Med Phys Pharm 551 L17 Nerve Intro PDF

Lecture #17: Nervous System Organization & Function Julia Hum, PhD Primary Course Instructor Course Meets: Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm (317B or WebEx)  L17: Lear...

Lecture #17: Nervous System Organization & Function Julia Hum, PhD Primary Course Instructor Course Meets: Monday/Wednesday/Friday: 2:00-2:50pm Office Hours: Monday/Wednesday/Friday 11:00am-12:00pm (317B or WebEx)  L17: Learning Objectives 1. Classify the division/subdivisions of the nervous system and structure of neurons 2. How do action potentials occur in nerves and how do they propagate? 3. Differentiate what impacts neurons excitability and relate the changes in neuronal conduction to the disease state of MS 4. Categorize the classes of NT and identify the small-molecule neurotransmitters 5. Detail the main steps of NT formation and important enzymes 6. Draw and detail the process of neurotransmission – predict how changes could impact signaling 7. Identify the two main NT receptors and their downstream effects 8. Summarize how signal termination occurs and identify specific NT mechanism(s) of signal termination  L17: ”Take Home” Slide The ”Hows” of L17: How is the Nervous System organized? How do neurons receive and conduct signals? How can action potential propagation be affected? How does MS relate to neuron physiology? How do neurons act as integrators? How does neurotransmission occur? How is neurotransmission stopped?  Subdivisions of the Nervous System Central Nervous System (CNS) Brain and spinal cord The nervous system's integrative and decision-making arm Peripheral Nervous System (PNS) Somatic Division – carries information from the skin receptors to brain and from brain to the muscles Autonomic Division – regulates involuntary functions Sympathetic LO1 Gray’s Basic Anatomy, Moore et al. (2018) Parasympathetic  Nervous System Organization: Neurons Dendrites hillock Receive information (synapse) with other neurons Depolarize or hyperpolarize Cell body (soma) Contains nucleus and source of protein synthesis Axon hillock Contains voltage-gated Na+ channels that can generate APs LO1,2 Clinically Oriented Anatomy, Moore et al. (2018)  Neuron Classification by ! Morphology Y I F https://img.purch.com/w/660/aHR0cDovL3d3dy5saXZlc2NpZW5jZS5jb20vaW1hZ2VzL2kvMDAwLzEwMS81MDkvb3JpZ2luYWwvcm9zZWhpcG5ldXJvbi5qcGc=  How are messages sent/received? 2 Cell body 3 1 LO1 Clinically Oriented Anatomy, Moore et al. (2018)  I EW Action Potential: V RE Basic Steps & Terms Threshold Potential (Vth) – voltage needed to open the # of voltage-dependent Na+ channels to trigger an AP “All or nothing” – When Vm crosses the threshold voltage-gated Na+ channels open in mass As depolarization begins it won’t stop until “ionic flood” is finished Overshoot – often AP peak isn’t exactly at 0mV Usually cell becomes + charged compared to ECF Afterpotentials – AP’s are transient Downstroke – caused by voltage-dependent K+ channels LO2 K+ efflux leads to Vm repolarization  Nerve Action Potential Propagation Neuronal Signaling – Sequential Steps 1.Excitation 2.Initiation 3.Propagation 4.Recovery LO2,3 Lippincott’s Physiology (pg 21)  1. Neurons Excitability: Axon Diameter and Insulation Small Diameter Axons Distribution of Na+ and K+ channels along axon - APs propagated through opening of fast Na+ channels along membrane These characteristics result in relatively slow action potential LO2,3 conduction velocities (0.5 - 2.0  1. Neurons Excitability: Axon Diameter and Insulation Larger Diameter Axons Fast Na+ channels localized to nodes of Ranvier (1-2 μm spacing) APs propagated through opening of fast Na+ channels at nodes of Ranvier APs propagate from node-to- node - These characteristics result in LO2,3  Clinical Connection: Multiple Sclerosis Demyelinating disease of CNS neurons Unknown cause(s) Immune cells produce antibodies against one or more sheath components Myelin swells and degrades, and axonal conduction is interrupted Symptoms: tremors, visual disturbances, autonomic dysfunction, weakness, and fatigue Cure: none Treatments options available Disease usually progresses over a period of 10 to 20 years LO3 https://content.healthwise.net/resources/12.6/en-us/media/medical/hw/h9991221.jpg  2. Initiation and 3. Propagation Initiation – when receptor potential is big enough to cross Vth – a spike will be triggered Propagation – Driven by the electrochemical gradient for Na+, Na+ flows into a cell “Active current” LO2,3  4. Recovery Recovery – Na+ channels – inactivated via depolarization w/in milliseconds During recovery ion gradients are ”renormalized” by ion pumps LO2,3  Neurons Act as Integrators LO9  Postsynaptic Integration Incoming Messages Excitatory Postsynaptic Potential (EPSP) Rapid influx of Na+ AP begins in the initial segment of axon More Na+ channels located there Inhibitory Postsynaptic Potential (IPSP) Hyperpolarization – increase the degree of intracellular negativity Caused by increased permeability of K+ (efflux) or Cl- (influx) LO9  Spatial summation of postsynaptic potentials LO9  Spatial summation of postsynaptic potentials LO9  Temporal summation of postsynaptic potentials LO9  Neurotransmission – Summary Figure LO6  Neurotransmissi on – Textbook Figure LO6  Neurotransmitter Classes GABA3 most widely used NTs LO4  Synaptic Vesicles and Neurotransmitter Release Ca++ influx leads to a “Ca++-dependent secretory event” Ca++ binds synaptotagmin Leads to activation of SNARE complex SNARE complex Synaptobrevin http://www.nature.com/nrn/journal/v16/n1/images/nrn3875-i1.jpg Syntaxin SNAP-25 LO6  Tissue Specific Receptors LO7  What does the NT signal result in? LO8 Neurons -> Nerves What’s Next? Support Cells CNS Motor Control Diseases of Motor Control Clinically Oriented Anatomy, Moore et al. (20