Cells of the Nervous System - PM132 Lecture 10 PDF

PM132- Cell Biology Cells of the nervous system Owain Howell Institute of Life Sciences 1 [email protected]  We will learn about… Central and peripheral nervous system (CNS & PNS) Neuron- form and function Glia...

PM132- Cell Biology Cells of the nervous system Owain Howell Institute of Life Sciences 1 [email protected]  We will learn about… Central and peripheral nervous system (CNS & PNS) Neuron- form and function Glial cells- astrocytes, ependyma, microglia and oligodendrocytes of the CNS and Schwann cells of the PNS  Organisation of the nervous system Central nervous system- brain and spinal cord Peripheral nervous system- connects the body to the brain and includes the enteric nervous system The nervous system is composed of specialised cells called (optional) neurons Youtube and glia. explainer: Divisions of the nervous system https://www.youtube.com/watch?v=65fNI Is the axon A, B or C? C= Axon A, B= Dendrites B A C  (b) (Impulse generating) or oligodendrocyte (a) Structure of a neuron, (b) large projection neurons of the cortex Neuron (nerve cell) >Large nucleus, prominent nucleolus >Huge demand for protein synthesis (high levels of transcription and translation) >Nissl substance is ER, which is darkly stained with a Nissl histological stain (see inset) >Much of this protein is packaged and transported along the cytoskeleton to distant points of the dendrite or the axon (optional) Viewing neurons under the microscope.. Paste these links into your browser to view Nissl- stained neurons with a virtual microscope. https://www.digitalscope.org/ViewerUI/?SlideId=ff0c55e4 -ec2c-4c93-b577-f6434c6916c9&ann=11100001101 ‘Section through the cerebellum of the brain prepared by routine H&E staining that stains basophilic structures in neurons such as the nucleolus and the rough endoplasmic reticulum dark purple and acidophilic structures such as cytoplasm and extracellular proteins pink. Another staining component, Luxol fast blue, stains myelin found in white matter tracts deep blue. The neurons can be found at the junction between the light and dark staining layers of the cerebellum. They are distinguished from other cell types due to their very large size and unique staining. Locate a large neuron where the pale cell nucleus and large, prominent nucleolus are in the plane of section. In the cytoplasm of the cell body, most of the dark, purple-staining densities represent rough endoplasmic reticulum’. Original resource link- https://histology.oit.duke.edu/MoleculesCells/Introduction/Introduction.html  Cerebellar disorders  Inherited or acquired conditions that cause ataxia (impaired muscle coordination), hypotonia (decreased muscle tone), dysarthria (slurring of speech), and other complications.  Spinocerebellar ataxias: Atrophy (shrinkage) of the cerebellum and neurodegeneration (including loss of purkinje cell neurons – red arrows). https://youtu.be/sQFZVxA lXM8  DENDRITES taper and branch extensively. Convey information to the neuron Can be spiny or smooth, can account for 90% of surface area of the neuron Proximal and distal organisation of receptors and ion channels important in determining how synaptic input affects neuron A purkinje cell of the cerebellum. Receives tens of thousands of contacts from axons of other neurons. The cell sums this mass of inputs to produce the sole output of the cerebellum (to coordinate & refine movement, for example)  Axon connects neuron to neuron (or muscle, gland etc.) Uniform in diameter. Short or v. long (1m !!) Cell body size reflected by axon length Branch points and end in a splay of branches Myelinated or non-myelinated (see below) Axon transport- energy dependent -slow (1mm/day) or fast (400+mm/ day) transport of proteins, synaptic vesicles, and mitochondria to and from the soma The neuronal cytoskeleton & axon transport Cytoskeleton is a network of fibers extending throughout the cytoplasm It organizes the cell’s structures and activities, anchoring many organelles It is composed of three types of molecular structures: – Microtubules – Microfilaments – Intermediate filaments (NEUROFILAMENTS) Proteins are not synthesised in the axon (no ribosomes) and must be transported from the cell soma Interrupted or deficient axon transport results in neurodegeneration and dementia (e.g. Alzheimer’s disease– see later) Axon transport Anterograde transport moves material from the soma to the axon terminal under the direction of kinesin proteins Retrograde transport moves material from the axon terminal to the soma by the action of dynein proteins  Defects in axonal transport happen very early in the course of Alzheimer’s disease In Alzheimer’s disease, defects in the Microtubule Associated Protein Tau leads to a decrease in the microtubule binding affinity of Tau, causing destabilisation (breakdown) of microtubules and disrupted axonal transport. Why might neurons Synapses transmit chemical signals between neurons  Myelination organises the axon to enable the transmission of action potentials by saltatory (discontinuous) conduction  Nodes of Ranvier are approximately 1 μm wide and expose the neuron membrane to the external environment (long stretches of the axonal membrane are ‘insulated’ from this environment).  These gaps are rich in Nav+ & Kv+ channels.  The action potential propagated by one node of Ranvier jumps to and is  The myelinating glia (oligodendrocytes and Schwann cells) Evolution of myelin sheath, ensures fast conduction by axons Majority of axons myelinated in perinatal period (just before & after birth) Myelination is vital for coordinated movement There is continued proliferation, differentiation and myelin re- modelling in adults (Myelin makes memories by Fields & Bukalo. Nat Neurosci 2020. https://www.nature.com/articles/s41593-020-0606-x?proof=t ) (CNS) (PNS) Astrocytes play a vital role in synaptic transmission >The most abundant glial cell. >Essential for the formation and maintenance of the synapse >Controls the chemical environment at the synaptic cleft (the gap between pre- and post-synapse) (A) Fluorescent astrocyte- note it’s complex morphology. (B) An electron micrograph with axon, dendrite and astrocyte process (contacting the pre- and post-synapse; scale bar= 250 nm). (C) Astrocytes are functionally linked to synapses. They sense synaptic activity and respond to it through releasing neuroactive molecules that can signal back to synapses. From Allen & Eroglu. Neuron 96 697-708 (2017). https://www.cell.com/neuron/fulltext/S0896-6273(17)30925-X  Astrocytes Star-shaped (stellate). Hugely complex morphology and function Broadly divided into Protoplasmic and Fibrous forms (which predominate in grey and white matter, respectively) and the radial glial cell. Define the brain micro-architecture Control extracellular K+ homeostasis Supply glutamine to maintain glutamatergic neurotransmission Control synaptogenesis and synaptic maintenance Partake in neurotransmission Control blood flow and provide neurons with metabolic support Astrocytes (green) blood vessels (white) Blood-Brain Barrier: A selective border between brain and Maintains a stable environment for normal neuronal functioning. Three barriers to cross (endothelium, basal lamina and astrocyte end-feet) Astrocyte ‘end-feet’ help to form the blood-brain barrier to ensure that only essential nutrients and chemical signals pass into the CNS Ependymal cells line the CSF-filled ventricles of the brain and spinal cord Ependymal cells range in shape from squamous to columnar and many are ciliated CSF (in blue) bathes the brain and spinal cord and is rich in nutrients and helps clear waste products. CSF is reabsorbed into the blood Specialised Ependymal cells form the Choroid Plexus, which is the source of CSF (CerebroSpinal Fluid) Movement of cilia helps to circulate the CSF around the ventricles and over the brain A lumbar puncture is performed by  Microglia- Defenders of the brain Transformation of morphology and function * Resident tissue macrophage of the CNS Distributed throughout CNS accounting for 15% of brain cells In the normal adult brain they present a highly ramified morphology (*) Primary defense of CNS - first cells to respond to injury or infection (video)  Activated microglia can turn good astrocytes ‘bad’ By producing inflammatory mediators, IL-1alpha, TNF, and the complement protein C1q, activated (inflammatory) microglia induce astrocytes with poor trophic and synaptic functions for neurons and thus become neurotoxic (bad). https://www.nature.com/articles/nature21029  We discussed.. Organisation of the CNS (signal integration) and PNS (communicate information between CNS and rest of the body) The neuron and its extensions: Dendrites, cell soma and single axon Glial cells: Oligodendrocytes & Schwann cells make myelin in the CNS and PNS, respectively. Astrocytes help create the correct environment for nerve cells. Ependymal cells line the ventricles and produce cerebrospinal fluid. Microglia are the macrophages of the CNS. References Golgi and Cajal: The neuron doctrine and the 100th anniversary of the 1906 Nobel Prize. Current Biology (2006). 16: 147-51. http://dx.doi.org/10.1016/j.cub.2006.02.053 Neuroscience: Exploring the Brain, Bear et al. Chapter 2 Human Anatomy & Physiology, Marieb and Hoehn. Chapter 11 Molecular Biology of the Cell, Alberts et al.