and diseased cells. In this article we report on various studies of cell mechanics with the AFM. We will first give a brief introduction on AFM principles and operational modes and then we will report on some applications of AFM in the field of cellular biophysics, like discriminating between healthy and cancer cells, as well as distinguishing cancer cells at different stages of malignancy. Overall, we will show that AFM has made a significant contribution in studying the biophysics of cancer and the concept of mechanical fingerprints could find a wide variety of applications in biomedicine and medical diagnostics.
4 citations
TL;DR: The role of stress and cortisol in the development of maladaptive emotional memories is presented and the mechanisms that may account for the cortisol-induced augmentation of exposure, namely, the enhancement of extinction memory consolidation and the reduction of the contextual dependency of the extinction memory are described.
Abstract: Abstract The glucocorticoid cortisol, a major player in the development of stress-related psychopathology, can also be used for the augmentation of extinction-based psychotherapies (e.g., exposure therapy). Substantial evidence supports its beneficial effects in the treatment of post-traumatic stress disorder and specific phobias. In this review, we first present the role of stress and cortisol in the development of maladaptive emotional memories. Then, we describe the mechanisms that may account for the cortisol-induced augmentation of exposure, namely, the enhancement of extinction memory consolidation and the reduction of the contextual dependency of the extinction memory. Finally, we discuss several considerations and limitations for the use of cortisol in psychotherapy, focusing on the possible adverse effects of cortisol in a reconsolidation-based (as opposed to extinction-based) intervention.
4 citations
TL;DR: It is essential to understand food reward and gut-brain signalling to find an effective strategy to combat the obesity pandemic, as increasing evidence that overconsumption of processed food distorts normal reward signalling, leading to compulsive eating behaviour and obesity.
Abstract: Abstract The increasing availability of ultra-processed, energy dense food is contributing to the spread of the obesity pandemic, which is a serious health threat in today’s world. One possible cause for this association arises from the fact that the brain is wired to derive pleasure from eating. Specifically, food intake activates reward pathways involving dopamine receptor signalling. The reinforcing value of specific food items results from the interplay between taste and nutritional properties. Increasing evidence suggests that nutritional value is sensed in the gut by chemoreceptors in the intestinal tract and the hepatic portal vein, and conveyed to the brain through neuronal and endocrine pathways to guide food selection behaviour. Ultra-processed food is designed to potentiate the reward response through a combination of high fat and high sugar, therebye seeming highly appetizing. There is increasing evidence that overconsumption of processed food distorts normal reward signalling, leading to compulsive eating behaviour and obesity. Hence, it is essential to understand food reward and gut-brain signalling to find an effective strategy to combat the obesity pandemic.
3 citations
TL;DR: It is outlined how targeting lysosomal function might help in developing novel therapeutic strategies in neurodegenerative disorders, including Parkinson’s disease.
Abstract: Abstract Lysosomes are cellular organelles that are important for the degradation and recycling of various biomolecules. Specialized lysosomal membrane proteins, as well as soluble enzymes, are important for the efficient turn-over of lysosomal substrates. A deficiency in the degradative capacity of lysosomes leads to severe pathologies referred to as lysosomal storage disorders. There is increasing evidence for the importance of lysosomal function in neurodegenerative disorders, including Parkinson’s disease. One reason for this might be the vulnerability of neuronal cells. Since neurons do not undergo further cell division, non-degraded substrates accumulate in aging cells, causing a buildup of toxicity. Recent genomic screenings identified a number of lysosome-associated genes as potential risk factors for Parkinson’s disease, which are discussed in this review. Moreover, it is outlined how targeting lysosomal function might help in developing novel therapeutic strategies.
3 citations
TL;DR: This mini-review indicates that the angiopoietin-Tie2 pathway does not only regulate blood vessel formation and stabilization but also simultaneously affect neuronal dendritogenesis in a cell-autonomous manner.
Abstract: Abstract Over the last two decades, it has become clear that classical molecules that regulate neurodevelopment also play an important role in directly regulating the development of the vascular system and vice versa. The prototypical angiogenic ligand vascular endothelial growth factor (VEGF) is by now also regarded as a molecular regulator of different neurodevelopmental processes, such as neuronal progenitor proliferation, migration and differentiation, dendritic and axonal branching and synaptogenesis. The direct effect of other classical angiogenic factors, such as angiopoietins and its receptor Tie2, on neurodevelopmental processes remains less defined. Recent work from our group indicates that the angiopoietin-Tie2 pathway does not only regulate blood vessel formation and stabilization but also simultaneously affect neuronal dendritogenesis in a cell-autonomous manner. In this mini-review, we will integrate our findings within the current understanding of the neurovascular link and within the previous knowledge of the potential effects of angiopoietins in the neuronal context.
2 citations
TL;DR: This review summarizes current knowledge on the formation, extinction, and return of pain-related memories with a focus on visceral pain and provides a conceptual background, describes experimental approaches, and summarizes findings on behavioral and neural mechanisms in healthy humans and patients with chronic pain.
Abstract: Abstract The role of pain-related fear learning and memory processes, conceptually embedded within the fear-avoidance model of chronic pain, is increasingly recognized. The unique biological salience of interoceptive, visceral pain with its cognitive, emotional, and motivational facets fosters associative learning. Conditioned fear is in principle adaptive but may turn maladaptive and contribute to hypervigilance and hyperalgesia in chronic pain. This review summarizes current knowledge on the formation, extinction, and return of pain-related memories with a focus on visceral pain. It provides a conceptual background, describes experimental approaches, and summarizes findings on behavioral and neural mechanisms in healthy humans and patients with chronic pain. Future directions underscore the potential of refining knowledge on the role of associative learning in the pathophysiology and treatment of chronic visceral pain in disorders of gut–brain interactions such as irritable bowel syndrome.
2 citations
TL;DR: The complexity of the SV cycle is starting to be comprehended, which opens new perspectives for the understanding of neuronal physiology and provides mechanistic explanations for several neurological and neurodegenerative diseases.
Abstract: Abstract The synaptic vesicle (SV) cycle, a trafficking pathway by which SV fuses with the plasma membrane to release neurotransmitters at the neuronal synapse, resides at the heart of neurotransmission. SV fusion consumes vesicle membrane and proteins, whose availability is limited, and these components must be recycled quickly to prevent synaptic fatigue. Biochemical, genetic and physiological approaches over the past five decades have led to a discovery of a large directory of proteins and lipids central to the SV cycle and several models on how these constituents account for the synapse function. The complexity of the SV cycle is starting to be comprehended, which opens new perspectives for our understanding of neuronal physiology and provides mechanistic explanations for several neurological and neurodegenerative diseases. Here, selected classic and recent insights into the mechanisms of two key SV trafficking steps (exocytosis and endocytosis) are reviewed, as well as their links to selected brain pathologies.
TL;DR: Three functionally defined pools of synaptic vesicles, namely the readily releasable, the recycling and the resting pool, are important structural subelements governing the ‘behavior’ of synaptic complexes within a given network such as the cortical column.
Abstract: Abstract Synapses are key elements in the communication between neurons in any given network of the normal adult, developmental and pathologically altered brain. Synapses are composed of nearly the same structural subelements: a presynaptic terminal containing mitochondria with an ultrastructurally visible density at the pre- and postsynaptic apposition zone. The presynaptic density is composed of a cocktail of various synaptic proteins involved in the binding, priming and docking of synaptic vesicles inducing synaptic transmission. Individual presynaptic terminals (synaptic boutons) contain a couple of hundred up to thousands of synaptic vesicles. The pre- and postsynaptic densities are separated by a synaptic cleft. The postsynaptic density, also containing various synaptic proteins and more importantly various neurotransmitter receptors and their subunits specifically composed and arranged at individual synaptic complexes, reside at the target structures of the presynaptic boutons that could be somata, dendrites, spines or initial segments of axons. Beside the importance of the network in which synapses are integrated, their individual structural composition critically determines the dynamic properties within a given connection or the computations of the entire network, in particular, the number, size and shape of the active zone, the structural equivalent to a functional neurotransmitter release site, together with the size and organization of the three functionally defined pools of synaptic vesicles, namely the readily releasable, the recycling and the resting pool, are important structural subelements governing the ‘behavior’ of synaptic complexes within a given network such as the cortical column. In the late last century, neuroscientists started to generate quantitative 3D-models of synaptic boutons and their target structures that is one possible way to correlate structure with function, thus allowing reliable predictions about their function. The re-introduction of electron microscopy (EM) as an important tool achieved by modern high-end, high-resolution transmission-EM, focused ion beam scanning-EM, CRYO-EM and EM-tomography have enormously improved our knowledge about the synaptic organization of the brain not only in various animal species, but also allowed new insights in the ‘microcosms’ of the human brain in health and disease.
TL;DR: This review describes the neural oscillations of non-rapid eye movement (NREM) sleep, the structures underlying these oscillations and their relation to hippocampus-dependent memory consolidation, and methods for modulating neural oscillation with the intent of affecting memory consolidation.
Abstract: Abstract Sleep contributes actively to the consolidation of many forms of memory. This review describes the neural oscillations of non-rapid eye movement (NREM) sleep, the structures underlying these oscillations and their relation to hippocampus-dependent memory consolidation. A main focus lies on the relation between inter- and intraregional interactions and their electrophysiological representation. Methods for modulating neural oscillations with the intent of affecting memory consolidation are presented.
TL;DR: The reader is introduced to the individual scientists who were awarded grants by the Schram Foundation over the years,some of the many discoveries made in the course of their studies and some of the key publications that arose from this work.
Abstract: Abstract Research driven solely by curiosity and the desire to understand fundamental principles of brain function. The freedom to address important questions with bold, sometimes risky experiments. A platform for open scientific exchange and discussions at highest academic level to provide new impulses to the field. And a growing number of scientists who share the passion for neuroscience and who join forces to tackle some of the big mysteries that surround the brain. These visions together with the deep conviction that basic research is the fundament needed for any progress in applied science motivated Dr. Armin Schram to create the foundation that carries his name. They are also the ideals that the foundation still pursues, and to date, 26 research proposals designed by individual researchers or small teams have been, or are, supported in this spirit. Here, we introduce the reader to the individual scientists who were awarded grants by the Schram Foundation over the years, highlight some of the many discoveries made in the course of their studies and list some of the key publications that arose from this work.
TL;DR: Methods and approaches to use optogenetics in the nervous and neuromuscular system of the nematode Caenorhabditis elegans to control the function of individual neurons, and behavioral, electrophysiological or electron microscopic analyses of circuit function and synaptic transmission are developed.
Abstract: Abstract In compact brains, circuits consisting of few neurons fulfill functions of entire brain systems in mammals. Thus, studying these small circuits can provide insights and guidelines also for the study of the human brain. We developed methods and approaches to use optogenetics in the nervous and neuromuscular system of the nematode Caenorhabditis elegans. These include single-cell expression and/or photoactivation of optogenetic tools, to control the function of individual neurons, and behavioral, electrophysiological or electron microscopic analyses of circuit function and synaptic transmission. We studied a number of circuits involved in locomotion, navigation and food searching; we addressed new genes in synaptic vesicle recycling, and we identified a novel pathway of neuromodulatory presynaptic plasticity. In our laboratory, support by the Schram foundation allowed me to explore new avenues of research especially during the early years of my career.
TL;DR: Experimental strategies aimed at reducing behavioral recovery after extinction of nonaversive experience are examined, focusing on extinction learning in multiple contexts, reminder cues, and the informational value of contexts.
Abstract: Abstract This review outlines behavioral and neurobiological aspects of extinction learning, with a focus on nonaversive experience. The extinction of acquired behavior is crucial for readaptation to our environment and plays a central role in therapeutic interventions. However, behavior that has been extinguished can reappear owing to context changes. In the first part of the article, we examine experimental strategies aimed at reducing behavioral recovery after extinction of nonaversive experience, focusing on extinction learning in multiple contexts, reminder cues, and the informational value of contexts. In the second part, we report findings from human imaging studies and studies with rodents on the neural correlates of extinction and response recovery in nonaversive learning, with a focus on ventromedial prefrontal cortex, hippocampus, and neurotransmitter systems.
TL;DR: It is shown that the avian extinction pathways are not identical but highly similar to those of mammals and that the human cerebellum processes prediction errors, a key element driving extinction of learned fear responses, and contributes to context-related effects of extinction.
Abstract: Abstract Extinction learning modifies the dynamics of brain circuits such that a previously learned conditioned response is no longer generated. The majority of extinction studies use fear conditioning in rodents and identified the prefrontal cortex, the hippocampus, and the amygdala as core regions of the extinction circuit. We sought to find answers to two questions: First, do we find a similar functional brain circuit in birds, which underwent a 300-million-year separate evolution from mammals? Second, do we have to incorporate the cerebellum as a key component of the central extinction circuit? We indeed show that the avian extinction pathways are not identical but highly similar to those of mammals. In addition, we reveal that the human cerebellum processes prediction errors, a key element driving extinction of learned fear responses, and contributes to context-related effects of extinction.
TL;DR: The clathrin-associated endocytic adaptor proteins that help to sort and recycle synaptic vesicles during presynaptic activity serve additional functions in the turnover of defective or aged synaptic components and in the retrograde axonal transport of important signaling molecules by regulating the formation or transport of autophagosomes.
Abstract: Abstract Communication in the central nervous system is based on the transmission of electrical signals at specialized junctions between nerve cells termed synapses. During chemical neurotransmission, tiny membrane spheres called synaptic vesicles that are packed with neurotransmitters elicit a postsynaptic response by fusing with the presynaptic membrane and releasing their content into the synaptic cleft. Synaptic vesicle fusion is followed by the reuptake of the membrane by endocytosis and the local reformation of functional synaptic vesicles within the presynaptic compartment to sustain further rounds of neurotransmitter release. Here, we provide an overview of the clathrin-associated endocytic adaptor proteins that help to sort and recycle synaptic vesicles during presynaptic activity. These adaptors also serve additional functions in the turnover of defective or aged synaptic components and in the retrograde axonal transport of important signaling molecules by regulating the formation or transport of autophagosomes. Endocytic adaptors thus play multiple roles in the maintenance of synaptic function. Defects in their expression or function can lead to neurodegenerative and neurological diseases.
TL;DR: How memory engrams emerge during learning is addressed in the dentate gyrus as the input gate of the hippocampus, which has an indispensable role in conscious memory formation, and how GABAergic interneurons may contribute to this process is examined.
Abstract: Abstract The hippocampus is decisive for the storage of conscious memories. Current theories suggest that experience-dependent modifications in excitation–inhibition balance enable a select group of neurons to form a new cell association during learning which represents the new memory trace. It was further proposed that particularly GABAergic-inhibitory interneurons have a large impact on population activity in neuronal networks by means of their inhibitory output synapses. They synchronize active principal cells at high frequencies, thereby supporting their binding to cell assemblies to jointly encode information. However, how cell associations emerge in space and time and how interneurons may contribute to this process is still largely unknown. We started to address this fundamental question in the dentate gyrus (DG) as the input gate of the hippocampus, which has an indispensable role in conscious memory formation. We used a combination of in vivo chronic two-photon imaging of population activity in the DG and the hippocampal areas CA1–3 of mice exposed to a virtual reality, in which they perform a goal-oriented spatial memory tasks, with high-density in vivo recordings and multiple whole-cell recordings in acute slice preparations, to determine how memory engrams emerge during learning. We further examine how GABAergic interneurons may contribute to this process. We believe that these lines of research will add to a better understanding on the mechanisms of memory formation in cortical networks.
TL;DR: This report explores how analyzing the nervous system of crustacean species from extreme habitats can provide deeper insights into the functional adaptations that drive the diversification of crustACEan brain structure.
Abstract: Abstract The current report focuses on shrimps from deep hydrothermal vents of the Mid-Atlantic Ridge that live in an environment characterized by high hydrostatic pressure, lack of sunlight, and with hot and potentially toxic emissions of black smoker vents. Malacostracan crustaceans display a large diversity of lifestyles and life histories and a rich repertoire of complex behavioral patterns including sophisticated social interactions. These aspects promote this taxon as an interesting group of organisms for those neurobiologists interested in evolutionary transformation of brain structures and evolutionary diversification of neuronal circuits. Here, we explore how analyzing the nervous system of crustacean species from extreme habitats can provide deeper insights into the functional adaptations that drive the diversification of crustacean brain structure.
TL;DR: In this review, some important historic and scientific aspects of the progress in understanding the role of the cholesterol transporter ApoE in the brain are summarized, and how the isoformApoE4 contributes to AD pathology is summarized.
Abstract: Abstract Age is the greatest risk factor for Alzheimer’s disease (AD). Today, due to an increase in global life expectancy, AD-related deaths are ranked as the sixth most common cause of death. The allele isoform ɛ4 of apolipoprotein E (ApoE4) is the most important genetic risk factor for AD. Three ApoE isoforms are common in humans: ApoE2, ApoE3, and ApoE4. ApoE3 is the most frequent isoform and considered neutral with regards to AD, whereas the isoform ApoE2 is protective. Thus it is important to understand how ApoE isoforms affect amyloid-β (Aβ) and tau toxicity, the key drivers of AD pathology. Aβ and tau accumulate to form the hallmarks of AD, plaques and neurofibrillary tangles, respectively. ApoE, primarily expressed by astrocytes, is the major lipid transporter in the brain. In this review I summarize some important historic and scientific aspects of our progress in understanding the role of the cholesterol transporter ApoE in the brain, and how the isoform ApoE4 contributes to AD pathology.
TL;DR: The neurobiological mechanisms underlying the extinction of conditioned immunosuppressive responses and the generalizability of the findings to other immunomodulatory drugs are investigated.
Abstract: Abstract Experimental studies in rodents and humans have convincingly demonstrated that immune functions can be modulated by associative learning processes. We have established a conditioned taste avoidance (CTA) paradigm in rats by pairing a novel taste (conditioned stimulus, CS) with an injection of the immunosuppressive drug cyclosporine A (CsA; unconditioned stimulus, US). Re-exposure to the CS results in a pronounced CTA and, more importantly, in a selective suppression of specific T-cell functions, mimicking the drugs’ effects. To provide a basis for using learned immunosuppressive strategies in clinical situations, we are currently investigating the neurobiological mechanisms underlying the extinction of conditioned immunosuppressive responses and the generalizability of our findings to other immunomodulatory drugs.