W1 Lectures PDF - Biological Foundations of Mental Health

12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Prof Sarah Guthrie To...

12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Prof Sarah Guthrie Topic 1 Week 1: Overview of CNS development Introduction to brain anatomy Part 1 of 3 Introduction The levels of neural development - O The systems level: changes in size and shape in the development of nervous system – ‘morphogenesis’ - The cellular level : ‘differentiation’ from progenitors to mature - - Figure 1: Morphogenesis neurons - Developmental disorders that affect mental health Figure 2: Differentiation Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 2 of 10 1  12/09/2018 Overview of human development (1) Day 0 Fertilisation, Cleavage Day 14 Gastrulation – transformation of the 2-layered disk into 3 ‘germ’ layers – ectoderm, mesoderm Day 7 and endoderm give rise to all tissues Blastocyst, implantation – formation of the embryonic disk with 2 layers, epiblast and hypoblast Figure 3: Overview of human development Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 3 of 10 Overview of human development (2) Day 21 Week 4-5 Neurulation – creation of the Embryo recognisable with a head embryonic nervous system from the and tail – ‘tailbud’ stage ectoderm Week 4-8 3rd Month – Birth Embryonic Period Organogenesis occurs Foetal Period Main tissue and organ Maturation of tissues systems develop and organs Major features of body Rapid growth of the body form develop Cell proliferation Figure 4: Overview of human development Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 4 of 10 2  12/09/2018 Neural induction Ectoderm is induced to become neural tissue by the underlying mesoderm. neural induction In the process of neurulation, morphogenic and genetic changes transform section of the ectoderm into the neural tube. Figure 5: Neural induction Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 5 of 10 Early neurulation Surface view Transverse view Figure 6: Early neurulation Figure 7: Scanning electron micrograph of human embryo Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 6 of 10 3  12/09/2018 Late neurulation Surface view Transverse view Figure 8: Late neurulation Figure 9: Scanning electron micrograph of human embryo Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 7 of 10 Morphogenesis Cranial and caudal folding arches the embryo into a “comma” shape. Figure 10: Tailbud stage (4-5 weeks) Figure 11: 5-week old embryo Figure 12: 5-week old embryo Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 8 of 10 4  12/09/2018 Many organisms look similar at the tailbud stage Figure 13: Double Plate Illustration Showing Embryos of fish (F), Salamander (A), Turtle (T), Chick (H), Pig (S), Cow (R), Rabbit (K), and Human (M) Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 9 of 10 Formation of the flexures and subdivisions in the neural tube 26 days 28 days 35 days Figure 14: Formation of the flexures and subdivisions in the neural tube Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 10 of 10 5  12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Prof Sarah Guthrie Topic 1 Week 1: Overview of CNS development Introduction to brain anatomy Part 2 of 3 Differentiation homogeneous cell population cell interactions developmental time differentiated cell types Figure 15: Waddington’s epigenetic landscape, a metaphor for development and how Figure 16: Differentiation – the process over developmental time whereby an cells make ‘decisions’ to arrive at their ‘fates’ initially homogeneous cell population gives rise to different cell types Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 2 of 10 1  12/09/2018 Aspects of neuronal differentiation dendrites Morphology Gene expression Neurotransmitter Axon projections and connections axon Figure 17: Cerebellar purkinje neuron Figure 18: Cortical pyramidal neuron Figure 19: Pyramidal neuron image Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 3 of 10 The developmental steps that lead to differentiation Neurogenesis Cell migration Axonogenesis Synaptogenesis Cell death or pruning Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 4 of 10 2  12/09/2018 Neurogensis pial surface radial glial cells neural tube ventricular surface radial glial cells pial surface differentiating mantle zone neuron axon section through neural tube ventricular zone ventricular surface Time Figure 20: The generation of neurons from radial glial cells Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 5 of 10 Neuronal migration Dorsal Ventral Radial migration gives rise mainly to excitatory projection neurons Tangential migration gives rise mainly to inhibitory interneurons Neural crest cells migrate away from the neural tube to form dorsal root ganglia and sympathetic ganglia Figure 22: Migration of the neural crest cells to generate peripheral ganglia Figure 21: Neuronal migration in the developing telencephalon Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 6 of 10 3  12/09/2018 Axonogenesis (1) A single axon forms from several symmetrical processes in hippocampal neurons in vitro Stage 1 Stage 2 Stage 3 post-mitotic neuron post-mitotic neuron with symmetry breaking produces symmetrical processes one axon and several dendrites Stage 4 Stage 5 the axon grows longer and axon and dendrites branch a neuronal network with synapses forms Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 7 of 10 Axonogenesis (2) post synceptic pre-synaptic. Molecular cues guide axons to their targets (nerves, glands or muscles) Post-synaptic Pre-synaptic => Synapse types: Axo-dendritic Axo-somatic Axo-axonic Figure 23. An axon grows towards its target neuron where it will form a synapse Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 8 of 10 4  12/09/2018 Synaptogenesis Pre-synaptic Post-synaptic Neuroligin 1 Neuroligin 2 Excitatory synapses Inhibitory synapses Figure 24: Stages of synaptogenesis Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 9 of 10 Cell death and pruning Pruning can occur to axons and dendrites, which disintegrate and the debris is cleared away Cell death and pruning may eliminate unwanted neurons or connections, match numbers of pre and post-synaptic cells, and ensure that synaptic transmission and circuit function is optimised Figure 25: Synapse pruning Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 10 of 10 5  12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Prof Sarah Guthrie Topic 1 Week 1: Overview of CNS development Introduction to brain anatomy Part 3 of 3 Neurodevelopmental disorders that affect mental health anderst Dentieapheffecte * Examples of human disorders which can be caused by defective developmental processes: * Autistic spectrum disorder = Schizophrenia = Childhood onset epilepsy = X-linked mental retardation = We now know some of the genes that are mutated in humans with these disorders. Developmental neuroscientists are trying to unravel how these mutations lead to the disorders. It appears that dendrite and synapse development are often affected by these gene mutations. Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 2 of 8 1  12/09/2018 Case study: Synaptogenesis and autistic spectrum disorder (ASD) Studies in humans have shown that mutations in several genes including Neuroligin4 (Nlgn4) are linked to autistic spectrum disorder Nlgn4 is involved in synapse development and markers of inhibitory synapses are reduced in Nlgn4 knockout (KO) mice Nlgn4 knockout (KO) mice show behavioural changes reminiscent of ASD, such as impairments in social interactions and communication, repetitive behaviours and interests Figure 26: Defects in synaptogenesis play a role in ASD Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 3 of 8 area Case study: Dendritic spine development and schizophrenia/ASD Schizophrenia which Fragile X mental retardation syndrome Normal Fragile X The number of dendritic spines is reduced in the Mice lacking the Fragile X - - dorsolateral prefrontal cortex of some schizophrenic mental retardation protein subjects have more immature, thin spines normal similiarmans subject C e schizophrenic subjects Figure 27: Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia The process of dendrite development and/or pruning Figure 28: Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome is implicated in schizophrenia and ASD Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 4 of 8 2  12/09/2018 Neurodevelopmental disorders that affect mental health Research in developmental neuroscience will help us understand neurodevelopmental disorders and mental health and vice versa Live imaging of development is scaling new heights & Advanced behavioural tests can mimic some aspects of human behaviour in the mouse Identification of genes mutated in human populations can then lead to studies in animal models Identification of genes through developmental neurobiology can be screened for mutations in humans Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 5 of 8 Figure references (1) 1. Figure 1. ‘Embryo Week 9-10’. Flickr - Photo Sharing! Accessed 4 8. Figure 8. ‘Early neurulation ~3 weeks’. Image created by King’s January 2016. http://bit.ly/morphoGen. Used under the Creative College London. commons licence: http://bit.ly/CreativeCom 9. Figure 9. Hill, M.A. (2016) Embryology Stage10 sem9.jpg. 2. Figure 2. ‘Differentiation’, image generated by King’s College Retrieved January 11, 2016, from London. https://embryology.med.unsw.edu.au/embryology/index.php/Fil 3. Figure 3. ‘Trends in Animal Evolution’. Accessed 19 February e:Stage10_sem9.jpg 2016. http://www.zo.utexas.edu/faculty/sjasper/images/32.1.gif 10. Figure 10. Hill, M.A. (2016) Embryology Stage13 sem1c.jpg. 4. Figure 4. ‘Overview of human development’, image created by Retrieved January 11, 2016, from King’s College London. https://embryology.med.unsw.edu.au/embryology/index.php/Fil e:Stage13_sem1c.jpg 5. Figure 5. ‘Neural Induction’, image crated by King’s College London. 11. Figure 11. Hill, M.A. (2016) Embryology Stage12 sem1.jpg. Retrieved January 11, 2016, from 6. Figure 6. ‘Early neurulation ~3 weeks’, image created by King’s https://embryology.med.unsw.edu.au/embryology/index.php/Fil College London. e:Stage12_sem1.jpg 7. Figure 7. Hill, M.A. (2016) Embryology Stage10 sem6.jpg. 12. Figure 12. Image of embryo, created by King’s College London. Retrieved January 11, 2016, from https://embryology.med.unsw.edu.au/embryology/index.php/Fil e:Stage10_sem6.jpg Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 6 of 8 3  12/09/2018 Figure references (2) 13. Figure 13. Engelmann, Lithograph by J. G. Bach of Leipzig after 17. Figure 17 & 18. Kandel, Eric R., James H. Schwartz, and Thomas drawings by Haeckel, from Anthropogenie published by. English: M. Jessell. Principles of Neural Science, Fifth Edition. 5 edition. Double Plate Illustration Showing Embryos of fish (F), Salamander New York: McGraw-Hill Medical, 2012. (A), Turtle (T), Chick (H), Pig (S), Cow (R), Rabbit (K), and Human 18. Figure 19. ‘Pyramidal neuron’, image generated by King’s College (M), at ‘Very Early’, ‘Somewhat Later’ and ‘Still Later’ Stages, London. from Haeckel’s Anthropogenie Published in 1874, 1 October 1874. Nick Hopwood. ‘Pictures of Evolution and Charges of 19. Figure 20. ‘Cell division’, image created by King’s College London. Fraud:: Ernst Haeckel’s Embryological Illustrations’, Isis 97 (2006), 20. Video: ‘Neurogenesis’, courtesy of Prof Jon Clarke and Dr Una 260-301 pdf. Ren. https://commons.wikimedia.org/wiki/File:Haeckel_Anthropogeni 21. Figure 21. ‘Neuronal Migration’, image created by King’s College e_1874.jpg. London. 14. Figure 14. Image created by King’s College London. 22. Figure 22. ‘Neural Crest Migration’, image created by King’s 15. Figure 15. ‘Waddington’s Epigenetic Landscape, and Being College London. “optimally Autistic” | DART’. Accessed 11 January 2016. 23. Figure 23, ‘Axonogenesis’, image created by King’s College http://www.dart.ed.ac.uk/optimally-autistic/. London. 16. Figure 16. ‘Differentiation’, image created by King’s College 24. Figure 24. ‘Stages of synaptogenesis’, image created by King’s London. College London. 25. Figure 25. Synapse Pruning, “Nervous System”, Accessed January 13, 2016. https://universe-review.ca/R10-16-ANS12.htm. Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 7 of 8 Figure references (3) 26. Figure 26. ‘Inhibitory Synapses in the CA3 Stratum Pyramidale of Nlgn4 Kos’, from Hammer, Matthieu, Dilja Krueger-Burg, Liam Patrick Tuffy, Benjamin Hillman Cooper, Holger Taschenberger, Sarit Pati Goswami, Hannelore Ehrenreich, et al. “Perturbed Hippocampal Synaptic Inhibition and γ-Oscillations in a Neuroligin-4 Knockout Mouse Model of Autism.” Cell Reports 13, no. 3 (October 20, 2015): 516–23. doi:10.1016/j.celrep.2015.09.011. p. 518. This article is available under the terms of the Creative Commons Attribution License (CC BY). 27. Figure 27. ‘Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia’, Glantz LA, and Lewis DA. Archives of General Psychiatry 57, no. 1 (1 January 2000): 65–73. doi:10.1001/archpsyc.57.1.65. 28. Figure 28. ‘Dendritic Spine Structural Anomalies in Fragile-X Mental Retardation Syndrome’, Scott A. Irwin, Roberto Galvez and William T. Greenough, Cereb. Cortex (2000) 10 (10): 1038- 1044.doi: 10.1093/cercor/10.10.1038 Week 1 Introduction to brain anatomy Week Topic 1: Overview of CNS 2 – Lorem ipsum development 8 of 8 4  Module: Biological foundations of mental health Week 1 Introduction to brain anatomy Topic 1 Overview of CNS development - Part 3 of 3 Professor Sarah Guthrie Professor of of Developmental Neurobiology Lecture transcript Slide 2 Examples of human disorders which can be caused by defective developmental processes are autistic spectrum disorder, schizophrenia, childhood onset epilepsy, and X-linked mental retardation. In this section, we will highlight certain developmental aspects of ASD and schizophrenia. Understanding the developmental processes I have described in this subtopic is extremely important, as this can give insight into neurodevelopmental disorders in humans. Large-scale human genetic screenings and experiments in animal models have started to uncover some of the principles that underlie these disorders. We now know some of the genes that are mutated in humans with these disorders. Developmental neuroscientists are trying to understand the mechanisms that underlie the changes caused by these mutations. by these gene mutations. Many aspects of development can be perturbed to lead to such disorders, such as axon growth, guidance, neuronal migration, synapse formation, and function. Slide 3 Autistic spectrum disorder, ASD, is an umbrella term for a disorder which can take on multiple forms and have multiple causes. Nevertheless, it is clear that ASD is a neurodevelopmental disorder and that some forms of ASD are genetically based. In humans, it has been shown that mutations in several genes including neuroligin-4 are linked to autistic spectrum disorder. Neuroligin-4 is involved in synapse development. Studies using mice, inhibitory synapses are reduced in some areas of the hippocampus, pointing to a developmental defect. inhibitory synapses-- gephyrin and a GABA A receptor subunit. Compared to the wild-type panels to the left, there’s a reduction in the staining in the neuroligin for KO, or knockout, mouse. In addition, neuroligin for knockout mice showed behavioural changes reminiscent of ASD. It’s perhaps surprising that it’s been possible to model some of the behavioural aspects of ASD in mice using assays of, for example, social interaction or vocalisation. These experiments have shown that neuroligin for knockout mice showed impairments in social interaction and communication, as well as repetitive behaviours and interests. Some of these features are characteristic of humans with ASD. Whereas the process of synaptogenesis and its link to behaviour is extremely complex, these Transcripts by 3Playmedia Week 1 © King’s College London 2019 1.  studies give us hope that ASD can be modelled using the mouse as an experimental system. Slide 4 As well as changes in the numbers of synapses, there may be changes in the structural features of dendrites and dendritic spines which are key to synapse formation. There is a large amount of evidence now to show that the numbers, shape, and development of dendritic spines change in some individuals with schizophrenia or ASD including X-linked mental retardation, Fragile-X, which has features of ASD. The number of dendritic spines is reduced in the dorsolateral prefrontal cortex of some schizophrenia subjects. dendritic spines in a normal subject. In the two schizophrenia subjects shown, you can see that the dendrite development and/or pruning. Mice lacking the Fragile-X mental retardation protein have more immature, thin spines, and there is dendrite from the wild-type animal with a mouse used as a model for Fragile-X and lacking the FMRP protein. Knowledge about the genes and proteins which are involved in dendritic spine development and testing their role using animal models will be key to understanding the link between spine development, function, and mental health. It’s worth bearing in mind, however, that there are a large variety of studies on issues such as dendritic spine development, density, and maturation. Some of draw general conclusions from this work. Slide 5 We can conclude that understanding development in detail can unlock many of the secrets of the way the nervous system is built and how it later functions. Research in developmental neuroscience will help us understand neurodevelopmental disorders and mental health and vice versa, Many next decades in unravelling these principles. For example, live imaging in vivo using the mouse and pruning, and plasticity. and proteins on behaviour at the organism level. Genetic screens in humans can then reveal the genes whose function can be tested in animals, while genes shown to be important in development through basic science studies can be screened in the human population. This interplay will be the foundation of future discoveries in development and mental health. Transcripts by 3Playmedia Week 1 © King’s College London 2019 2.  Module: Biological foundations of mental health Week 1 Introduction to brain anatomy Topic 1 Overview of CNS development - Part 2 of 3 Professor Sarah Guthrie Professor of of Developmental Neurobiology Lecture transcript Slide 2 Now we will consider neural development as it applies to the individual cell level. During development, a process where cells progress from a ‘multipotent’ population, capable of producing a range of cellular derivatives, to cells of particular, specialised identities, or ‘fates’. developmental step. tree, which will eventually lead to cells assuming one of a number of fates. Slide 3 whereas the pyramidal neuron resides in the cerebral cortex and is less elaborate, with an apical dendrite and some branches. Both neurons have an axon which extends downwards in the diagram, exiting the cerebellum or Slide 4 are neurogenesis, during which cell division occurs to generate neurons; cell migration, when young neurons migrate away from the ventricular zone; axonogenesis, when the neuron starts to develop contact with their target neurons or other structures; cell death or pruning, when regressive events often occur, leading to the formation of the mature neuron. Transcripts by 3Playmedia Week 1 © King’s College London 2019 1.  Slide 5 Radial glial cells are elongated cells with a long process or endfoot on each surface. These are the progenitor cells of the nervous system. Radial glial cells undergo cell divisions repeatedly to expand the progenitor cell population, and some of these divisions give rise to a neuron shown by the shaded cell in the cartoon. The cell divisions extension of an axon. Slide 6 spinal cord, in which progenitors of cells migrate radially from the inside to the outside of the neural tube to generate neurons. This type of radial migration also occurs in the telencephalon, or forebrain, and is shown here in a transverse section of the developing telencephalon in a mouse, which will later form the cerebral hemispheres. Cells which migrate radially, along radial glia, give rise predominantly to The other type of migration which occurs in the telencephalon is called a tangential migration, in which neurons migrate orthogonal to the radial axis. Neuronal progenitors migrate from the ventral telencephalon into the dorsal telencephalon, the developing cerebral cortex, and intermingle with the neurons which have undergone radial migrations. These neurons, which have migrated tangentially, give rise to neurons with short axons, which use the neurotransmitter GABA, called inhibitory interneurons. neurulation is underway. These are the neural crest cells. Shown in a transverse section of the developing spinal cord, neural crest cells migrate away from the forming neural tube to form elements of the peripheral nervous system. In particular, these are the dorsal root ganglia and Slide 7 process of axonogenesis can be beautifully visualised in hippocampal neurons growing in vitro, as axonogenesis and neural development at the single cell level. several neurites, or processes. At Stage 3, one of these neurites becomes selected as an axon in a At Stage 4, the axon continues to grow and the dendrites start to grow out from the cell body. At Stage 5, the dendritic tree becomes more elaborate with small protrusions, or dendritic spines, Transcripts by 3Playmedia Week 1 © King’s College London 2019 2.  Slide 8 Development of the axon and the dendrites proceed in parallel. Growing axons are guided by synapses, these are most frequently made on dendrites, and in fact, the dendritic spines. neuron to the left on the neuron on the right. Thus, the neuron to the left is the presynaptic part, and the neuron to the right, the postsynaptic part. Slide 9 presynaptic axon and the postsynaptic dendrite, soma, or axon. There are many stages to synaptogenesis. Various molecules, including cell adhesion molecules, neurexins are families of transmembrane proteins that are expressed by the postsynaptic and the presynaptic neuron, respectively, and that are important in the process of synaptogenesis. They bind cluster together to form the synapse. help to consolidate synapse formation. The neurexins and neuroligins then help to recruit specialised groups of proteins into the presynaptic active zones, containing the neurotransmitter vesicles in the presynaptic terminal. and coordinated process. Slide 10 The nervous system forms not only by growth and elaboration of axons and dendrites, but also by sculpting of neuronal architecture and by cell death. Cell death is a surprisingly common phenomenon in the nervous system. It’s estimated that around 50 per cent of motor neurons, for example, die during later development. These regressive events may thus involve either the elimination of whole cells, or parts of cells, axons, synapses, or dendrites. In the examples shown of the developing cortex from humans, the complexity of the brain can initially be seen to increase, in terms of the density and numbers of neurons, up to two years of age, with increasing synapse formation. and some decrease in the complexity of the brain landscape occurs. Pruning can occur to axons and to dendrites, which disintegrate and the debris is then cleared away. Cell death and pruning may ensure that synaptic transmission and circuit function is optimised. It’s not completely clear why these events occur, but it may be to ensure that there are matching improved. Transcripts by 3Playmedia Week 1 © King’s College London 2019 3.  Module: Biological foundations of mental health Week 1 Introduction to brain anatomy Topic 1 Overview of CNS development - Part 1 of 3 Professor Sarah Guthrie Professor of of Developmental Neurobiology Lecture transcript Slide 2 Neural Development. We can think of neural development as taking place on two levels, namely, a ‘systems’ level and a shape that occur during the embryonic development of the nervous system. This process is called morphogenesis. Next, we will describe changes at the cellular level that allow cells to change from dividing progenitors into mature neurons with complex morphologies, interconnected in circuits. This process is called developmental events, with examples. Slide 3 Levels of Neural Development. In humans, development begins with fertilisation of the egg, which cleaves to give rise to a ball of cells week. And further development generates a two-layered embryonic disc, consisting of hypoblast and an epiblast. At the end of the second week, the process of gastrulation transforms this disc into a three-layered structure consisting of three so-called ‘germ’ layers-- the ectoderm, mesoderm, and endoderm-- which give rise to all the tissues of the body. Slide 4 By the end of the third week, the process of neurulation begins, which creates the embryonic some of the embryonic structures that will be present in the adult, such as the limb buds, which grow into the limbs. This stage is often called the ‘tailbud’ stage. In humans, the second month of gestation is referred to as the embryonic period, during which the major organ systems start to form. And months three to nine is the foetal period, which is mainly concerned with growth. Large amounts of cell proliferation take place, a process which is particularly important for the brain. Slide 5 Further development of the nervous system involves the ectoderm, which develops under the Transcripts by 3Playmedia Week 1 © King’s College London 2019 1.  process, a portion of the ectodermal germ layer is induced to become neural tissue, which will form the nervous system. As the tissue becomes neural, it also undergoes morphogenetic changes in shape, called neurulation. Slide 6 We will now look at neurulation in more detail, visualising the process of neurulation in a surface view, a transverse view, and in scanning electron micrographs of a human embryo. Early neurulation, at three weeks. The surface view is shown with the anterior, or cranial, end of the embryo at the top of the picture and the posterior, or caudal, end at the bottom of the picture. The arrow shows the level of the surface view at which the transverse section is taken. In the transverse section, at 19 and 20 days, we can see that the embryo consists of three germ layers. The ectoderm lies on top, and the medial part will give rise to the nervous system, with the more lateral regions giving rise to the epidermis of the skin. The medial part forms the neural plate, which has started to thicken. Underneath it lies the mesoderm, consisting of the notochord, medially, and two other blocks of mesoderm, laterally. Underneath this lies the endoderm. We can see that between 19 and 20 days, the neural folds rise up on either side of the midline and form a v-shape. Somites form from some of the mesoderm underneath these folds, which will later form the axial muscles. In the surface view, the somites can also be seen to form small blocks of tissue, and the embryonic disc to lengthen further. In the surface view, we can see how the neural In the scanning electron micrograph of the human embryo, the neural tube looks somewhat striated because of the somite blocks beneath it. Slide 7 can be seen to approach each other, and the somites to have expanded. Eventually, the neural tube closes and becomes enclosed and separated from the layer of ectoderm which forms over the top. In the surface view, it is clear that one region of the neural tube has started to fuse. This is typically anterior and the posterior ends, and the nervous system starts to be subdivided, with the spinal cord posteriorly, and the brain vesicles, or subdivisions, more anteriorly. The scanning electron micrograph of the human embryo is very similar to the diagram, but the embryo is attached to extra embryonic membranes which will later cover it. Slide 8 occurred, arching the body to give it what has sometimes been referred to as a ‘comma’ shape. Lateral folding has also occurred to enclose all forming internal organs in a covering of ectoderm, which will become the skin. We can see that the embryo has acquired a more recognisable appearance, with a head and tail somite blocks, and structures called branchial, or pharyngeal, arches, which will form elements of the lower jaw and neck. At a later stage of human development shown, you can also see the limb buds, outpocketings of tissue which will eventually grow into the limbs. The diagram highlights the developing eye, and the otic vesicle, which will give rise to the inner ear. In this way, the major structures of the developing Transcripts by 3Playmedia Week 1 © King’s College London 2019 2.  Slide 9 Surprisingly, the embryo of a human looks extremely similar to that of other animal groups at this stage. These beautiful drawings by the 19th century embryologist, Haeckel, show that at the tailbud stage, all the essential features of the body plan are present and look similar, even though the order to understand more about human development. Slide 10 Looking now at the further development of the neural tube without the other tissues, we can see that the cranial to caudal folding of the tube has taken place in concert with the folding of the rest of the embryo. Several subdivisions now appear in the tube. Whereas the region of the developing spinal cord remains with a small diameter, the forebrain, midbrain, and hindbrain, also termed the prosencephalon, mesencephalon, and rhombencephalon, have started to expand. The prosencephalon is divided into the telencephalon more cranially, and the diencephalon more caudally. The telencephalon is later destined to give rise to most of the cerebral hemispheres via an extensive folding process. The diencephalon will give rise to some of the important collections of neurons, such as the thalamus. These sorts of collections of neurons are termed nuclei. means that the cranial part of the hindbrain, called the pons, becomes separated from the more caudal region, the medulla. Transcripts by 3Playmedia Week 1 © King’s College London 2019 3.  12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr John Pizzey Topic 2 Week 1: Neuroanatomy, neural systems and brain function Introduction to brain anatomy Part 1 of 3 Learning aims By the end of the lecture, you should be able to: 1. Describe the main systems used to describe the - organisation of the nervous system - 2. Recognise the anatomical sub-divisions of the - nervous system - 3. Appreciate the mechanisms - that contribute to the complex internal circuitry of the brain - Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 2 of 10 1  12/09/2018 Introduction We have approximately 100 billion neurons in our brains…. with about 100,000 trillion synapses This is only part of the story in why the nervous system has such massive computing potential… Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 3 of 10 The basis of neural networks Convergence When many pre-synaptic neurons Sig e converge on any single post-synaptic neuron Recieving input from untiple Sanze Figure 1: Convergence Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 4 of 10 2  12/09/2018 The basis of neural networks oh Ability cell Divergence I single to project Axons of most pre-synaptic neurons to multiple divide into many branches that diverge to Number! end on many post-synaptic neurons - Figure 2: Divergence Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 5 of 10 Neural networks T As a result of convergence and divergence there are multiple ways of getting from one cell to another. & Different cells will be excited according to the route chosen - Different neural consequences Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 6 of 10 3  12/09/2018 mounibilities of Multiple routes * rading How many different ways from Bayswater to Arsenal? thoughthes Arsenal Brain aboutin world. Bayswater Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 7 of 10 Functional divisions of the nervous system General Organisation of the Nervous System The Nervous System -i - Central Nervous Peripheral System Nervous System 5 Brain Somatic Autonomic Cont Spinal Cord Sensory Parasympathetic Motor Sympathetic Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 8 of 10 4  12/09/2018 in dilfent work opposite was The autonomic nervous system - M a an D ⑧ Brin · Figure 3: The autonomic nervous system - Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 9 of 10 CNS or PNS? - Organisation of the Nervous System A better definition would be: C If a neuron is entirely contained within the brain and/or spinal cord, it is a CNS neuron. If any part of it (dendrites, axon or cell ↳ body) projects outside of these structures, it is a PNS neuron. Figure 4: The Central Nervous System (CNS) Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 10 of 10 5  12/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr John Pizzey Topic 2 Week 1: Neuroanatomy, neural systems and brain function Introduction to brain anatomy Part 2 of 3 · Doubleeitart i Anatomical divisions of the nervous system (1) Axes and planes - Crama · in Figure 5: Axes and planes I Figure 6: Axes and planes II Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 2 of 12 1  12/09/2018 Anatomical divisions of the nervous system (2) The central nervous system can also be divided into anatomical compartments Forebrain Midbrain Pons - Cerebellum - Hindbrain Medulla - Figure 7: Central nervous system divided into anatomical compartments Spinal cord Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 3 of 12 -seriousinformation The Spinal Cord - Spinal nerves are “mixed” nerves Motor & madee - - Figure 8: Spinal Nerves Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 4 of 12 2  12/09/2018 Spinal nerves There are normally 31 spinal nerves (8- cervical, - 12 thoracic, --- 5 lumbar, 5 sacral · and 1-coccygeal). All leave through a corresponding intervertebral foramen BUT the spinal cord ends at (4 vertebral level L1/L2.. Therefore … the cauda imp equina (horse’s tail). Figure 9: Spinal Nerves I Figure 10: Spinal Nerves II Cheri Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 5 of 12 chard todin a as bigatvertical fridHexanth - The Brainstem (1) Olderpart of brain so Medulla controls life supporting centers Bain Pons Hindbrain Cerebellum Medulla Figure 12: Sagittal section of the brain Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 6 of 12 3  12/09/2018 The Brainstem (2) Midbrain relays information between the forebrain and the hindbrain - Midbrain = [ Hindbrain Figure 13: Sagittal section of the brain Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 7 of 12 The Brainstem (3) Thalamus, part of the diencephalon, relays ascending sensory and descending motor information S - imp - => ste Thalamus very ! Relay Brainstem Figure 14: Sagittal section of the brain Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 8 of 12 4  12/09/2018 Brainstem Functions part of Brain. most impo & Conduit for ascending and descending pathways - & Conduit for cerebellar connections - S Houses most cranial nerve nuclei S Chemoreception, salivation, mastication, swallowing S Reticular formation – arousal; cardiovascular and - respiratory centres – vital life-supporting role Raphe, locus coeruleus nuclei - mood, sleep - - Substantia nigra – movement control adrelive Cdopamineyic Figure 15: Brain stem neurotransmitten as afBein neuver Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 9 of 12 The Forebrain Sulci, Gyri and Fissures The outer part of the - cerebrum is the cerebral cortex. It is thrown into several ridges (gyri, sing. gyrus) and grooves (sulci, sing. sulcus). - - Deeper grooves are known as fissures. The gyri and sulci of the # cerebral cortex increase the surface area of the brain to approx. 2,500 cm2 - this is Figure 16: Lateral aspect of the cerebral about the same as 4 pieces of A4 paper and allows hemisphere showing major gyri and sulci much more neural material to be contained within the skull. Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 10 of 12 5  12/09/2018 The cerebrum is divided into lobes - Some functions are particularly No function is only located to just one lobe BUT associated with individual lobes No lobe is associated with just one function - Sensory Cortex Motor Cortex - - Parietal Lobe Frontal Lobe Occipital Lobe Temporal Lobe Figure 17: Lobes of the brain Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 11 of 12 # The Forebrain - Parts neuroscience. of ad in finishe Cerebral Hemisphere Cerebral cortex a grouode Basal ganglia - Various small nuclei Olfactory bulb Diencephalon & Thalamus &Subthalamus Hypothalamus [ Epithalamus - Figure 18: Parts of the forebrain Week 1 Introduction to brain anatomy Topic 2: Neuroanatomy, neural systems andWeek brain2function – Lorem ipsum 12 of 12 6  13/09/2018 INSTITUTE OF PSYCHIATRY, PSYCHOLOGY & NEUROSCIENCE Module: Biological foundations of mental health Dr John Pizzey Topic 2 Week 1: Neuroanatomy, neural systems and brain function Introduction to brain anatomy Part 3 of 3 Connectivity (1) CORTICAL CONNECTIONS There are extensive connections to, from and within the cortex of the forebrain Ascending connections: Somatosensory from the thalamus: - (inputs from spinal cord via thalamic nuclei) - Auditory: - from the thalamus (inputs from the cochlea via thalamic nuclei) - Visual: - from the thalamus (inputs from the retina via thalamic nuclei) - Smell (direct into the olfactory cortex) - aly Sense I though thatams-- Taste (inputs from taste buds via thalamic nuclei) - Complex information from the cerebellum and basal ganglia via thalamic nuclei - Week 1 Introduction to brain anatomy Topic 2: Neuroanatom