Epigenetic inheritance. Concepts, mechanisms and perspectives

Parents' stressful experiences can influence an offspring's vulnerability to many pathological conditions, including psychopathologies, and their effects may even endure for several generations. Nevertheless, the cause of this phenomenon has not been determined, and only recently have scientists turned to epigenetics to answer this question. There is extensive literature on epigenetics, but no consensus exists with regard to how and what can (and must) be considered to study and define epigenetics processes and their inheritance. In this work, we aimed to clarify and systematize these concepts. To this end, we analyzed the dynamics of epigenetic changes over time in detail and defined three types of epigenetics: a direct form of epigenetics (DE) and two indirect epigenetic processes-within (WIE) and across (AIE). DE refers to changes that occur in the lifespan of an individual, due to direct experiences with his environment. WIE concerns changes that occur inside of the womb, due to events during gestation. Finally, AIE defines changes that affect the individual's predecessors (parents, grandparents, etc.), due to events that occur even long before conception and that are somehow (e.g., through gametes, the intrauterine environment setting) transmitted across generations. This distinction allows us to organize the main body of epigenetic evidence according to these categories and then focus on the latter (AIE), referring to it as a faster route of informational transmission across generations-compared with genetic inheritance-that guides human evolution in a Lamarckian (i.e., experience-dependent) manner. Of the molecular processes that are implicated in this phenomenon, well-known (methylation) and novel (non-coding RNA, ncRNA) regulatory mechanisms are converging. Our discussion of the chief methods that are used to study epigenetic inheritance highlights the most compelling technical and theoretical problems of this discipline. Experimental suggestions to expand this field are provided, and their practical and ethical implications are discussed extensivel

Neuroeconomics processes underlying decision-making in joint vs individual actions: a behavioral and EEG study on non-human primates

A hallmark of the successful evolution of our species could reside in the ability to optimize collective behavior in order to achieve goals otherwise unattainable by acting alone. Inter-individual motor coordination can be considered as a key feature of sharing actions with others. As much as advantageous though, acting together can also be costly since it requires special cognitive and motor skills. We know that non-human primates are able to coordinate their actions in a dyadic context by dynamically adapting their motor behavior in a way that favors inter-individual synchronization. However, this type of behavioral adaptation has been proved to entail a cost, which is evident in a reduction of successful monkeys’ performance when sharing actions for a common goal. In the recent years, the existence of internal models of the own and the other’s action has been hypothesized by several authors, but how these models are formed and coded at the neural level is still object of study. The currently most accredited hypothesis is that acting with others requires the ability to integrate one’s own and others’ action representations in a dyadic motor plan. In order to better understand the behavioral and neural underpinnings of sharing actions, we conducted three experiments. In the first part of this work (Experiment 1) we investigated whether, how and under which task conditions monkeys can improve their performance in a joint action task. To address these questions, we have investigated the influence of a pre-instructing “social cue” providing anticipatory information about action context (individual or joint). Our findings suggest that pre-instructing the action context increase the chances of dyadic success by establishing an optimal “kinematic setting” that ultimately facilitates inter-individual motor coordination. Moreover, we speculate that such joint performance improvement can be ascribe to a successful resort to a “we-representation”, possible only when the joint action is pre-cued. In the second part of this thesis (Experiment 2) we aimed at investigating monkeys’ ability to estimate the cost of acting together and to use this information to decide between acting alone or jointly with a partner. To this aim we trained two monkeys to choose between two possible goals, each associated to different action types (solo or together) and payoffs. Our findings suggest that their economic choice was not merely dictated by the reward offered but also by the action cost, whereby motor inter-individual coordination was evaluated as more demanding than individual action. In the third and final part (Experiment 3) we conducted dual neural recordings using electroencephalography (EEG) while the monkeys were working on the same task adopted in Experiment 2. Preliminary results demonstrate that monkeys’ response evoked by the two offers was modulated by the action type chosen or expected to be chosen by the partner. This provides, for the first time, evidence of the feasibility of studying neural correlates underlying value-based decision making in non-human primates by mean of EEG methods

Epigenetic Inheritance: Concepts, Mechanisms and Perspectives

Parents’ stressful experiences can influence an offspring’s vulnerability to many pathological conditions, including psychopathologies, and their effects may even endure for several generations. Nevertheless, the cause of this phenomenon has not been determined, and only recently have scientists turned to epigenetics to answer this question. There is extensive literature on epigenetics, but no consensus exists with regard to how and what can (and must) be considered to study and define epigenetics processes and their inheritance. In this work, we aimed to clarify and systematize these concepts. To this end, we analyzed the dynamics of epigenetic changes over time in detail and defined three types of epigenetics: a direct form of epigenetics (DE) and two indirect epigenetic processes—within (WIE) and across (AIE). DE refers to changes that occur in the lifespan of an individual, due to direct experiences with his environment. WIE concerns changes that occur inside of the womb, due to events during gestation. Finally, AIE defines changes that affect the individual’s predecessors (parents, grandparents, etc.), due to events that occur even long before conception and that are somehow (e.g., through gametes, the intrauterine environment setting) transmitted across generations. This distinction allows us to organize the main body of epigenetic evidence according to these categories and then focus on the latter (AIE), referring to it as a faster route of informational transmission across generations—compared with genetic inheritance—that guides human evolution in a Lamarckian (i.e., experience-dependent) manner. Of the molecular processes that are implicated in this phenomenon, well-known (methylation) and novel (non-coding RNA, ncRNA) regulatory mechanisms are converging. Our discussion of the chief methods that are used to study epigenetic inheritance highlights the most compelling technical and theoretical problems of this discipline. Experimental suggestions to expand this field are provided, and their practical and ethical implications are discussed extensively

A cortical mechanism linking saliency detection and motor reactivity in rhesus monkeys

: Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFP) recorded from the dorso-lateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force: a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was maximal at the scalp vertex, highly reminiscent of the human 'vertex potential'. Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and, invasively, from the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to unexpected events

(4275) Proyectos Zero: activar la comunidad de prácticas para recibir a los nuevos alumnos de Arquitectura reorientando vocaciones y ampliando y diversificando la profesión de Arquitecto

Experiencia de innovación educativa sobre metodologías docentes del proyecto arquitectónico que permitan dirigir las vocaciones dispares de los estudiantes de primer año del Grado en Fundamentos de la Arquitectura llegados desde distintos perfiles de acceso a la Universidad gracias a la diversificación del perfil profesional del Arquitecto con ejemplos de jóvenes arquitectos cuyo ejercicio profesional amplía la imaginación del oficio que traen los estudiantes. Gracias al tema de trabajo común, el turismo, se experimenta y debate de forma lúdica el paradigma de la disciplina del Proyecto Arquitectónico heredado de la Modernidad y algunas de las alternativas contemporáneas

(4275) Proyectos Zero: activar la comunidad de prácticas para recibir a los nuevos alumnos de Arquitectura reorientando vocaciones y ampliando y diversificando la profesión de Arquitecto

Experiencia de innovación educativa sobre metodologías docentes del proyecto arquitectónico que permitan dirigir las vocaciones dispares de los estudiantes de primer año del Grado en Fundamentos de la Arquitectura llegados desde distintos perfiles de acceso a la Universidad gracias a la diversificación del perfil profesional del Arquitecto con ejemplos de jóvenes arquitectos cuyo ejercicio profesional amplía la imaginación del oficio que traen los estudiantes. Gracias al tema de trabajo común, el turismo, se experimenta y debate de forma lúdica el paradigma de la disciplina del Proyecto Arquitectónico heredado de la Modernidad y algunas de las alternativas contemporáneas