Lecture - Cells of the NS - Synaptic Transmission - 19Nov2024 PDF

Cells of the Nervous System Synaptic Transmission Dr Vassilis Beglopoulos Slides by Dr Philip Welsby 1 Nervous system lectures Tuesday 19 November Cells of the nervous system / Synaptic transmission Wednesday 20 November Membrane...

Cells of the Nervous System Synaptic Transmission Dr Vassilis Beglopoulos Slides by Dr Philip Welsby 1 Nervous system lectures Tuesday 19 November Cells of the nervous system / Synaptic transmission Wednesday 20 November Membrane potentials / Action potentials Tuesday 26 November Autonomic nervous system Wednesday 27 November Graded potentials / Neuromuscular junction / Recap exercises 2 Lecture Content - 1 hour st  Introduction to neurons and basic neuroanatomy  Introduction to non-neuronal cells of the nervous system SUGGESTED READING  Silverthorn, Human Physiology: An Integrated Approach, 7 th ed., Parts of Chapters 5, 8 & 11  Rang et al., Rang and Dales Pharmacology, 8th ed., Parts of Chapters 4, 12, 13 & 14 3 Organisation of the NS  Central nervous system (CNS) ◦ Brain & spinal cord  Peripheral nervous system (PNS) ◦ Nerves outside the CNS ◦ Nerves extending to & from the brain and spinal cord 4 Functions of the Nervous System 1. Sensory ◦ Afferent neurons transmit sensory information  Information travels from the periphery to the CNS 2. Processing ◦ CNS processes incoming sensory information & responds  Initiates response that modifies a process 3. Motor ◦ Efferent neurons transmit motor signals  Information travels from CNS to periphery 5 Sensory & Motor Information Types 6 The Neuron  Functional unit of the nervous system ◦ Estimated that the human brain contains 86 billion neurons  Longevity ◦ Can live and function for a lifetime  Do not divide ◦ Foetal neurons lose their ability to undergo mitosis ◦ Neural stem cells are an exception  High metabolic rate ◦ Require abundant oxygen and glucose Neuron of the Hippocampus 7 http://jcb.rupress.org/content/190/3/282/F3.large.jpg The Neuron  Cell body: ◦ Most neuronal cell bodies located within the CNS  Protected by bones of the skull and vertebral column ◦ Ganglia – clusters of cell bodies in PNS ◦ Contains nucleus, organelles plus other structures  Chromatophilic bodies (Nissl bodies)  Clusters of rough ER and ribosomes 8 The Neuron  Dendrites: ◦ Extensive branching from the cell body ◦ Transmit electrical signals toward the cell body  Axons (nerve fibre): ◦ Each neuron has only one, but it can branch ◦ Impulse generator and conductor  Transmits action potentials away from cell body 9 The Neuron 10 Sensory & Motor Information Types 11  12 http://www.nig.ac.jp/section/emoto/emoto-e.html Neuron Classes 13 Neuron Classes  Pseudounipolar neuron: ◦ Single axon  Branches to connect to spinal cord or CNS neurons  Dendrites are where it receives input – i.e. Senses  E.g. Receptors for touch, heat etc.  Chemically gated ion channels ◦ Found as:  Sensory neurons http://www.highlands.edu/academics/divisions/scipe/biol ogy/faculty/harnden/2121/notes/nervous.htm 14 Neuron Classes  Bipolar neuron: ◦ Single dendrite ◦ Single axon ◦ Rare – found as:  Sensory neurons in ear, eye and nose http://www.highlands.edu/academics/divisions/scipe/biol 15 ogy/faculty/harnden/2121/notes/nervous.htm  16 http://webvision.med.utah.edu/2011/04/seminars-rachel-wong-ph-d-developmental-strategies-underlying-the-wiring-patterns-of-retinal-neurons/ Neuron Classes  Multipolar neuron: http://brain.utah.edu/_images/olm.gif ◦ Single axon  Myelinated – nerve fibre ◦ Multiple dendrites  Multiple inputs summate to generate an action potential ◦ Found as:  Interneurons – mostly found within CNS  Motor neurons http://www.highlands.edu/academics/divisions/scipe/biol 17 ogy/faculty/harnden/2121/notes/nervous.htm Glial Cells  Commonly described as support cells of the nervous system  6 types: ◦ Neuroglial cells in the CNS: 1. Astrocytes – chemical environment 2. Microglia - phagocytic 3. Ependymal - CSF 4. Oligodendrocytes - myelin ◦ Non-neuroglial cells found in the PNS: 1. Schwann cells - myelin 2. Satellite cells – chemical environment 18 http://www.ninds.nih.gov/disorders/brain_basics/ninds_neuron.htm Glial Cells 19 Schwann Cells  Produce the myelin sheath in the PNS 1. Protects & insulates axons  Myelinated nerves conduct AP’s more rapidly 2. Maintains microenvironment 3. Assist neuronal repair 4. Enables saltatory conduction ◦ Note:  White matter – myelin  Grey matter – cell bodies & dendrites http://upload.wikimedia.org/wikipedia/commons/6/64 /Coronal_cross-section_of_human_brain.jpg 20  21 http://synapses.clm.utexas.edu/atlas/5-3.bmp Summary - 1 hour st  Neurons have common structural feature but can be classified based on anatomical features  Nervous system contains additional non-neuronal cells with diverse functions 22 Lecture Content - 2 nd hour  Introduction to electrical synapses  Introduction to chemical synaptic transmission SUGGESTED READING  Silverthorn, Human Physiology: An Integrated Approach, 7th ed., Parts of Chapters 5, 8 & 11  Rang et al., Rang and Dales Pharmacology, 8th ed., Parts of Chapters 4, 12, 13 & 14 23 The Neuron 24  The Synapse  Synapse- connection between a neuron and a second cell ◦ E.g. from presynaptic to postsynaptic neuron  Form of signal: 1. Electrical synapses  E.g. In smooth muscle and heart – gap junctions 2. Chemical synapses  Release of neurotransmitters (chemicals)  Signal transmission is one-way 25 The Electrical Synapse  Direct transfer of ionic current from one cell to the next  Gap junction ◦ The membranes of two cells are held together by clusters of connexins  Connexon ◦ A channel formed by six connexins  Two connexons combine to from a gap junction channel ◦ Allows ions to pass from one cell to the other ◦ 1-2 nm wide  Large enough for all the major cellular ions and many small organic molecules 26 The Electrical Synapse 27 Bear et al., Neuroscience Exploring the Brain, 3 rd ed  EM Gap Junction Image Left – internal view where proteins look like little doughnuts Middle – external view where region looks like aggregated lumps Right – side view showing plasma membrane of two cells Bloom and Fawcett, A Textbook of Histology, Chapman and Hall, N.Y., Twelfth Edition, 1994, 28 Figure 2-14 The Electrical Synapse  Cells connected by gap junctions are said to be “electrically coupled” ◦ Flow of ions from cytoplasm to cytoplasm bidirectional ◦ Very fast, fail-safe transmission ◦ Almost simultaneous action potential generations  Cells using gap junctions: ◦ Skin epithelium ◦ GI epithelium ◦ Smooth Muscle ◦ Cardiac Muscle  Often found where normal function requires that the neighbouring cells be highly synchronized 29 The Chemical Synapse  Synaptic cleft: 20-50 nm wide (gap junctions: 3.5 nm) ◦ Adhere to each other by the help of a matrix of fibrous extracellular proteins in the synaptic cleft  Presynaptic density (= axon terminal) contains: ◦ Synaptic vesicles – amino acids & amines ◦ Secretory granules (~100nm) – peptides 30  31 http://blog.nervousencounter.com/?p=215 Neurotransmitters  What is a neurotransmitter? ◦ Substance released by a neuron to affect transmission of information to a postsynaptic target  Neuron requires: 1. Method of synthesis  Usually in the nerve terminal 2. Storage system 3. Mechanism of release 4. Pre or postsynaptic target  Binding should elicit a response 5. Mechanism of removal 32 http://www.ajnr.org/content/22/10/1813/F4.expansion.html Neurotransmitters  What else is needed? 6. Nerve stimulation must result in release of enough transmitter to elicit the response observed 7. When applied exogenously, the response should be mimicked 8. Antagonists should block both the endogenous and exogenous transmitter 33 Neurotransmitter Classes 34 Neurotransmitters  Major Neurotransmitters: ◦ Within the CNS:  Glutamate – principle excitatory neurotransmitter of CNS  GABA – principle inhibitory neurotransmitter of CNS ◦ Both CNS & PNS  Acetylcholine  Principle neurotransmitter of the parasympathetic nervous system  Critical neurotransmitter for memory formation  Noradrenaline  Principle neurotransmitter of the sympathetic nervous system 35 The Chemical Synapse  Neurotransmitter Release ◦ Exocytosis: Process by which vesicles release their contents 36 Bear et al., Neuroscience Exploring the Brain, 3 rd ed  37 http://www.intechopen.com/source/html/37703/media/image3.jpeg  The Chemical Synapse  Basic steps 1. Neurotransmitter synthesis 2. Neurotransmitter loaded into synaptic vesicles 3. Action potential causes membrane depolarization 4. Voltage gated calcium channels open  Ca2+ concentration rises from 0.0001mM to 0.1mM  Ca2+ triggers fusion of synaptic vesicles to presynaptic terminal  Very rapid – 0.2msec – Ca2+ enters exactly where needed 5. Neurotransmitter released into synaptic cleft by exocytosis 6. Neurotransmitter crosses cleft and binds to postsynaptic receptors 7. Biochemical/electrical response elicited in postsynaptic cell 8. Neurotransmitter removed 38 The Chemical Synapse  Neurotransmitter recovery and degradation ◦ Diffusion: Away from the synapse ◦ Reuptake: Neurotransmitter re-enters presynaptic axon terminal  E.g. NAT – noradrenaline transporter (also NET) ◦ Enzymatic degradation: inside terminal cytosol or synaptic cleft  E.g. AChE cleaves Ach to inactive state 39 http://www.scientificcomputing.com/sites/scientificcomputing.com/files/05_K_Boyle_Hippocampal_Neuron.jpg 40 The Chemical Synapse Postsynaptic Target Receptors  Ionotropic: ligand-gated ion channels ◦ Ligand binding causes a small conformational change that leads to the opening of channels  Not as selective to ions as voltage-gated channels ◦ Depending on the ions that can pass through, channels are either excitatory or inhibitory 41 Bear et al., Neuroscience Exploring the Brain, 3 rd ed The Chemical Synapse Neurotransmitter Target Receptors  Metabotropic: GPCRs ◦ Trigger slower, often longer-lasting actions ◦ Metabotropic receptors also presynaptic  Neurotransmitter may activate both ionotropic & metabotropic receptors  E.g. Glutamate – 16 ionotropic and 8 metabotropic receptors 42 Bear et al., Neuroscience Exploring the Brain, 3 rd ed Summary - 2nd hour  Be able to describe: ◦ Basic structure and function of electrical synapses ◦ Structure and function of chemical synapses  Neurotransmitter synthesis, storage, release, signal generation, and removal 43