4BBY1030 L6.pdf

IoPPN & FoLSM Dr Clemens Kiecker 4BBY1030 Cell Biology & Neuroscience Lecture 6 Neuroscience Education Neurons and glia Learning outcomes By the end of this lecture you should be able to: a) describe the major classes of neurons b) identify the structural characteristics of a prototypical neuron c)...

IoPPN & FoLSM Dr Clemens Kiecker 4BBY1030 Cell Biology & Neuroscience Lecture 6 Neuroscience Education Neurons and glia Learning outcomes By the end of this lecture you should be able to: a) describe the major classes of neurons b) identify the structural characteristics of a prototypical neuron c) understand the principles of convergence and divergence and how they can help to build neural networks d) describe the classes of glia in the PNS and CNS e) explain how the different functions of glia provide support to the nervous system Dr Clemens Kiecker Neurons and glia The nervous system… is the main controlling and communicating centre of the body coordinates and controls all essential bodily functions processes information from the environment and enables the body to respond accordingly provides us with higher functions such as memory, emotions and learning Dr Clemens Kiecker Neurons and glia Chapter 1 Neurons Dr Clemens Kiecker Neurons and glia 4 The ‘prototypical’ neuron Unidirectional flow of information Dr Clemens Kiecker Neurons and glia 5 Neurons are transcriptionally and translationally very active Very prominent nucleolus However, they are also postmitotic à diffuse chromatin Martinelli et al. (2003) Brain Res Bull Dr Clemens Kiecker Neurons and glia 6 The neuronal cytoskeleton Microtubules: a and b tubulin dimers à transport Neurofilaments: coiled-coil fibres à structural maintenance Microfilaments: actin dimers à structural maintenance, movement Dr Clemens Kiecker Neurons and glia 7 Axonal transport 50-250 mm/day aging mitochondria, endocytotic vesicles Dr Clemens Kiecker Neurons and glia 100-400 mm/day mitochondria, neurotransmitter vesicles 8 Many axons are myelinated by specialised glial cells De-myelination in multiple sclerosis Auto-immune disease of unknown aetiology UK 1:1000 Genetic and environmental factors node of Ranvier Dr Clemens Kiecker Neurons and glia 9 Myelination speeds up nerve conduction = saltatory conduction Dr Clemens Kiecker Neurons and glia 10 Coverings of peripheral nerves Endoneurium Delicate connective tissue layer surrounding axon and associated Schwann cells Perineurium Connective tissue layer surrounding groups of axons forming fascicles Epineurium Robust connective tissue layer Surrounding individual fascicles, contains blood vessels and forms the nerve itself Dr Clemens Kiecker Neurons and glia 11 Coverings of peripheral nerves Nissl staining: basic dyes (e.g. cresyl violet) à stains cell body, in particular ER Nissl substance: rER Chromatolysis: dissolution of Nissl substance in response to ischemia, axotomy, cell toxicity, infections etc. Dr Clemens Kiecker Neurons and glia 12 The foundations of modern neuroscience Dr Clemens Kiecker Neurons and glia 13 Classes of neurons Functional classification: Sensory/afferent neurons: Motor/efferent neurons: Interneurons: send signals towards the CNS send signals away from the CNS, into the periphery act locally, within the CNS, and connect neurons with each other Structural classification: Multipolar: Bipolar: (Pseudo)unipolar: Dr Clemens Kiecker most neurons in the CNS (e.g. motor neurons) e.g. sensory neurons in the retina neurons with a single process that often splits into a peripheral and a central branch (e.g. sensory neurons) Neurons and glia Classes of neurons Multipolar: e.g. motor neuron in the spinal cord Bipolar: rare, e.g. bipolar cells in the retina Pseudo-unipolar: e.g. primary somatosensory neuron in the DRG Unipolar: very rare in vertebrates but common in invertebrates Dr Clemens Kiecker Neurons and glia 15 Chapter 2 Connectivity Dr Clemens Kiecker Neurons and glia 16 Neurons connect via synapses Electrical synapses (remember gap junctions) Chemical synapses: convert electrical signal à chemical signal à electrical signal Synapses can be axo-dendritic axo-somatic axo-axonic Dr Clemens Kiecker Neurons and glia 17 Synapses under the electron microscope Neurotransmitter vesicles in the pre-synapse Post-synaptic density (PSD) Many axo-dendritic synapses form at dendritic spines Dr Clemens Kiecker Neurons and glia 18 Convergence and divergence Neurons can receive inputs from tens of thousands of other neurons, but they can only make a binary decision: to fire and action potential or not Dr Clemens Kiecker Neurons and glia 19 Multiple routes (e.g. from Bayswater to Arsenal) Dr Clemens Kiecker Neurons and glia 20 Chapter 3 (Neuro-)Glia Dr Clemens Kiecker Neurons and glia 21 Major classes of neuroglial cells Dr Clemens Kiecker Neurons and glia 22 Fibrous and protoplasmic astrocytes Fibrous astrocytes: white matter, support axons Protoplasmic astrocytes: grey matter, homeostatic and other roles Dr Clemens Kiecker Neurons and glia 23 Roles of astrocytes Structural support Extracellular electrolyte homeostasis (ions, water, pH) Energy storage (glycogen, glucose, lactate) Effects on endothelial cells and angiogenic factors à Blood-Brain-Barrier regulation Glia limitans Uptake and regulation of neurotransmitters Glutamate regulation (glutamate/glutamine transport) Neurotrophic factors à neuronal survival, myelination Neurogenesis and synaptogenesis through modification of the ECM Inhibition of axon regeneration Immune modulation (together with microglia) Dr Clemens Kiecker Neurons and glia 24 Oligodendrocytes A single oligodendrocyte (green in the fluorescent image on the right) can myelinate multiple different axons (red) Oligodendrocytes inhibit axon regeneration in the CNS (together with astrocytes) Dr Clemens Kiecker Neurons and glia 25 Microglia Immune defence and removal of cellular debris in the brain Pro-inflammatory Once activated, they retract their processes and become phagocytotic Dr Clemens Kiecker Neurons and glia 26 Ependymal cells Found in the lining of the ventricular system and spinal canal Secrete, monitor and aid in the circulation of cerebro-spinal fluid ß Ependymocytes: cilia and microvilli VandenBergh et al. ß Choroid plexus: specialized cuboidal epithelium in all ventricles; secretes cerebro-spinal fluid Dr Clemens Kiecker Neurons and glia 27 Glia in the peripheral nervous system Schwann cells Myelination of PNS axons (one Schwann cell per axon) Rapid removal of myelin debris by phagocytosis Promote axon regeneration by producing permissive ECM components (e.g. laminin) and neurotrophins (e.g. NGF) Satellite cells Structural and metabolic support (similar to astrocytes in the CNS) Dr Clemens Kiecker Neurons and glia 28 Recommended reading Bear, Connors, Paradiso (2016) Neuroscience: Exploring the Brain. 4th ed. Wolters Kluwer. There is an entire scientific journal called Glia! Dr Clemens Kiecker Neurons and glia 29 Thank you for your attention [email protected] © King’s College London. All rights reserved