Psych 261 Lecture 4 Jan 15 2025 PDF
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University of Waterloo
2025
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This document is a lecture on neuroscience, specifically focusing on action potentials and various aspects of the nervous system. It covers topics such as the all-or-none law, the propagation of action potentials, and different kinds of neurotransmitters. This material provides a foundation for understanding the functioning of the nervous system in health and disease.
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Absolute Refractory Relative Refractory Period Period +40 Voltage (mV) 0 -70 0 1...
Absolute Refractory Relative Refractory Period Period +40 Voltage (mV) 0 -70 0 1 2 3 Time (ms) Varieties of Action Potentials Bean, B. P. (2007). The action potential in mammalian central neurons. Nature Reviews Neuroscience, 8(6), 451-465. Figure 1b & 1c, p. 453. The all-or-none law: The magnitude of the action potential remains the same regardless of the strength of stimulation. +4 +4 0 0 Voltage (mV) Voltage (mV) 0 0 -7 -7 0 0 Tim Tim e e Weak Stimulus Strong Stimulus Interesting Observations + Membrane Voltage - + Temperature - + Volume - Tim e For a review see: Pollack, G. H. (2001). Cells, gels and the engines of life: a new, unifying approach to cell function (p. 305). Seattle, WA: Ebner & Sons. Propagation of the Action Potential The action potential is regenerated at adjacent regions of the axon, which results in its movement down the axon. Passive and Saltatory Conduction Few Na+ channels Multiple Sclerosis: An Autoimmune Disorder Stage 1 Symptoms are intermittent Muscle Weakness Sensory Problems Cognitive Deficits Stage 2 Symptoms get progressively worse Brain lesion associated with multiple sclerosis characterized by a loss of myelin. Shiee, N., Bazin, P. L., Ozturk, A., Reich, D. S., Calabresi, P. A., & Pham, D. L. (2010). A topology-preserving approach to the segmentation of brain images with multiple sclerosis lesions. NeuroImage, 49(2), 1524-1535. Multiple Sclerosis: Genetic Factors Higher prevalence of MS in people of European ancestry. There are numerous genetic variants associated with MS. Barrie, W., Yang, Y., Irving-Pease, E. K., Attfield, K. E., Scorrano, G., Jensen, L. T., … Willerslev, E. (2024). Elevated genetic risk for multiple sclerosis emerged in steppe pastoralist populations. Nature, 625(7994), 321–328. Figure 1a, p. 322. 2 Lymphocytes invade the the brain through a leaky blood-brain barrier Based on Mirza, A., & Mao-Draayer, Y. (2017). The gut microbiome and microbial translocation in multiple sclerosis. Clinical Immunology, 183, 213-224. Fig 1, p. 220 Blood Vessel Epithelium Blood Vessel Inflammatory Mediators Lymphocyte Blood-brain barrier Astrocyte 1 Blood-brain barrier becomes more porous Microglia Neuro n Lymphocytes and microglia release inflammatory 3 substances Brai n Oligodendrocyte Inflammatory substances break down myelin segments 4 Myelin segments are Damage to myelin exposes a The axon withers downstream intact on a healthy segment of axon which has very of the demyelinated section. neuron few ion channels. Axonal Ovoid Myelin Ion Channels Downstream of the demyelinated region the axon withers away and an axonal ovoid is formed. The action potential The action potential is Based on: Trapp, B.D., & Dutta R. (2011). Mechanisms of neuronal dysfunction and continues down the axon. disrupted. degeneration in multiple sclerosis. Progress in Neurobiology, 93, 1-12. Fig 1; Waxman, S. G. (2006). Axonal conduction and injury in multiple sclerosis: the role of sodium channels. Nature Reviews Neuroscience, 7(12), 932-941. Fig 1. p. 933. Demyelinated Axon (axon is coloured green) Myelinated Segment (myelin is coloured red) Axonal Demyelinated Axon Ovoid (axon is coloured green) Trapp, B.D., & Dutta R. (2011). Mechanisms of neuronal dysfunction and degeneration in multiple sclerosis. Progress in Neurobiology, 93, 1-12. Axonal demyelination Outcome 1: Remyelination of Outcome 2: New ion channels are Outcome 3: Healthy neurons take associated with Multiple the axon by oligodendrocytes inserted into the membrane allowing over the functions of the damaged Sclerosis. (possibly from NG2 cells) the action potential to continue. neuron. Healthy Neuron Weakening of the intestine wall 2 cased by stress, pathogens, dysbiosis Microbial 3 Lymphocytes invade the the inflammation etc. translocation 4 brain through a leaky blood- brain barrier Inflammatory Mediators Blood Vessel Lymphocyte Blood Vessel Epithelium Blood-brain Intestinal barrier Epithelium Astrocyte Mucus Lymphocyte Pro-inflammatory Microglia Bacteria Neuro Anti-inflammatory n Bacteria Intestin Brai 1 Dysbiosis e n Inflammatory substances break down myelin segments 5 Oligodendrocyte Based on Mirza, A., & Mao-Draayer, Y. (2017). The gut microbiome and microbial translocation in multiple sclerosis. Clinical Immunology, 183, 213-224. Fig 1, p. 220 The Synapse Adhesion Molecules Neurotransmitters Presynaptic Axon Terminal Postsynaptic Dendritic Spine Neurotransmitters Phenylalanine Amine Tyrosine s Dopa Catecholamine Indolamine s s Dopamine Serotonin Acetylcholine Dopamine Norepinephrine Melatonin Norepinephrine Epinephrine Epinephrine Neurotransmitters Amine Tryptophan s 5-hydroxytryptophan Catecholamine Indolamine s s Serotonin Dopamine Serotonin Acetylcholine Norepinephrine Melatonin N-acetylserotonin Epinephrine Melatonin Neurotransmitters Amine s Acetyl coenzyme A + Catecholamine Indolamine Choline s s Dopamine Serotonin Acetylcholine Acetylcholine Norepinephrine Melatonin Epinephrine Neurotransmitters Other Small Amino Peptide Gase Molecules Acids s s GABA Enkaphalins Nitric Oxide ATP Glutamate Substance P Carbon Adenosine Monoxide Glycine Insulin... others... others... others Oxytocin... others Empty Vesicles Neurotransmitters Neuropeptides are synthesized in the soma and are transported to the axon terminal via fast axoplasmic Neurotransmitter Reuptake: transport. Neurotransmitters enter empty vesicles in the axon terminal. Presynaptic Axon Terminal Active Zone Snare Protein Microtubule Translocation: Vesicles filled with neurotransmitters move into the active zone. Docking and Priming: Snare proteins attach to the vesicle and the axon membrane in preparation for neurotransmitter release. Axon Terminal Vesicle Pools Active Zones Rizzoli, S. O., & Betz, W. J. (2005). Synaptic vesicle pools. Rizzoli, S. O., & Betz, W. J. (2005). Synaptic vesicle pools. Nature Reviews Neuroscience, 6(1), 57-69. Figure 3b. Nature Reviews Neuroscience, 6(1), 57-69. Figure 3c. Vesicle Pools Reserve Pool (80-90%) Recycling Pool (5-20%) Readily Releasable Pool (
