Psych 261 Lecture 3 Jan 13 2025 PDF
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University of Waterloo
2025
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This document appears to be a lecture on neuroscience, specifically focusing on neurons, neurotransmitters, action potentials, and the blood-brain barrier. The lecture contains diagrams illustrating the various concepts discussed.
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A Common Scenario Communication occurs by chemicals called neurotransmitters. Axons conduct an electrical signal. Sir Charles Scott Sherrington...
A Common Scenario Communication occurs by chemicals called neurotransmitters. Axons conduct an electrical signal. Sir Charles Scott Sherrington Introduced the concept (1857-1952 CE): of the “synapse”. “So far as our present knowledge goes, we are led to think that the tip of a twig of the arborescence is not continuous with but merely in contact with the substance of the dendrite or cell-body on which it impinges. Such a special connection of one nerve cell with another might be called a ‘synapse’ [means ”joining together”]. The lack of continuity between the material of the arborization of one cell and that of the dendrite (or body) of the other offers the opportunity for some change in the nature of the nervous impulse as it passes from one cell to the other.” López-Muñoz, F., Boya, J., & Alamo, C. (2006). Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal. Brain Research Bulletin, 70(4–6), 391–405. Fig. 10, p. 403, quote from p.402. Efferent Axon: Carries a signal away from an area. Reference Area Afferent Axon: Carries a signal to an area. That’s my-elin Glia Astrocytes 30μ m Sloan, S. A., Darmanis, S., Huber, N., Khan, T. A., Birey, F., Caneda, C., Reimer, R., Quake, S. R., Barres, B. A., & Paşca, S. P. (2017). Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. Neuron, 95(4), 779-790.e6. Fig 1C, p. 780. The Blood-Brain Barrier Tight junction restricts passage of water-soluble molecules. Lipid-soluble agents (e.g., fats) and some gasses (CO 2) can passively move through membrane. Basal Lamina Pericyte Blood in Capillary Glucose Astrocyte Active transport of larger molecules (e.g., glucose, amino acids, insulin). Neuron Endothelial Cell Based on: Abbott, N. J., Rönnbäck, L., & Hansson, E. (2006). Astrocyte–endothelial interactions at the blood–brain barrier. Nature reviews neuroscience, 7(1), 41. Fig 2 & 3, p. 43 & 44. Astrocytes Forming a Blood-Brain Barrier BVL = Blood Vessel Heneka, M. T., Rodríguez, J. J., & Verkhratsky, A. (2010). Neuroglia in neurodegeneration. Brain research reviews, 63(1), 189-211. Figure 3. Astrocytes help form the blood-brain barrier. Astrocytes connect to other astrocytes for long-distance molecule transfer. Astrocytes serve as conduits for nutrients between the blood and neurons. Astrocytes create scaffolding that holds neurons in place. Blood in Capillary Astrocyte Neuron Astrocytes play a role in dilating and constricting blood vessels. The Tripartite Synapse Astrocyte Presynaptic Postsynaptic Axon Terminal Dendritic Spine Halassa, M. M., Fellin, T., & Haydon, P. G. (2007). The tripartite synapse: roles for gliotransmission in health and disease. Trends in molecular medicine, 13(2), 54-63. Figure 1, p. 55. Synchronization of Multiple Synapses Astrocyte Neuron Astrocyte envelopes multiple synapses (i.e., forming multiple tripartite synapses) and synchronizes activity at the synapses. Schwann Cells Schwann cells forming a Neuron segment of myelin. Axon Node of Ranvier Node of Ranvier Schwann cells each forming one segment Axon Jessen, K. R., & Mirsky, R. (1999). Schwann cells and their of myelin. precursors emerge as major regulators of nerve development. Trends in neurosciences, 22(9), 402-410. Figure 5. Oligodendrocytes Myelin Sheath Node of Ranvier Oligodendrocyte Neuron Neuron Axon Polydendrocytes (NG2 Cells) NG2 cells form precursors for oligodendrocytes. Thus, they are also called oligodendrocyte progenitor cells (OPCs). Polydendrocyte Oligodendrocyte Neuron NG2 cells can form synapses with neurons. NG2 cells help re-myelinate axons after injury. Polydendrocytes “may be important for integration in the brain because their processes pass through several neuronal layers and traverse grey and white matter.” Heneka et. al. (2010, p.193). Microglia Cortex Corpus Callosum Hippocampus From: Kettenmann, H., Kirchhoff, F., & Verkhratsky, A. (2013). Microglia: new roles for the synaptic stripper. Neuron, 77(1), 10-18. Figure 1. Development and Developmental Removal of synapse. removal of neuronal precursors. Synapse Removal of live glioma cells. Neuronal Precursor Glioma Cell Microglia Neutrophil Neuron Removal of neutrophil. Removal of stressed-but-viable neurons. Modified from Brown, G. C., & Neher, J. J. (2014). Microglial phagocytosis of live neurons. Nature Reviews Neuroscience, 15(4), 209-216.Figure 2. Microglia and Synaptic Pruning Synapse Dendritic Spine Axon Axon Axon Microglia Dendrite Kettenmann, H., Kirchhoff, F., & Verkhratsky, A. (2013). Microglia: new roles for the synaptic stripper. Neuron, 77(1), 10-18. Figure 3. Microglia and the Synapse Kettenmann, H., Kirchhoff, F., & Verkhratsky, A. (2013). Microglia: new roles for the synaptic stripper. Neuron, 77(1), 10-18. Figure 2. Radial Glia Surface of Cortex Migrating Neuron Radial Glia Malatesta, P., Hartfuss, E., & Gotz, M. (2000). Isolation of radial glial cells by Ventricle fluorescent-activated cell sorting reveals a neuronal lineage. Development, 127(24), 5253-5263. Figure 1B. The Action Potential The Early Greeks Psychic Pneuma e.g., Herophilus (325-255 BCE) Galen (130-200 CE) - Psychic pneuma is invisible like air - It is responsible for perception, cognition, and action - It emanates from ventricles and fills the nerves Luigi Galvani (1737-1798 CE) – Italian physiologist – Stimulated frog’s leg with static electricity – Nerves conduct electrical signal Johannes Muller (1801-1858 CE) – German physiologist – Law of specific nerve energies http://www.baillement. com/lettres/mueller_bio. html – Vitalism World Body Mind pressure Eye Brain Optic Nerve Experience Light of Light electricity Experience Sound of Sound Ear Auditory Nerve Adopted from Rachlin (2005) Hermann Helmholtz (1821-1894 CE) – German physiologist – Ophthalmoscope – Theory of colour vision – Theory of audition – Speed of nerve conduction http://en.wikipedia.org/wiki/ Hermann_von_Helmholtz#/media/File: Hermann_von_Helmholtz.jpg The action potential is an electrical signal that starts at The action potential the axon hillock. continues unattenuated down all branches of the axon. Axon Hillock Presynaptic Terminal The action potential travels down the axon and remains the same size as it travels down the axon. Hodgkin & Huxley Model Alan Hodgkin Andrew Huxley https://en.wikipedia.org/wiki/Alan_Hodgkin#/ https://en.wikipedia.org/wiki/ media/File:Alan_Lloyd_Hodgkin_nobel.jpg Andrew_Huxley#/media/File: Andrew_Fielding_Huxley_nobel.jpg Giant Axon of a Squid Tissue Surrounding Axon Squid Giant Axon Microelectrode Microelectrode placed inside a squid’s giant axon. (Each marking on the ruler measures 33 micrometers) Hodgkin, A. L., & Huxley, A. F. (1945). Resting and action potentials in single nerve fibres. The Journal of physiology, 104(2), 176-195. Plates 1 & 2, p.182 Intracellular Region Extracellular (-) Region (+) +40 Resting Potential: The inside of the cell is more negative than Voltage (mV) 0 the outside of the cell. Voltmeter -7 0 Tim e Stimulating a Neuron +40 Voltage (mV) 0 Threshold of Excitation: Depolarization beyond this point Depolarization: Decreasing the triggers an action potential. -6 potential across the membrane. 5 -7 Resting Potential: The potential when the neuron is at rest. 0 Hyperpolarization: Increasing the potential across the 0 1 2 3 membrane. Time (ms) Stimulation The Action Potential +40 Overshoo t Downstr Voltage (mV) e 0 Spike height Upstrok ok e Threshold of Excitation: Depolarization beyond this point triggers an action potential. -7 Afterhyperpolarizatio 0 n 0 1 2 3 (or Time hyperpolarization) (ms) Based on: Bean, B. P. (2007). The action potential in mammalian central neurons. Nature Reviews Neuroscience, 8(6), 451-465, Box 1. Hodgkin & Huxley (1945) Voltage (mV) Time (ms) An example of an action potential measured by Hodgkin & Huxley Hodgkin, A. L., & Huxley, A. F. (1945). Resting and action potentials in single nerve fibres. The Journal of physiology, 104(2), 176-195. Plates 1 & 2, p.182 Ion Concentrations Intracellular Region Extracellular Region (-) (+) Voltage- Sodium Dependent (Na+) Ions Sodium Channel Potassium Voltage- (K+) Ions Dependent Potassium Channel Voltage- Chloride (Cl-) Ions Dependent Chloride Channel Negatively (- Sodium-Potassium Charged Proteins (Protein-) ) Pump The Potassium Channel Extracellular Fluid Cell Membrane Intracellular Fluid Close Open d Kuo, A., Gulbis, J. M., Antcliff, J. F., Rahman, T., Lowe, E. D., Zimmer, J.,... & Doyle, D. A. (2003). Crystal structure of the potassium channel KirBac1. 1 in the closed state. Science, 300(5627), 1922-1926. Figure 6, The Sodium-Potassium Pump 3 Na+ Extracellular Region Cell Membrane Intracellular Region 2 K+ Movement of Ions Diffusion: Molecules tend to move from areas of high concentration to areas of low concentration (i.e., across a concentration gradient). Concentration Low Concentration High Concentration Gradient Movement of Ions Electrostatic Force: Particles with the same charge repel each other and particles with opposite charges attract each other. Intracellular Region Extracellular Region (-) (+) (- Electrica ) l Force (- Sodium ) (Na+) Ions Diffusio n Potassium (K+) Ions Diffusio Electrica n l Force Electrica Diffusio Chloride l n (Cl-) Ions Force (- ) Intracellular Region Extracellular Region (- ) Sodium (Na+) Ions +40 Voltage (mV) Potassium (K+) Ions 0 -7 0 Tim (- e ) Intracellular Region Extracellular Region (- ) +40 Voltage (mV) 0 -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e ) closed. Intracellular Region Extracellular Region (- ) Na+ channels open rapidly. K+ channels open very slowly. +40 Voltage (mV) 0 Depolarizing stimulation brings cell to threshold. -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e ) closed. Intracellular Region Extracellular Region Na+ channels remain open. K+ channels reach maximal (- opening. ) Na+ channels open rapidly. K+ channels open very slowly. +40 Voltage (mV) 0 Depolarizing stimulation brings cell to threshold. -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e ) closed. Intracellular Region Extracellular Region Na+ channels remain open. K+ channels reach maximal (- opening. ) Na+ channels open rapidly. K+ channels open very slowly. Na+ channels close. K+ channels remain open. +40 Voltage (mV) 0 Depolarizing stimulation brings cell to threshold. -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e ) closed. Intracellular Region Extracellular Region Na+ channels remain open. K+ channels reach maximal (- opening. ) Na+ channels open rapidly. K+ channels open very slowly. Na+ channels close. K+ channels remain open. +40 Voltage (mV) 0 K+ channels close. Depolarizing stimulation brings cell to threshold. -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e ) closed. Intracellular Region Extracellular Region Na+ channels remain open. K+ channels reach maximal (- opening. ) Na+ channels open rapidly. K+ channels open very slowly. Na+ channels close. K+ channels remain open. +40 Voltage (mV) 0 K+ channels close. Depolarizing stimulation brings cell to threshold. -7 0 Tim (- Resting Potential: K+ channels are partly open; Other channels are e Sodium-potassium pump moves 3 Na+ out for 2 K+ closed. in. ) Absolute Refractory Relative Refractory Period Period +4 0 Voltage (mV) 0 -7 0 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. +40 +40 Voltage (mV) Voltage (mV) 0 0 -7 -7 0 0 Tim Tim e e Weak Stimulus Strong Stimulus