Rapid and Chronic Ethanol Tolerance Are Composed of Distinct Memory-Like States in Drosophila.

Ethanol tolerance is the first type of behavioral plasticity and neural plasticity that is induced by ethanol intake, and yet its molecular and circuit bases remain largely unexplored. Here, we characterize the following three distinct forms of ethanol tolerance in male Drosophila: rapid, chronic, and repeated. Rapid tolerance is composed of two short-lived memory-like states, one that is labile and one that is consolidated. Chronic tolerance, induced by continuous exposure, lasts for 2 d, induces ethanol preference, and hinders the development of rapid tolerance through the activity of histone deacetylases (HDACs). Unlike rapid tolerance, chronic tolerance is independent of the immediate early gene Hr38/Nr4a Chronic tolerance is suppressed by the sirtuin HDAC Sirt1, whereas rapid tolerance is enhanced by Sirt1 Moreover, rapid and chronic tolerance map to anatomically distinct regions of the mushroom body learning and memory centers. Chronic tolerance, like long-term memory, is dependent on new protein synthesis and it induces the kayak/c-fos immediate early gene, but it depends on CREB signaling outside the mushroom bodies, and it does not require the Radish GTPase. Thus, chronic ethanol exposure creates an ethanol-specific memory-like state that is molecularly and anatomically different from other forms of ethanol tolerance.SIGNIFICANCE STATEMENT The pattern and concentration of initial ethanol exposure causes operationally distinct types of ethanol tolerance to form. We identify separate molecular and neural circuit mechanisms for two forms of ethanol tolerance, rapid and chronic. We also discover that chronic tolerance forms an ethanol-specific long-term memory-like state that localizes to learning and memory circuits, but it is different from appetitive and aversive long-term memories. By contrast, rapid tolerance is composed of labile and consolidated short-term memory-like states. The multiple forms of ethanol memory-like states are genetically tractable for understanding how initial forms of ethanol-induced neural plasticity form a substrate for the longer-term brain changes associated with alcohol use disorder.

Hunger- and thirst-sensing neurons modulate a neuroendocrine network to coordinate sugar and water ingestion.

Consumption of food and water is tightly regulated by the nervous system to maintain internal nutrient homeostasis. Although generally considered independently, interactions between hunger and thirst drives are important to coordinate competing needs. In Drosophila , four neurons called the Interoceptive Subesophageal zone Neurons (ISNs) respond to intrinsic hunger and thirst signals to oppositely regulate sucrose and water ingestion. Here, we investigate the neural circuit downstream of the ISNs to examine how ingestion is regulated based on internal needs. Utilizing the recently available fly brain connectome, we find that the ISNs synapse with a novel cell type Bilateral T-shaped neuron (BiT) that projects to neuroendocrine centers. In vivo neural manipulations revealed that BiT oppositely regulates sugar and water ingestion. Neuroendocrine cells downstream of ISNs include several peptide-releasing and peptide-sensing neurons, including insulin producing cells (IPC), crustacean cardioactive peptide (CCAP) neurons, and CCHamide-2 receptor isoform RA (CCHa2R-RA) neurons. These neurons contribute differentially to ingestion of sugar and water, with IPCs and CCAP neurons oppositely regulating sugar and water ingestion, and CCHa2R-RA neurons modulating only water ingestion. Thus, the decision to consume sugar or water occurs via regulation of a broad peptidergic network that integrates internal signals of nutritional state to generate nutrient-specific ingestion.

Hunger- and thirst-sensing neurons modulate a neuroendocrine network to coordinate sugar and water ingestion.

Consumption of food and water is tightly regulated by the nervous system to maintain internal nutrient homeostasis. Although generally considered independently, interactions between hunger and thirst drives are important to coordinate competing needs. In Drosophila, four neurons called the interoceptive subesophageal zone neurons (ISNs) respond to intrinsic hunger and thirst signals to oppositely regulate sucrose and water ingestion. Here, we investigate the neural circuit downstream of the ISNs to examine how ingestion is regulated based on internal needs. Utilizing the recently available fly brain connectome, we find that the ISNs synapse with a novel cell-type bilateral T-shaped neuron (BiT) that projects to neuroendocrine centers. In vivo neural manipulations revealed that BiT oppositely regulates sugar and water ingestion. Neuroendocrine cells downstream of ISNs include several peptide-releasing and peptide-sensing neurons, including insulin producing cells (IPCs), crustacean cardioactive peptide (CCAP) neurons, and CCHamide-2 receptor isoform RA (CCHa2R-RA) neurons. These neurons contribute differentially to ingestion of sugar and water, with IPCs and CCAP neurons oppositely regulating sugar and water ingestion, and CCHa2R-RA neurons modulating only water ingestion. Thus, the decision to consume sugar or water occurs via regulation of a broad peptidergic network that integrates internal signals of nutritional state to generate nutrient-specific ingestion.

Tarjeta de evaluación de Propedéutica Clínica y Medicina Interna / Evaluation card in Clinical Propedeutics and Internal Medicine

Un dilema de las facultades y escuelas de Medicina ha sido la evaluación del progreso de los estudiantes a la largo de la carrera. Durante años esta evaluación estuvo dirigida solamente a medir los conocimientos que los estudiantes obtienen en cada disciplina académica. La evaluación del aprendizaje es una parte esencial del proceso de enseñanza-aprendizaje que nos posibilita su propia dirección, así como el control y la valoración de los modos de actuación que los estudiantes adquieren a través del desarrollo del proceso docente. Las estrategias para el desarrollo de las asignaturas, Propedéutica Clínica y Semiología Médica y de Medicina Interna, están diseñadas de manera tal que permita estimular a los estudiantes en su auto preparación y dotarlos de herramientas y conocimientos básicos en el desarrollo de habilidades necesarias al no contar en el consultorio médico con un registro permanente de las evaluaciones de los estudiantes en estas asignaturas, se decidió por el claustro de profesores de tercer año de la carrera pertenecientes al Policlínico Turcios Lima de Pinar del Río, durante el curso 2008-2009, confeccionar uno en forma de tarjeta que contemplara los principales aspectos a tener en cuenta en el desarrollo de los conocimientos y habilidades obtenidas por los educandos durante su estancia, con el objetivo de controlar de forma sistemática y uniforme la evaluación del estudiante en su desempeño en estas estancias como futuro Médico General Integral.

The evaluation of students' learning development along medical studies has been a dilemma for the medical schools and universities. During many years this evaluation was aimed at measuring knowledge acquisition in each academic discipline. Learning evaluation is an essential part of the teaching-learning process making its direction possible, as well as the control and the assessment of behavior manners that students acquire through the development of the teaching process. The strategies to learn about the development of the subjects: Clinical Propedeutics, Medical Semiology and Internal Medicine are designed to encourage students' self-training and to provide the basic tools and knowledge to develop the necessary skills. A permanent record to evaluate students' development in these subjects does not exist in the doctor's office; thus the teaching staff of the 3rd academic year at "Turcios Lima" Outpatient Teaching Clinic in Pinar del Rio (2008-2009), decided to prepare a card which includes the main aspects to be considered through the development of knowledge and skills during the stay-period with the purpose of controlling systematically and consistently the evaluation of the students' performance during the stay-period as future Comprehensive Doctors.