Starting up Program Research Master MSc Neuroscience. August 2017

Transcription

1 Starting up Program Research Master MSc Neuroscience August 2017

2 Date: August 21 1 September 2017 Location: Dept. of Neuroscience, Erasmus MC, Rotterdam Coordinator Introduction Programme: Prof.dr. Chris I. De Zeeuw Daily supervisor: Dr. Marcel de Jeu For information : Mrs. Loes Nijs / Mrs. Elise Buitenhuis Tel: 31 (0) masterneuroscience@erasmusmc.nl Copyright 2017 No part of this publication may be reproduced or distributed in any form or by any means without permission of the Department of Neuroscience, Erasmus MC, Rotterdam.

3 Contents 2017 Introduction 4 Programme overview 5 Programme week 1 8 Monday, August 21 Tuesday, August 22 Wednesday, August 23 Thursday, August 24 Friday, August 25 Programme week 2 14 Monday, August 28 Tuesday, August 29 Wednesday, August 30 Thursday, August 31 Friday, September 1 Appendix (articles) Distributed Synergistic Plasticity and Cerebellar Learning Gao Z, Van Beugen BJ, De Zeeuw CI 3

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5 Introduction Welcome to our Neuroscience Research Master Starting Up program. These weeks are designed for you with the intention to get to know each other, to stimulate your scientific interest and to facilitate the transition to the RM Neuroscience program. Modern neuroscience represents a merger of multiple disciplines including micro- and macroscopic neuroanatomy, cell physiology, molecular neurobiology, systems neurophysiology, cognitive neuroscience, and development and aging. All these disciplines are needed to understand the brain from the (sub)cellular up to the cognitive and clinical level. In this Starting Up program we will guide you through the basics of these disciplines and we will show you the large variety of research that is performed within our Neuroscience department. During the program, time will be reserved to work on your assignments. This way we hope to help you organize your time and get into the study modus of this research master. Apart from the scientific activities you are invited to join social events including Borrels on the first Monday and the Friday late afternoons. Moreover, there will be an informal dinner on Friday night September 1 while cruising the river Maas. Each day during your first week coffee, tea and lunch will be served. We look forward to getting to know you and trust this Starting Up program will give you a good introduction into the world of neuroscience. 5

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7 Programme overview Monday, August 21, Welcome and Introduction by prof.dr. CI De Zeeuw & dr. MTG de Jeu Baseline neuro knowledge test Lunch Ee1205* Evaluation Entry Exam Social event with 1st and 2nd year RM students Drinks Ee1205 Week 1 Tuesday, August 22, 2017 Micro- en macroscopic neuro-anatomy Lectures dr. TJH Ruigrok, dr. J Holstege Lunch Ee1205* Workshops dr. D Jaarsma, dr. TJH Ruigrok, E Haasdijk Wednesday, August 23, 2017 Cell physiology Lectures prof.dr. JGG Borst and dr. FE Hoebeek Lunch Ee1205* Workshops team Borst/Hoebeek Thursday, August 24, 2017 Motor learning at the molecular, cellular and behavioural level Lectures dr. Z Gao and prof.dr. CI De Zeeuw Lunch Ee1205* Workshops team De Zeeuw Friday, August 25, 2017 Neurodevelopment Lectures dr. D Jaarsma, dr. F de Vrij, dr. T van Ham Lunch Ee1205* Assignment for 'The Scientific Method', introduction prof.dr. JGG Borst MNEU Self study/preparation The Scientific Method Drinks Ee1205 Reception Graduation Ceremony *) during the first week, lunch will be provided 7

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9 Programme overview Monday, August 28, 2017 Systems physiology Lectures prof.dr. MA Frens and dr. J van der Geest Lunch time Workshops teams Frens/Van der Geest Week 2 Tuesday, August 29, 2017 Computational and applied Neuroscience Lectures dr. SKE Koekkoek, dr. MN Negrello, dr. C Strydis Lunch time MNEU Self study 'The Scientific Method' Wednesday, August 30, 2017 Neurological / Psychiatric Diseases Lectures by prof.dr. SA Kushner and prof.dr. Y Elgersma Lunch time Workshops teams Kushner/Elgersma Thursday, August 31, 2017 Assignment day MNEU Deadline 1st Assignment Scientific Method Discussion: baseline neuro knowledge test by dr. MTG Jeu Self study time Lunch time MNEU Self study 'Academic Writing' Friday, September 1, 2017 The Scientific Method MNEU Scientific Method (1) Lecture by prof.dr. JGG Borst Lunch time Course: general lab technics, lab rules and lab tours (E Haasdijk) Drinks Dinner, Boat Trip MS Contessa 9

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11 Monday 21 August 2017 Introduction Time: Activity: Welcome and Introduction by prof.dr. Chris de Zeeuw and dr. Marcel de Jeu Baseline neuro knowledge test This test will help you discover your neuroscience baseline so that we can address items of concern and enable you to prepare better for difficulties you may face Lunch in EE1205 Time: 13:00 14:00 Activity : Evaluation Entry Exam, Introduction SURE Time: 14:00 16:00 Activity: Social Event 1 st and 2 nd year RM students Time: Location: 12 th Floor Faculty Building Activity: Reception 11

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13 Tuesday 22 August 2017 Microscopic and macroscopic neuroanatomy Time: Activity Lecture 1: Neurons and Glia: building blocks of the nervous system Faculty: Dr. Joan Holstege Coffee break This lecture will review the general morphology of nerve cells. The four distinct compartments that make up all nerve cells (dendrites, soma, axon, terminals) will be illustrated and detailed in microscopic and ultramicroscopic perspective. Obvious formfunction relations between various types of nerve cells will be highlighted. In addition, typology and functions of the nonnervous constituents of the brain, i.e. the glial cells will be briefly reviewed. Time: Activity Lecture 2: Organization of the central nervous system Faculty: Dr. Tom Ruigrok This lecture will review the basic macroscopic and microscopic organization of the central nervous system and its link with the development of the ventricular system of the brain. The comparative anatomy of the human brain and of popular research animals such as rat and mice will be briefly discussed. The organization of the sensory-motor system will be used to illustrate key elements of the functional organization of the nervous system Lunch in EE1205 Time: Location: Various Activity: Workshop: Working with sections Faculty: Dr. Tom Ruigrok, Dr. Dick Jaarsma, Elize Haasdijk 13

14 This workshop consists of three parts (A, B, C) that will illustrate techniques to prepare and analyze sections of brain tissue that are used to study the anatomy of the nervous system. Students will rotate and will get hands on opportunity to work with brain sections in three fields. Part A: Sectioning and mounting brain slices For careful analysis of the constituents and connections within the nervous system of experimental animals, it is usually necessary to section the brain. In this workshop you will see and experience cutting brain sections with a freezing microtome. After preparing and rinsing these sections, diverse histological procedures may be executed on the sections. Eventually, in order to enable microscopic examination, sections need to be mounted on glass slides. In this part of the workshop you will practice the basic skill of sectioning, rinsing, ordering and mounting free floating sections. Part B: Analysis of section by optic (light) microscopy In this part of the workshop you will work with a light microscope and learn to examine sequential series of sections from several neuroanatomical experiments. In this way you can evaluate i) injection site, ii) type of tracing (anterograde/retrograde or both), iii) draw conclusions from the results. Part C: Analysis of sections by digital microscopy Stained tissue sections are increasingly being scanned at high resolution to allow subsequent analysis on a computer. Here you will study the same sections as in part B using this digital microscopic approach. In addition you will examine brain images from the Allen Brain Atlas ( a large online high-resolution atlas of gene expression throughout the adult and developing mouse brain.

15 Wednesday 23 August 2017 Cell Physiology Time: Activity: Lecture 1: Cell Physiology Faculty: Prof.dr. Gerard Borst Coffee break One of the striking properties of the central nervous system is the enormous diversity in the morphology and the firing patterns of different neurons. This lecture will review which ion channels are responsible for the different firing patterns of neurons, how these firing characteristics contribute to neuronal communication, and which mechanisms are used by a neuron to integrate the information it receives. Time: Activity: Lecture 2: Methods in Cell Physiology Faculty: Dr. Freek Hoebeek The possibilities to record the activity of neurons have enormously expanded in recent years. Apart from the patch-clamp techniques, different optical sensors are now available that allow to measure neuronal signals with subcellular resolution, or to manipulate neuronal activity. As an introduction to the workshop of the afternoon, these different methods will be discussed Lunch in EE1205 Time: Location: Various Activity: Workshops In the afternoon the students will be attending workshops, which will focus on different aspects of cell physiological recording techniques in brain slices or in vivo. 15

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17 Thursday 24 August 2017 Motor learning at the molecular, cellular and behavioural level Time: Location: Ee1473 Lecture 1: Molecular and cellular mechanisms underlining motor learning Dr. Zhenyu Gao Coffee break Time: Location: Ee1473 Lecture 2: Behavioural screening for cerebellar dependent learning deficits Prof.dr. Chris de Zeeuw Abstract: These two lectures will give a comprehensive overview of the plasticity and learning mechanisms in the cerebellar cortex that control motor behaviour and learning. The first lecture will discuss the molecular pathways involved in persistent changes in synaptic strength. These changes have been described for both inhibitory and excitatory synapses onto Purkinje cells. Impaired plasticity at these synapses, in turn, has been correlated to deficits in motor learning. The different ways of examining motor learning in mice will be addressed in the second lecture. This lecture will go into the phenotypes that are related to deficits in synaptic plasticity, and briefly introduce the different behavioural tasks that test cerebellar functioning. Each of these tasks will then be demonstrated during the workshops in the afternoon. Preparation: - Gao, Van Beugen and De Zeeuw (2012) Nat. Rev. Neurosci. - Kandel et al., 5 th edition, The Cerebellum, pp Lunch in EE

18 Tuesday, August 30th: Afternoon workshop Time: Activity: Explanation and split up in groups for various workshops Room Ee 1208: Erasmus Ladder Group 1: Group 2: Tea break Group 3: Group 4: Room Ee 1275/ Ee1229: Classical eyeblink conditioning Henk-Jan Boele Group 2: Group 1: Tea break Group 4: Group 3: Room Ee 1233: Whisker based object localization task Vincenzo Romano Group 3: Group 4: Tea break Group 1: Group 2: Room Ee 1257: VOR adaptation Bin Wu Group 4: Group 3: Tea break Group 2: Group 1:

19 Friday 25 August 2017 Neurodevelopment Time: Activity: Lecture 1: Introduction in neurodevelopment Faculty: Dr. Dick Jaarsma, dept of Neuroscience Coffee break The making of a central nervous system consisting of more than 80 billion interconnected neurons is an gigantic task. It starts with the development of a simple tube, that subsequently grows and bends and becomes more and more specialised. Neurons are generated in specific locations at different time points and often have to make a small journey to reach their final destination. Then the axon has to find the target neurons and make the proper connections. The complexity of nervous system development is illustrated by the large variety of abnormalities that result from defects in specific neurodevelopmental steps. This lecture will provide a global overview the formation and early patterning of the neural tube, neurogenesis and neuronal migration. Time: Activity: Lecture 2: Making neurons and brains in a dish Faculty: Dr. Femke de Vrij, dept. of Psychiatry Nowadays it is possible to culture brain tissue (brain organoids) in a dish by reprogramming non-neuronal cells such as, for instance, cells from your skin into stem cells. These induced pluripotent stem cells resemble embryonic stem cells and have the capacity to differentiate into any cell type, including the diversity of specialized cells of the brain. This lecture will provide some insight how to do this, and the potential applications of these approaches to study brain disorders. Time: Activity: Lecture 3:Zebrafish as a model for neurodevelopment Faculty: Dr. Tjakko van Ham, dept. of Neurogenetics The small tropical zebrafish is a powerful system to model human diseases and discover new targetable molecular pathways to treat disease. The zebrafish is 19

20 particularly suited for genetic studies and in vivo brain imaging approaches. using multiphoton imaging as well as genome editing and lineage tracing. Taking advantage of transparent zebrafish mutants, axonal growth and neuronal activity can be visualised from the outside of the animal Lunch in EE1205 Time: Activity: Self study, preparation for Scientific Method Introduction by Gerard Borst Time: Location: 12 th Floor Faculty Building Activity: Drinks!

21 Monday 28 August 2017 System Physiology Time: Activity: Lecture 1: Introduction to System Physiology Faculty Prof.dr. Maarten Frens In this lecture we will introduce the method adopted by our group to study the human brain. The system physiology approach is described by means of a case study in which molecular, cellular and behavioural approaches were used to delineate the cerebellar motor deficits in a rare neurological patient. Time: Activity: Lecture 2: Experiments in System Physiology Faculty: Dr. Jos van der Geest In this lecture we will describe a few of the experiments uses by our group in more detail. We will focus on functional MRI and eye movements Lunch in EE1205 Afternoon: Tour des Labs 2017 A interactive visit to the Systems Physiology lab, including demonstrations by Maarten Frens, Jos van der Geest, Zeb Jonker, Johan Pel, and Patrick Forbes 21

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23 Tuesday 29 August 2017 Computational and applied Neuroscience Time: :00 Location: Ee1473 Activity: Lectures Faculty: Dr. MN Negrello, dr. C Strydis, dr. SKE Koekkoek Neural Computation and Computational Neuroscience (M. Negrello) This lecture describes the different goals of the similar sounding but rather distinct fields of neural computation and of computational neuroscience. While computational neuroscience attempts to simulate neurons and networks with attention to biophysical detail, neural computation has the goal of understanding how collections of neurons give rise to cognitive function. Neural Interfaces: Reading from and writing to the brain This lecture will introduce the problems of BCI Brain Computer Interfaces. What does it mean to read from and write to the brain? What are the technological paths that will bring us to emulate parts of the brain? What are the main successes and the main challenges involved? Lunch in EE1205 Time: Location: Ee1473 Activity: Preparation for assignment for The Scientific Method Faculty: self study 23

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25 Wednesday 30 August 2017 Neurological / Psychiatric Diseases Time: Location: Ee1473 Activity: Lecture 1: Using ipsc-based models for neuropsychiatric disease modeling Faculty: Prof.dr. Steven Kushner Coffee break Psychiatric and neurological disorders impose among the heaviest burden for patients, families and society. However, there is yet no satisfying explanation for the biological mechanisms underlying these disorders, due to the extraordinary complexity of the brain and the difficulties inherent in studying human neurophysiology. Towards the goal of establishing standardized methods for investigating the (patho)physiology of human brain disorders, we have developed novel state-of-the-art methods for differentiating physiologically active three-dimensional (3D) neuronal networks from human patient-derived induced pluripotent stem cells, offering the unique opportunity to investigate the molecular and cellular pathophysiology of disease initiation and progression. In my lecture, I will discuss the detailed implementation of this methodology and the electrophysiological properties of the resulting neuronal networks. Moreover, I will describe the successful application of this methodology for revealing fundamental insights into the neurobiology of schizophrenia using a family-based design supported by next-generation sequencing. Time: Location: Ee1473 Activity: Lecture 2: Molecular mechanisms underlying neurodevelopmental disorders: from mechanism to treatment. Faculty: Prof.dr. Ype Elgersma Genetic disorders present us with the unique knowledge of knowing the causal gene and study the impact of the genetic mutation in mouse models of disease. Because of these mouse models, insight in the molecular and cellular basis of the neurological deficits associated with childhood developmental disorders gains rapid progress. In order to be successful in finding a treatment that can ameliorate the neurological deficits, several hurdles must be taken. First, the mouse model must be a good for the disease, and capture its most distinguishing features. Second, the molecular and cellular mechanism that is underlying the disorder must be identified. It must be ensured that the identified mechanism is 25

26 directly underlying the pathology, and not the result of a homeostatic compensation mechanism. Third, a suitable drug must be found that targets the identified pathological mechanism, and demonstrates reversibility of the affected processes. The fourth and ultimate step is of course to test the toxicity and efficacy of the potential drug in a clinical trial. In this presentation, I will describe basal and clinical research performed at the Dutch ENCORE center for neurodevelopmental disorders. Specifically, I will present novel insights in the pathophysiology underlying Angelman syndrome (AS) and Tuberous Sclerosis Complex (TSC). I will also discuss how these new findings can be translated to clinical trials Lunch in EE1205 Time: Location: Ee1473 Activity: Workshops Faculty: Elgersma and Kushner

27 Thursday 31 August 2017 Assignment Day Deadline: hrs. - assignment The Scientific Method Time: Location: Ee1473 Activity: Discussion baseline neuro knowledge test First assignment Academic Writing Faculty: Dr. Marcel de Jeu, Self study Lunch in EE1205 Time: Activity: Assignment Academic Writing Faculty: Self study 27

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29 Friday 1 September 2017 The Scientific Method Time: Activity: Lecture The Scientific Method (1) Faculty: prof.dr. JGG Borst The main topic of these meetings will be how you can ensure that the experimental results you obtain during your masters can be reproduced by others. We will also discuss related questions such as: - How do you come up with a well-founded research question? - How does one plan an experiment and analyze its results? Lunch in EE1205 The lab Time: 13:00 13:30 Location: EE1270 Activity: Pass photo for photoboard of department Time: 13:30-16:30 Location: various Activity: Lab Techniques, tour and rules (Elize Haasdijk) In groups : You will get a guided tour around the department You will be shown the different aspects of working in a lab, involving o Basic lab rules o Safety instructions o Working with antibodies, gasses and chemicals o How to work with mice o Information about the digital Neuroscience Immuno Track System (NITS) o How to use a pipet Your memory will be refreshed concerning your knowledge of Chemical calculations and how to make a simple buffer. 29

30 Drinks in EE Dinner on MS Contessa