Irene Yu, class of 2019

Transcription

1 Irene Yu, class of 2019

2 Nerve Cells and Glia Overview What is the brain made of - types of cells What do neurons do; How are they specialized to do it? CONCEPTS communication via signalling changeability isolating the brain from rest of body Chris Cohan, Ph.D. Dept. of Pathology/Anat Sci University at Buffalo 2017

3 Objectives 1. Understand the function of the nervous system. 2. Describe the morphological features of nerve cells and their functions. 3. Describe the differences between pseudounipolar, bipolar, multipolar neurons. 4. Understand the structural and biochemical importance of myelin. 5. Describe the role of microtubules in neurons and the significance of tau. 6. Understand the role of schwann cells. 7. Describe the properties and importance of the blood brain barrier.

4 Functions of Nervous Systems A mechanism that allows organisms to respond to the external and internal world How Collect and Evaluate information to produce some action Changeability (plasticity) - learning cellular, synaptic, structural, behavioral It s built for change!

5 The Neuron Functional unit of nervous system Specialized for communication: receive and integrate information conduct this information to other places transfer information to other cells Cell body Dendrites Axon Synaptic Terminals

6 Dendrites specialized to receive information contain receptors for neurotransmitters may be one or many; Can be highly branched resembling a tree. 95% of neuron s total volume!

7 Dendrites axon Diversity of neuron shape determined by complexity of dendrites Task in integrating info

8 Contain ribosomes for protein synthesis local control of synapse Usually contain dendritic spines sites for synapses Compartmentalize synaptic activity Dendrites Spines are dynamic structures As sites for synapses, they control CNS connectivity. Electrical activity, neurotransmitters, genetics can alter their shape and number, which affects the ability to make or break connections. They provide a mechanism for neural circuits to change throughout life.

9 Cell Body Nucleus, Ribosomes, Golgi, Mitochondria, Lysosomes, Pigment Endoplasmic reticulum - RER extensive- aggregates known as Nissl Substance ion channels, neurotransmitter receptors Major role in protein synthesis for dendrites, axon, and terminal. Pathological changes: chromatolysis, inclusions, storage of lipids and misfolded proteins. distribution changes with damage

10 Axon conduct electrical signals from cell body to terminal. Axon hillock One axon emerges from cell body at axon hillock. Axons may have branches Vary in length from 10 microns to greater than 1 meter.

11 Axon Relative Size Cell body size of tennis ball would have dendritic tree that fills a room and an axon the size of a 1/2 inch garden hose about 1/2 mile long Axons and dendrites are extensive in their projections. They must be supported structurally and metabolically.

12 Axon large axons are covered by a myelin sheath extensive wrapping of glial cell membrane around the axon - speeds conduction by electrical insulation PNS: Schwann cells, CNS: oligodendrocytes many glial cells cover the axon along length the myelin sheath is interrupted at regular intervals at Nodes of Ranvier concentrated with ion channels myelin axon Nucleus and cytoplasm Cross-section of peripheral nerve. Wrabitz et al. J Cell Biology myelinated axons PNS

13 How Myelination Occurs

14 Axon Myelin sheath is critical for the normal conduction of action potentials. Conduction is impaired by diseases that attack and degrade myelin. Multiple Sclerosis

15 Myelin Myelin biochemistry plays a significant role in compacting membrane layers and NS function and disease. MYELIN contains sphingomyelin ceramide sphingomyelinase fatty acid sphingosine P choline and glycosphingolipid ceramide hydrolases saccharide 1. Degradative enzymes affected by genetic defects lipid storage diseases 2. Myelin proteins involved in membrane compacting Viral, genetic, immune disorders cause demyelination 3. Saccharide confers antigenicity Autoimmune diseases cause demyelination

16 Myelin Disorders Several days after recovering from an upper respiratory virus, a patient complains of general muscle weakness and is hospitalized because he has trouble breathing. Pathology shows demyelination in peripheral nerves.

17 Synaptic Terminal Synapse transmits electrical signal from the terminal to other cells. 1. Electrical - transmit signal by direct contact through gap junctions. 2. Chemical - release neurotransmitters contained in vesicles. Synaptic cleft= 20 nm used to synchronize activity Unidirectional in transmission Many organelles- mitochondria, smooth ER, vesicles support transmission Complex structure- 100s of proteins - So? modulation, but also negatives! Presynaptic Synaptic vesicles Voltage gated calcium channels Postsynaptic Receptors Transporters

18 Chemical Synapses Postsynaptic location usually on dendrites, but also on cell bodies and axons Dendrite covered with synapses many contacts

19 Synapses So, when we show this We really mean this

20 Synapses Why have them?? Why not just connect one neuron to another??

21 Chemical Synapses Has the remarkable property of changeability (plasticity). Previous activity (how circuit is used) alters 1) presynaptic - amount of transmitter released 2) postsynaptic - receptors on the dendrite Changes the strength of connections and basis for memory, learning, behavioral change

22 Neuronal Cytoskeleton Actin, Microtubules, Intermediate Filaments Structural skeleton for neuron Polymers formed from monomeric units. Assembly and disassembly are dynamic processes controlled by many molecules involved in neuron health and disease. Actin - anchors membrane molecules (ion channels, receptors) actin Microtubules- support the tubular structure of axons; mediate axonal transport. Assembly promoted by MAPs (eg tau). Intermediate filaments- regulate axon diameter.

23 Microtubules Length of the axon - metabolic support? Axon & terminal cannot rely on diffusion of proteins from cell body! Axonal transport of proteins and organelles occurs along microtubules at rates up to 400 mm/day. Axonal transport is bidirectional - transporting cargo from cell body to terminal and terminal to cell body Proteins are sorted to specific locations! neurotransmitter receptors Ô dendrites synaptic release proteins Ô terminals

24 Axonal Transport A protein synthesized in the cell body of a spinal motoneuron would take 2.5 days to reach its terminal in the foot (1 meter away). Terminals that are distant from the cell body are particularly sensitive to any degradative changes due to the amount of time necessary for communication with the cell body.

25 Neuronal Cytoskelton Defects in their assembly or related proteins = disease Microtubule defects: Dementias often involve abnormal microtubuleassociated proteins MAPs (eg tau-opathies). many neurodegenerative diseases involve defects in axonal transport - accumulation of organelles in axon. ALL are targets of toxins Consequence: neuron structure and their dynamic processes are degraded.

26 Types of Neurons Neuronal morphology is specialized for role in receiving, conducting, and transmitting information e.g. receive info from one or many cells, conduct action potential short or long distances Functional classes: sensory, motor, interneurons, projection CNS Pseudounipolar Bipolar PNS sensory- conduct over long distances skin Multipolar CNS- integrate inputs

27 Pathways Neuron pathways transmit and analyze information neuron 3 released from inhibition neuron 3 is inhibited neuron 3 is excited 1 2 3

28 Glial Cells Intimately related to neurons and their function; actively communicate with neurons Support neuronal structure neuronal metabolism neuronal growth/repair respond to injury

29 Peripheral NS Peripheral nerves are supported by collagen connective tissue (fibroblasts, collagen). Contain schwann cells surround cell bodies in ganglia surround axons - myelinating and nonmyelinating types Pathology/Duke Univ Schwann cells release growth factors that influence recovery from injury

30 Peripheral NS Fascicles of unmyelinated axons GM Khan et al, Neuroscience

31 CNS Glia The CNS lacks fibroblasts and connective tissue Contains oligodendrocytes astrocytes microglia ependymal cells Dr. Heffner will cover these.

32 CNS Glia - Astrocytes Types: protoplasmic, fibrous, radial glia Have long processes that give the cell the appearance of a star

33 CNS Glia - Astrocytes some processes terminate as endfeet on capillaries, nodes of Ranvier, and synapses - regulate the environment Functions: Remove excess K + Induce formation of + synapses Ensheath CNS synapses Remove neurotransmitters Participate in neuronal metabolism Secrete growth factors promote neuronal survival Guide neuronal migration; may provide stem cells Activated after CNS injury, release neurotoxins Create Blood Brain Barrier astrocyte blood vessel.

34 Blood Brain Barrier What is it Small ions, water soluble molecules, charged molecules, most proteins, most nonessential AA/fatty acids cannot enter CNS from blood vessels. Why Many molecules in blood are the same as the neurotransmitters used by neurons. Blood also contains molecules that are toxic to neurons. So the CNS must be protected.

35 Blood Brain Barrier What causes it sophisticated barrier formed by brain capillaries, pericytes, and astrocytes blocks diffusion of most molecules. Endothelial cells are joined by adherens and tight junctions. Tight junction btw brain endothelial cells are impermeable. Impermeability of junctions due to astrocyte end feet on capillaries. Pericyte Basal lamina Capillary Astrocyte end feet

36 Blood Brain Barrier Additional Properties contribute to barrier No fenestrated endothelial membrane What CAN enter the brain To enter brain, molecules must cross cell membranes lipid-soluble molecules carrier-mediated transport - essential AA/fatty acids, glucose, others drug delivery?

37 Blood Brain Barrier Pathological Conditions inflammation, infection, tumors, ischemia alter endothelial tight junctions and make the BBB leaky - Neurotoxic components in blood leak into CNS cause degeneration. Circumventricular Organs Regions with NO BBB Located in midline around 3 rd and 4 th ventricles Important sites of communication btw blood and brain glucose levels, appetitive molecules, osmolarity, toxins, neurosecretion

38 Blood Brain Barrier Decreased Immune Response white cells, complement, immunoglobulins are prevented from entry into CNS. Decreased resistance to infection Choroid plexus has Blood-CSF Barrier Endothelium and ependyma - only specific molecules pass from blood to CSF. Ependymal lining has NO barrier Molecules exchange freely between extracellular space and CSF.

39 Be Amazed by the Numbers The Brain contains: 100 billion nerve cells 1 trillion glial cells Axons/dendrites produce 300 million feet of wiring packed into a 1.5 quart space Each neuron receives , 000 synapses creating 100 trillion connections

40 These connections account for all functions of the brain including sensation, movement, language, reasoning, consciousness, and more. Where is the information that instructs neurons to make 100 trillion specific connections that allow the brain to function?