HMB200H1 Final: L3 How is the Brain Wired? How do Neurons Communicate?

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University of Toronto St. George
Human Biology
Franco Taverna

Lecture 3 How is the Brain Wired? How do Neurons Communicate? Kolb & Whishaw 5E: §4.1-4.2 (to Graded Potentials), 4.4, 11.4 (Spinal Reflexes only) “Brain City Analogy”, “Reflex Arc”, and “Electrical Signaling” Videos How does the brain communicate? Cranial nerve mnemonic: Ollie opted out of Trojan’s triggering abduction fair to avoid grappling with various sporting accessories. Hooray! • One of our teachers taught a French girl valuable skills. Haha. • Once one orangutan took three albinos fishing and guzzled vodka and Hennessey Sensory (S), motor (M), both (B): • Some say marry money but my brother says big brains matter most Cranial Nerves Cranial Name Function Nerve I Olfaction Smell II Optic Vision III Oculomotor Eye movement IV Trochlear Eye movement V Trigeminal Masticatory movements and facial sensation VI Abducens Eye movement VII Facial Facial movement and sensation VIII Auditory Vestibular Hearing and balance IX Glossopharyngeal Tongue and pharynx movement and sensation X Vagus Heart, blood vessels, viscera, movement of larynx and pharynx XI Spinal Accessory Neck movement XII Hypoglossal Tongue movement Looking for leaders for HMB200 Geneva Centre for Autism fundraiser! Email: [email protected] • Tuesday, January 24 Lecture Outline: I. Written Debate Assignment II. The Brain Like a City – Analogy to Reflexes III. Diffusion and Concentration Gradients IV. Electrical Gradients V. Membrane Potentials – Electrochemical Gradients VI. Preview for Action Potentials Debate Assignment The debate assignments build toward a final assignment that is • First part of the debate assignment involves submitting a draft that builds towards the whole assignment modeled after a “debate”, formulating two sides to an issue, and a persuasive argument, finding and using evidence for and • Draft = debate question and short annotated bibliography • Final version involves expansion and evaluation for conclusion against the sides to form a conclusion. • Evidence Neuroscience myth: You only use 10% of your brain. o One original research article for/against each side • Evaluate and form conclusion (pick one side!) • Hypothesis: you only use 10% of your brain • Find evidence to confirm or refute it o Based solely on that evidence o Must use Pubmed/Medline to find original • Want to refute null hypothesis, but now we need to have two sides of research articles (not review articles) this • What piece of evidence suggests that we only use 10% of the brain? The brain has limited amounts of energy such that only 10% of neurons are firing at a point in time. Debate Assignment: Brainstorm a Question Think of your favourite neuroscience “myth”. • Alternative could be that we’re using 10% of our brain at a given time, relatively speaking, but all the time, we’re using 90% of our brain Debate Assignment: Effective Scientific Questions o We’re always using 100% of our brain, but 10% varies Create a question based on that myth. depending on the task • For this assignment, it must NOT be a simple yes or no • Single best characteristic of a good hypothesis: testable question or hypothesis • Unless there’s some way to test it, it’s just a crazy idea – might as well be illogical • Rather, you must have two distinct sides Question with two alternative sides, based on the 10% myth: What is the single best characteristic of a good hypothesis? The Brain-City Analogy: An Analogy to Simple Reflexes • Brain is an analogy for a city, Dr. Ju is the sensory receptor (smoke alarm) • Structure with respect to connectivity drives the function of the brain • Just like simple reflex arcs, it depends on specific motor neurons – but there are more parallel and hierarchical structures in the brain • Something happens in the periphery, you feel it, along with simultaneous spinal reflex, the signals are sent up the brain • There are also direct connections to the output – amygdala (dispatcher), sending signals out to the hypothalamus • Complexity comes from the vast connectivity – direct and indirect, through associative areas and lead to output 2 “Perceptual World” Created from Sensory Receptors… Translated into the “Language” of the CNS • Every sensory organ and system has it’s own uniquely tuned dendritic end of neurons, able to sense that particular stimulus • From light to sound to olfactory cues, to taste cues, and to touch (stretch, heat, cold, etc.) For different kinds of sensations, different kinds of receptor cells. Rod and cone cells of the eye’s retina are specialized to respond to the electromagnetic radiation of light. The ear’s receptor neurons are topped by hair bundles that move in response to the vibrations of sound. Olfactory neurons at the back of the nose respond to odourant chemicals that bind to them. Taste receptor cells on the tongue and back of the mouth respond to chemical substances that bind to them. Meissner’s corpuscles are specialized for rapid response to touch, while free nerve endings bring sensations of pain. Sensory Signals Activate Sensory Receptors • Somatosensory system • Touch on the skin activates some receptors when skin stretches (hair displacement, skin movement, temperature, etc.) • Most of the receptors function this way • Within those neurons, specialized for specific somatosensory inputs, there are proteins called ion channels • Ion channels are activated by very specific means – stretch, for example, and open in some way via structural changes 3 Ion Channels: Properties and Examples When channels open, they become permeable to ions. Properties: each channel has unique: • Structure • Ion selectivity • Dynamics • Means of activation E.g., sensory, ligand, voltage, etc. • Analogous in structure, with transmembrane domains • Key structure function concept is that with some small movements, a literal aqueous hole opens up in the middle of these proteins • Shifting/conformational change is sensitive and caused by the activation via stimulus (e.g., stretch of skin) • There are >1000 different ion channels, each with a slightly different structure, ion selectivity, dynamics (how it opens and closes and at what rate/duration), and what activates it • Hence the massive complexity of the brain • There are simple rules, but lots of options for those rules  complexity emerges from this • Because of the variety of stimuli and the various channels, great complexity and seemingly intelligence emerges Ion Flow Can Cause Voltage Changes • Depending on which ions flow, we can get different charges across the membrane • Hyperpolarization if K flows out of the cell or if Cl flows into the cell 4 Signaling in Neurons e.g., sensory input opens cannels for certain ions • Some stimulus activates Na channels, allowing Na ions to + enter • E.g., Na allowed to enter  changes the charge distribution (voltage) locally • In and around the channel, there is a large influx of positive • Charge change passively diffuses away charges, changing the charge distribution inside and outside the cell • Can be hyperpolarization or depolarization • This charge simply diffuses down the dendrite towards the • This is what happens at synapses and sensory receptor endings soma, via passive diffusion of these ions • This is called a graded signal, meaning that - relative to the size of the positive charge is directly related to the size of number of charges that go in in the first place • Allows translation of intensity of the signal • It can be hyperpolarized or depolarized, depending on the type of channel and ion that is involved Neural Signaling is not like Electricity • Flow of information in the nervous system is too slow to be a flow of electricity (von th Helmholtz, 19 century) o Nerve conduction: 30-40m/s o Electron flow: 3x10 m/s • It’s not the charge (not like the flow of electrons), but the wave of charge (diffusion of ions) that travels along an axon (Bernstein, 1886) • Electricity is the movement of electrons through a conductor • The movement of electrons is what carries the energy • This is not the case in neurons – part of the flow of electricity is simply the diffusion of these ions • These atoms diffuse out like a wave • It’s the change in charge distribution caused by the movement of ions that carries the signal, not the flow of electrons itself What Happens in Neurons? The Nobel Prize in Physiology and Medicine, 1963 • J. Young in the 1930s actually discovered the giant axons in the squid “…for their discoveries concerning the ionic mechanisms involved in excitation and inhibition in the peripheral and central portions of the nerve cell membrane.” 5 Measurement of Ion Concentrations • These familiar values came from those initial experiments Concentrations of ions inside and outside freshly • These are typical values of concentrations inside and outside neurons isolated axons of squid • These numbers vary a little from species to species, but relative Concentration (mM) concentrations remain the same • Calcium typically has activating protein properties, rather than electrical properties Ion Axoplasm Blood Seawater Potassium 400 20 10 Sodium 50 440 460 Chloride 60 560 540 a Calcium 0.m µM 10 10 a Ionized intracellular calcium from Baker, Hodgkin, and Ridgeway, 1971 Active Transport of Ions Can Move Them Against Concentration Gradients • Concentration gradients are created and maintained (with great energy expenditure) by pumps o E.g., ATPase ion transport proteins • Concentration gradients will result in diffusion, if those molecules are allowed to flow • Generated and maintained in neurons by the action of ATPases • Use energy of ATP to transport ions against their concentration gradients (3 Na out, 2 K in) • Some ATPases transport calcium, hydrogen, etc. and use a lot of the energy that the brain uses Ion Concentration Differences Result in Voltage Differences (Maintained by Pumps) The differences in ion concentrations, plus the large concentrations of negatively charged proteins (DNA, RNA, etc.) in the cell  electrical gradients • Difference in concentration of these ions plus the negatively charged proteins (DNA and RNA) inside the cell results in observation of 60-70mV difference in charge, with inside of the cell being more negative • Arbitrarily assign 0mV to outside Work area cont’d… Outside the Cell • Equilibrium of K voltage and concentration gradients results in some K remaining outside the cell  K contribute to the charge across the membrane + - • Na and Cl also take part in producing the resting potential • Gated Na channels are usually closed, blocking entry of Na • Given enough time, sufficient Na leak into the cell to neutralize its membrane potential; cell membrane has mechanism to prevent this neutralization + + + • When Na leaks into the neuron, they’re immediately escorted out again via the Na /K -pump • K is free to leave the cell through open K channels, but closed Na channels slow the reentry of Na o In this way, Na is kept out (10 times as much outside), creating a difference in Na concentrations that contributes to the membrane’s resting potential • Cl moves in and out of the cell through open channels in the membrane o Equilibrium point is approximately the same as the membrane’s resting potential, so Cl ordinarily contribute little to the resting potential o There are about 12 times as many Cl outside the cell as inside it The cell membrane’s semipermeability and actions of its channels, gates, and pumps produce voltage across the cell membrane: its resting potential. 6 Diffusion Principles 1. If a Y channel opens, what does it look like at equilibrium? a. b. X and Y are not charged. c. Unknown, but there will be 100mM X and Y on each side (some random distribution of both) Is there movement of molecules at equilibrium? Because these molecules are at such low concentrations relative to the solvent, they are essentially acting independent of each other. There is always movement of molecules, the net movement is zero. Diffusion Diffusion: movement of a substance from an area of higher • Because solvent > solute, diffusion seems to act independently for each substance concentration to an area of lower concentration through random • Diffusion is not considered a force itself motion (e.g., bumping into solvent molecules) • But concentration gradients do create a pressure and movement of • Seems to act independently for each substance (i.e., X those molecules, acting like a force almost doesn’t seem to bump into Y) • Because solvent molecules greatly outnumber solute molecules What Makes Molecules Move? • If those species are charged, then an electrical gradient can 1. Concentration Gradients (promotes diffusion) cause them to move, repelling like charges or attracting • Differences in concentration of a substance among regions opposite charges of a container causes diffusion from an area of higher • These electrical charges act equally on all species concentration to an area of lower concentration • What moves these molecules? • Concentration gradients/diffusion seem to act independently for each substance 2. Electrical Gradient/Voltage (driving force for ions) • Difference in charge between two regions that allows a flow of current if the two regions are connected • Ions will move down a charge gradient from an area of higher charge to an area of lower charge • Opposite c
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