Action Potential Conduction Down the Axon - PDF

ACTION POTENTIAL CONDUCTION DOWN THE AXON  every step isactive ACTIVE PROPAGATION – UNMYELINATED AXON...

ACTION POTENTIAL CONDUCTION DOWN THE AXON  every step isactive ACTIVE PROPAGATION – UNMYELINATED AXON if not attached to cell body & only happens when ? information travel short how do you get stimul bump distences ; usually in some region from of the previous segment &xon's depolarization of the broin unmyelinated neuron floats over through ICE get flipping of membrane OpenSNot works its way down the a xo n of - membrane piece of member sodium from previous leas through and allow action potential to travel down to piece Segment axon termind is active propagation P action potential Only travel in o n e direction. refractory period prevents action potential from traveling in the wrong direction toward the cell body ▪ Active propagation of action potential is slow (10 m/s), but does not weaken ▪ Takes many small steps down the axon – some chance of failure at every step a very unlikely to fail  PASSIVE PROPAGATION – MYELINATED AXON & beyond the neighboring nerrons ▪ Action potential triggered at axon hillock, moves passively through the myelinated segment – quick (150 m/s), but ion channels isbed signa weakens as it signal weakens as it travels greater chance of failure absence of myelin & ▪ At Node of Ranvier, it regains ~ where ion channels and Nat/Kt pump located d moves passively full charge through active means (Na/K channels) ↑ has to mere the Apcon be generated flow all the way to the ▪ Then moves passively through main difference Avs4 = Not has to travel further Next Node if not... of Renvier Ap is lost next myelinated segment  CLASS QUESTION If someone is exposed to a toxin that blocks voltage- gated Na+ channels, their action potentials will______ A. Get smaller B. Not be generated C. Get larger Answer: B?  TOXINS TARGET VOLTAGE-GATED CHANNELS ▪ Tetrodotoxin (puffer fish) and saxitoxin (algae) block voltage-gated Na+ channels ▪ Batrachotoxin (frog) forces Na+ channels to stay open ▪ Agitoxin (scorpion) and beta- bungarotoxin (snake) block voltage- gated K+ channels HOW ARE ACTION POTENTIALS CONVERTED INTO CHEMICAL SIGNALS AT THE SYNAPSE? PRE-SYNAPTIC SIDE  AN ACTION POTENTIAL CAUSES NEUROTRANSMITTER RELEASE ▪ Action potential reaches the pre- synaptic axon terminal: action opens potential chennels → voltage-gated Ca+2 channels open → Ca+2 enters terminal * the important trigger for the release of neurotrons mitter → Ca+2 causes synaptic vesicles to fuse with the presynaptic membrane → release neurotransmitter into the synaptic cleft = exocytosis  STEPS OF EXOCYTOSIS ▪ Vesicles are packets of neurotransmitters ▪ SNARE proteins: on the membrane → v-SNARES and t-SNARES vesicular - oxon termine tronomembrane shores → docked at presynaptic membrane, Shores waiting to fuse before Ap recenes terminal the vesicle pull towards exon membrane No trigger for binding of snores reside is transported close to axon terminal and close proximity allows shore to interest close - but hothing  STEPS OF EXOCYTOSIS ▪ Voltage-gated Ca+2 channels open ↳ by the action potential ▪ Ca+2 sensor: synoptorgmin -a binds → Synaptotagmin pulls physically vesicle closer to exon terminal - fuse colcium → Fusion and neurotransmitter release  CLASS QUESTION If someone is exposed to a toxin that changes neurotransmitter release at muscles, they may experience ______ O A. Muscle weakness or paralysis contracting O B. Muscle tightening or spasms reloxing O C. Death ? ofalltheofabove Answer: All the above  ALL ABOUT NEUROTRANSMITTERS!  NEUROTRANSMITTERS ▪ Basis of communication between neurons ▪ Many different chemicals act as neurotransmitters in brain: motor neurons make ACn → Glutamate, GABA, dopamine, serotonin, norepinephrine, - acetylcholine Specific combination based on the type of neuron ▪ Each neuron uses one (or maybe two or three!) neurotransmitters; different neurons use different neurotransmitters ▪ Each neurotransmitter can trigger a different effect on the post-synaptic cell from (often away enzyme not · converte on amino did we derive our dief into a neurotransmitter ,  NEUROTRANSMITTER PRODUCTION ▪ Neurons must synthesize their neurotransmitter and move it into vesicles ▪ A specific enzyme (protein) is involved in producing each neurotransmitter ▪ Often, that enzyme converts an amino acid we derive from our diet into a neurotransmitter SYNAPTIC CLEFT  NEUROTRANSMITTERS CROSS THE SYNAPTIC CLEFT Waves of release a re discrete waves ▪ Neurotransmitters diffuse across until they reach the post- synaptic membrane ▪ Extra neurotransmitter is * recycling degraded by enzymes, or taken up by presynaptic terminals or astrocytes (tripartite synapse) a lot of neurotronsmitted I exce degraded or are released then needed in taker book to hopes they repen the other side pre-synoptic or taken by astrocytes to book to go pre- POST-SYNAPTIC SIDE  POST-SYNAPTIC DENSITY ▪ Dendrites/spines have post-synaptic densities with receptors proteins neuro will bind ▪ Neurotransmitters bind to receptors on post-synaptic membrane  RECEPTORS ▪ Ionotropic receptors fast → Ligand-gated ion ↑ channels needs neuro bound to be activated opens on ▪ Metabotropic receptors Not ion channel Dostsynaptic and ions flow in out → Receptor activates Slow G-protein G PCR receptors - when bound activate by neuro introcellular can eventually , much lead to you more slowly → G-protein activates ion Diochemical pathway ion Channel open channels and other biochemical processes  IONOTROPIC RECEPTORS ▪ Chemically activated by neurotransmitter binding Several diff cations - ▪ Cation (Na+, K+, Ca+2) or = anion (Cl-) channels - just chloride Heteropentamer ▪ Fast response  METABOTROPIC RECEPTORS ▪ Chemically activated by neurotransmitter binding ▪ Coupled to G-proteins, which in G protein Signal/travel turn couple to other enzymes/channels (GPCR) within cell Dind to ion Channel to open 7 transmembrane proteins ▪ Slower biochemical changes Extracellular within the cell (second messenger systems) Intracellular  AGONISTS AND ANTAGONISTS &minis s neurotransmitter # bound by neuro agonist Only stoye open when agonist binds * prevents the neurotrans from binding doesn't close the receptor but prevents it from opening antagonist can compete of the agonist Unbound An naturally occurring molecule (ligand) or drug Some substances bind receptor. can bind to the receptor and open in. Called an to receptors but do Receptors are agonist. not activate them. normally closed. Instead, they simply post synoptic true for both block agonists from side will not be able to hore receptor binding to the Neuro from binding receptors. These are artogonists prevent classified as first neuron a second neuron from antagonists. communicating ↳ eX : Norcan Kicks off opioid Lagonist) to prevent Opioid from binding  CLASS QUESTION Ligand-gated ion channels are activated by ____ A. Ions ⑧ B. Neurotransmitters C. Voltage D. Temperature Answer: B?  HOW ARE NEUROTRANSMITTER SIGNALS CONVERTED TO ELECTRICAL SIGNALS IN DENDRITES/SPINES?  NEUROTRANSMITTERS/RECEPTORS OPEN POST-SYNAPTIC ION CHANNELS ▪ Cation (Na+, K+, Ca+2) or anion (Cl-) channels ▪ Electrically-charged ions cross membrane = post-synaptic potential (PSP) ▪ Excitatory or Inhibitory PSP + 7 (t into neuron into ion Channels ▪ PSP can spread through dendrite to cell body and axon hillock travel along membrane to cell body  NEURONS ARE FUNCTIONALLY COUPLED action potential * there's a coupling after action comes potential (t) only a few my in size specifiers)→ Excitatory Post-Synaptic Potential (EPSP) come→ Inhibitory Post-Synaptic Potential (IPSP) neg  ELECTROCHEMICAL TRANSMISSION ▪ Chemical: → Pre-synaptic cell releases neurotransmitter onto post- synaptic cell ▪ Electro: → Excite or inhibit the post-synaptic cell → Alter the biochemical processes within the post-synaptic cell via G-proteins  FULL SUMMARY (1) The action potential is propagated over the presynaptic membrane (2) Depolarization of the presynaptic terminal leads to influx of Ca+2 Enzymes and precursors for (3) Ca+2 promotes exocytosis, the fusion synthesis of neurotransmitters of vesicles with the presynaptic membrane, and vesicle wall are continuously which releases transmitter into the cleft transported to axon terminals (4) The binding of neurotransmitter to receptor molecules in the post-synaptic membrane opens channels. This permits (7) Transmitter binds to ion flow and initiating an excitatory or autoreceptors in the inhibitory post-synaptic potential presynaptic membrane (5) Excitatory or Inhibitory post-synaptic potentials spread over dendrites and cell body to the axon hillock (6b) Reuptake of neurotransmitter slows synaptic action and recycles (6a) Enzyme present in the neurotransmitter for extracellular space breaks subsequent transmission down excess neurotransmitter  CLASS QUESTION Whether a PSP is excitatory or inhibitory depends on the ____ A. Type of neurotransmitter released B. Size and shape of the action potential C. Type of voltage-gated channel that opens does the post-synoptic have the right receptor Answer: A? & C HOW DO CELLS PROCESS EPSP AND IPSP INFORMATION?  EPSPS AND IPSPS ▪ Cations enter cell → membrane potential becomes less negative → Depolarizes (less polarized) → Excitatory post-synaptic potential ▪ Anions enter cell (or cations exit) → membrane potential becomes more negative → Hyperpolarizes (more polarized) → Inhibitory post-synaptic potential  SUMMATION AND INTEGRATION ▪ Dendrites receive contacts from many neurons ▪ Individual EPSP/IPSP is very small and graded ▪ Summation = combining signals Size + charge ▪ Integration = translating signals into a EPSP + 1 IPSP - 3 decision on whether to send an output will end up wh hyperpoler to the next neurons Use combination  SPATIAL SUMMATION : th ove r ▪ Spatial summation occurs if potentials come from different parts of the cell summation across different places on the post syneptic this is how the con & be result EPSP build up of to resen thethreshold spetid For summation triggering of action potential  TEMPORAL SUMMATION multiple AP coming down 1 EPSP ZEPP JEPT ▪ Temporal summation occurs if potentials arrive at axon hillock at slightly different times EPSP builds on each other in both of summation types have to reoch-55 to -40 & exon hillock oetrole to Ap  INTEGRATION has to sum up ot ▪ Many excitatory and inhibitory inputs are summed · - SS to -40 to IPSP activate ▪ If the sum reaches threshold potential, an action potential is triggered EPR → Action potentials begin at the axon hillock (initial segment of the axon) eX : during sleep we went IPSP > EPSP so we don't more uncontrolled excitability-seizures INTEGRATION  CLASS QUESTION True of False: Temporal summation is more important than spatial summation in action potential generation A. True B. False O Answer: B? both are equally important and can be the some happening in neuron / synopse  SUMMARY ▪ Pre-synaptic → SNAREs → Voltage-gated calcium channels → Exocytosis ▪ Post-synaptic receptors → Ligand-gated ion channels → Metabotropic receptors → Agonists & Antagonists → Excitatory post-synaptic potentials & Inhibitory post-synaptic potentials → Spatial and Temporal summation HOW CAN CHEMICALS AFFECT NEURON COMMUNICATION? Chapter 4 WHAT ARE NEUROTRANSMITTERS?  WHAT ARE NEUROTRANSMITTERS? ▪ Criteria for what is a neurotransmitter: → Synthesized and stored in presynaptic if S not mode + store it can't do its job neuron red& → Released from presynaptic axon terminal by an action potential action potential trigger must relede → Has specific receptors that recognize it on postsynaptic membrane  WHAT ARE NEUROTRANSMITTERS? either make (exclusive a re fra ▪ Types of neurotransmitters: or the other & → Amino acids or derivative of amino acids – glutamate, GABA, & dopamine, serotonin, norepinephrine, acetylcholine → Small proteins – neuropeptides → Steroids → Gases – nitric oxide, carbon monoxide → Lipids – endocannabinoids ▪ Cell can contain several neurotransmitters that can be co-released individual neuron Con make t release multiple neuro  MAIN TYPES OF NEUROTRANSMITTERS Classic = directly open ion channels come ; directly EPSP + 1991  GLUTAMATE AND GABA most abundent in CNS ▪ Glutamate and Gamma-Amino-Butyric Acid (GABA) are the most abundant neurotransmitters in the brain #glutomote is found in + broin spinel cord ▪ Glutamate is the main excitatory neurotransmitter EPSPs * GABA in broin → Excitation allows one neuron to activate another glycine * is GABA equivalent in spine cord Iglycine + glutomate a re also exclusive) BRAIN ▪d GABA is the main inhibitory neurotransmitter IPSPs glyake Spine → Inhibition stops/blocks the activation of a neuron in ▪ Seizures and loss of consciousness/coma can result from glutamate/GABA imbalances  GLUTAMATE ▪ Glutamate is released by terminals and acts on a number of receptors a → 3 ionotropic receptors: AMPA, NMDA and Kainate receptors → 1 class of metabotropic receptors: mGluR GLUTAMATE RECEPTORS ▪ Ionotropic: AMPA receptor and Kainate receptor → Cation: Na+ enters cell, K+ leaves cell → Overall main effect is Na+ enters cell → EPSP Net primarily convey outside concentration gredient When open Not enter -> more codium Not bring in I +leave because A lot enter more then Net K+ ↳ more "inside so wants to leave leaving But also theres (1 & in cell Still will be excititory  GLUTAMATE RECEPTORS need depolarization of the membrane & IEPSP binds I will kick out &hen e Mg2 + and ions will be oble in to Flow go ? generates AMPA or Keinate ReCeDTOD -- needs to ▪ Ionotropic: NMDA receptor is both ligand-gated and voltage-gated → Glutamate be bound by glutamate → Mg2+ block released by depolarization and membrane needs to be to depolorized open → Cation: Na+ & Ca2+ enter the cell, K+ leaves cell creates 2nd bigger EPSP → Overall effect isNa+ & Ca2+ enter cell → EPSP  GLUTAMATE RECEPTORS generally found neer each other for this to happen 1 - ▪ Activation of AMPA receptors can release Mg2+ block and open NMDA receptors - creates EPSI con depolor provide to Open NMDA ↓ generates EPJP more GLUTAMATE RECEPTORS ▪ Activation of AMPA receptors can release Mg2+ block and open NMDA receptors ▪ Important in learning and memory #  GABA main neuro for inhibition in broin neuron will post synoptic have inhibitory effect ▪ GABA is released by terminals and acts on a number of receptors → 2 ionotropic receptors: GABAA and GABAC → 1 class of metabotropic receptors: GABAB  released from con be ↑ presynaptic GABA RECEPTORS - present in spine GABA bind b GABAA to open receptor GABAA is main ligand ▪ Ionotropic: GABAA receptor ~ other do not open : → Cl- enters cell inhibitory - effect → IPSP → Binding sites for drugs that increased receptor function e.g. sedatives, anesthetics, alcohol receptor causes the dexi propofol to stoy open for longer if GABA ion Channels Stay open too long : only GABA can open * too much Cl-enter the cell lot of inhibition of the corsing a increase but drugs the cell-loss of consciousness time of opening respiratory distress GLYCINE/GLYCINE RECEPTORS onis g samemechon ▪ Ionotropic: Glycine receptor → Cl- enters cell inhibitory a → IPSP → Spinal cord, brainstem ↳ main inhibitory in spind Cord  more exam like question CLASS QUESTION A seizure can be caused by too much _______, and a coma can be caused by too much _______ A. GABA, glutamate ⑧ B. glutamate, GABA C. GABA, glycine Answer: B?  NEUROMODULATORY TRANSMITTERS role = make information in CNS = primanly meta less do not directly) quickly more or important couse transfer of info Will strengthen/dampen I released know where being mode information from classic neurotron s mitters + impoct NOREPINEPHRINE/NORADRENALINE (NE) ▪ Originates in locus coeruleus and * mode only projects throughout brain in this but is region sent → Arousal and sleep/wake throughou broin/body everywhere the → Mood /Stress/anxiety (negative emotions) → Cognitive function ↳ gets optimized for decision making in stress response situations ▪ Sympathetic ↳ nervous system mein neuro in Fight/flight only meta ▪ Metabotropic α1, α2, β1 and β2 receptors ▪ Anxiety, stress, hyperarousal, ↳PTSD treatment includes that inhibit drugs NE SEROTONIN (5-HT) Specific production location ▪ Originates in dorsal raphe and projects throughout brain every broin region → Sleep/wake cycle → Feeding (hunger and satiety) → Mood most are meta ▪ Metabotropic 5-HT receptors (15 receptors) ▪ Anxiety, depression (Prozac) , Schizophrenia 2X : SSRIs es treatment too much NE too little SHT in anxiety in anxiety DOPAMINE (DA) different role based on where released ▪ 1) Originates in ventral tegmental M & area and projects to limbic and cortical areas two overlapping → Reward and reinforcement broin regions but participate 2 throughout whole cortex in very diff circuits involved in addiction ▪ 2) Originates in substantia nigra and projects to striatum/caudate → Motor control eX : Parkinson's a deeth of dopomine in sub nigre ▪ Metabotropic D1-D5 receptors ▪ Schizophrenia, drug addiction, Parkinson’s disease  CNS PNS ACETYLCHOLINE (ACh) + Y two diff roles ▪ In CNS → Originates from the basal forebrain → Cholinergic cell bodies and * make Ach projections contain acetylcholine released widely → Ionotropic: Nicotinic acetylcholine ↳ receptor nicotine also binds Our broins don't make nicotine but ACh → Metabotropic: Muscarinic acetylcholine receptor → Lost in Alzheimer’s disease  ACETYLCHOLINE (ACh) ▪ In PNS → Are Neuromuscular junction um post → Ionotropic: Nicotinic acetylcholine receptor in our muscles Ach receptor in PNS ? Why don't h ove we metabotropic ↑ speed need muscles to contract quickly ex : if someone has Ms you won't get Ach releest deteristes be myelin o n oxon s muscle post synaptic · ignol not bright to Not really side doesn't & neuromuscular a synopse move dendrites etc unation. J loo , precynepliz it of the usual is port muscle muscle does not here dendrites or spires but has iotrophic Channel  CLASS QUESTION Neuromodulatory transmitter receptors tend to be ______ ↳ mostly A. Ionotropic O B. Metabotropic Answer: B?  SUMMARY Seizure : too much glutamate ▪ Post-synaptic receptors too little GABA → EPSPs & IPSPs → Integration ▪ Main types of neurotransmitters → Glutamate, GABA, Glycine ▪ Neuromodulatory transmitters → Norepinephrine, Serotonin, Dopamine, Acetylcholine ▪ Drugs → Agonists/antagonists, Drug tolerance