Chapter 4 Neural Conduction and Synaptic Transmission How

The Neuron’s Resting Membrane Potential l l Inside of the neuron is negative with

Ionic Basis of the Resting Potential l l Ions, charged particles, are unevenly distributed

Ionic Basis of the Resting Potential l Homogenizing • • l Random motion –

Ions Contributing to Resting Potential l l Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively

The Neuron at Rest l l Ions move in and out through ion-specific channels

Equilibrium Potential l l The potential at which there is no net movement of

The Neuron at Rest l l Na+ is driven in by both electrostatic forces

Something to think about l l What would happen if the membrane’s permeability to

Generation and Conduction of Postsynaptic Potentials (PSPs) l l Neurotransmitters bind at postsynaptic receptors

Generation and Conduction of Postsynaptic Potentials (PSPs) l l Postsynaptic depolarizations = Excitatory PSPs

EPSPs and IPSPs l l l Travel passively from their site of origination Decremental

Integration of PSPs and Generation of Action Potentials (APs) l l In order to

Integration l l l Adding or combining a number of individual signals into one

What type of summation occurs when: l l One neuron fires rapidly? Multiple neurons

The Action Potential l l All-or-none, when threshold is reached the neuron “fires” and

The Ionic Basis of Action Potentials l l l When summation at the axon

The Ionic Basis of Action Potentials l l l Rising phase: Na+ moves membrane

$Refractory Periods l l l Absolute – impossible to initiate another action potential Relative$

The action potential in action l l http: //intro. bio. umb. edu/111112/112 s 99

PSPs Vs Action Potentials (APs) l l EPSPs/IPSPs Decremental Fast Passive (energy is not

Conduction in Myelinated Axons l l Passive movement of AP within myelinated portions occurs

Structure of Synapses l Most common l Dendrodendritic – capable of transmission in either

Synthesis, Packaging, and Transport of Neurotransmitter (NT) l NT molecules • Small • Synthesized

Release of NT Molecules l l Exocytosis – the process of NT release The

Activation of Receptors by NT l l Released NT produces signals in postsynaptic neurons

Receptors l l l There are multiple receptor types for a given NT. Ionotropic

Ionotropic Receptors l l l NT binds and an associated ion channel opens or

Metabotropic Receptors l l Effects are slower, longer-lasting, more diffuse, and more varied. NT

Reuptake, Enzymatic Degradation, and Recycling l l l As long as NT is in

Small-molecule Neurotransmitters l l Amino acids – the building blocks of proteins Monoamines –

Amino Acid Neurotransmitters l l Usually found at fast-acting directed synapses in the CNS

Monoamines l l l Effects tend to be diffuse Catecholamines – synthesized from tyrosine

Soluble-Gases and ACh l l Soluble gases – exist only briefly • • Nitric

Neuropeptides l l Large molecules Example – endorphins • “Endogenous opiates” • Produce analgesia

Pharmacology of Synaptic Transmission l Many drugs act to alter neurotransmitter activity • Agonists

Agonists – 2 examples l Cocaine - catecholamine agonist • Blocks reuptake – preventing

Antagonists – 2 examples l l Atropine – ACh antagonist • Binds and blocks

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Chapter 4 Neural Conduction and Synaptic Transmission How Neurons Send and Receive Signals This multimedia product and its contents are protected under copyright law. The following are prohibited by law: • any public performance or display, including transmission of any image over a network; • preparation of any derivative work, including the extraction, in whole or in part, of any images; • any rental, lease, or lending of the program. Copyright © 2006 by Allyn and Bacon

The Neuron’s Resting Membrane Potential l l Inside of the neuron is negative with respect to the outside Resting membrane potential is about -70 m. V Membrane is polarized, it carries a charge Why? Copyright © 2006 by Allyn and Bacon

Ionic Basis of the Resting Potential l l Ions, charged particles, are unevenly distributed Factors influencing ion distribution • • Homogenizing Factors contributing to uneven distribution Copyright © 2006 by Allyn and Bacon

Ionic Basis of the Resting Potential l Homogenizing • • l Random motion – particles tend to move down their concentration gradient Electrostatic pressure – like repels like, opposites attract Factors contributing to uneven distribution • • Membrane is selectively permeable Sodium-potassium pumps Copyright © 2006 by Allyn and Bacon

Ions Contributing to Resting Potential l l Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-) • • synthesized within the neuron found primarily within the neuron Copyright © 2006 by Allyn and Bacon

Equilibrium Potential l l The potential at which there is no net movement of an ion – the potential it will move to achieve when allowed to move freely Na+ = 120 m. V K+ = -90 m. V Cl- = -70 m. V (same as resting potential) Copyright © 2006 by Allyn and Bacon

The Neuron at Rest l l Na+ is driven in by both electrostatic forces and its concentration gradient K+ is driven in by electrostatic forces and out by its concentration gradient Cl- is at equilibrium Sodium-potassium pump – active force that exchanges 3 Na+ inside for 2 K+ outside Copyright © 2006 by Allyn and Bacon

Something to think about l l What would happen if the membrane’s permeability to Na+ were increased? What would happen if the membrane’s permeability to K+ were increased? Copyright © 2006 by Allyn and Bacon

Generation and Conduction of Postsynaptic Potentials (PSPs) l l Neurotransmitters bind at postsynaptic receptors These chemical messengers bind and cause electrical changes • • Depolarizations (making the membrane potential less negative) Hyperpolarizations (making the membrane potential more negative) Copyright © 2006 by Allyn and Bacon

Generation and Conduction of Postsynaptic Potentials (PSPs) l l Postsynaptic depolarizations = Excitatory PSPs (EPSPs) Postsynaptic hyperpolarizations = Inhibitory PSPs (IPSPs) EPSPs make it more likely a neuron will fire, IPSPs make it less likely PSPs are graded potentials – their size varies Copyright © 2006 by Allyn and Bacon

EPSPs and IPSPs l l l Travel passively from their site of origination Decremental – they get smaller as they travel 1 EPSP typically will not suffice to cause a neuron to “fire” and release neurotransmitter – summation is needed Copyright © 2006 by Allyn and Bacon

Integration of PSPs and Generation of Action Potentials (APs) l l In order to generate an AP (or “fire”), the threshold of activation must be reached at the axon hillock Integration of IPSPs and EPSPs must result in a potential of about -65 m. V in order to generate an AP Copyright © 2006 by Allyn and Bacon

Integration l l l Adding or combining a number of individual signals into one overall signal Temporal summation – integration of events happening at different times Spatial - integration of events happening at different places Copyright © 2006 by Allyn and Bacon

What type of summation occurs when: l l One neuron fires rapidly? Multiple neurons fire at the same time? Several neurons fire repeatedly? Both temporal and spatial summation occur simultaneously Copyright © 2006 by Allyn and Bacon

The Action Potential l l All-or-none, when threshold is reached the neuron “fires” and the action potential either occurs or it does not. When threshold is reached, voltageactivated ion channels are opened. Copyright © 2006 by Allyn and Bacon

The Ionic Basis of Action Potentials l l l When summation at the axon hillock results in the threshold of excitation (-65 m. V) being reached, voltage-activated Na+ channels open and sodium rushes in. Remember, all forces were acting to move Na+ into the cell. Membrane potential moves from -70 to +50 m. V. Copyright © 2006 by Allyn and Bacon

The Ionic Basis of Action Potentials l l l Rising phase: Na+ moves membrane potential from -70 to +50 m. V. End of rising phase: After about 1 millisec, Na+ channels close. Change in membrane potential opens voltage-activated K+ channels. Repolarization: Concentration gradient and change in charge leads to efflux of K+. Hyperpolaization: Channels close slowly - K+ efflux leads to membrane potential <-70 m. V. Copyright © 2006 by Allyn and Bacon

$Refractory Periods l l l Absolute – impossible to initiate another action potential Relative$

Refractory Periods l l l Absolute – impossible to initiate another action potential Relative – harder to initiate another action potential Prevent the backwards movement of APs and limit the rate of firing Copyright © 2006 by Allyn and Bacon

The action potential in action l l http: //intro. bio. umb. edu/111112/112 s 99 Lect/neuro_anims/a_p_anim 1/WW 1. htm http: //bio. winona. msus. edu/berg/ANIMT NS/actpot. htm Copyright © 2006 by Allyn and Bacon

PSPs Vs Action Potentials (APs) l l EPSPs/IPSPs Decremental Fast Passive (energy is not used) l l Action Potentials Nondecremental Conducted more slowly than PSPs Passive and active Copyright © 2006 by Allyn and Bacon

Conduction in Myelinated Axons l l Passive movement of AP within myelinated portions occurs instantly Nodes of Ranvier (unmyelinated) • • • Where ion channels are found Where full AP is seen AP appears to jump from node to node • Saltatory conduction • http: //www. brainviews. com/ab. Files/Ani. Salt. htm Copyright © 2006 by Allyn and Bacon

Structure of Synapses l Most common l Dendrodendritic – capable of transmission in either direction Axoaxonal – may be involved in presynaptic inhibition l • Axodendritic – axons on dendrites • Axosomatic – axons on cell bodies Copyright © 2006 by Allyn and Bacon

Synthesis, Packaging, and Transport of Neurotransmitter (NT) l NT molecules • Small • Synthesized in the terminal button and packaged in synaptic vesicles • Large • Assembled in the cell body, packaged in vesicles, and then transported to the axon terminal Copyright © 2006 by Allyn and Bacon

Release of NT Molecules l l Exocytosis – the process of NT release The arrival of an AP at the terminal opens voltage-activated Ca++ channels. The entry of Ca++ causes vesicles to fuse with the terminal membrane and release their contents http: //www. tvdsb. on. ca/westmin/science/ sbioac/homeo/synapse. htm Copyright © 2006 by Allyn and Bacon

Activation of Receptors by NT l l Released NT produces signals in postsynaptic neurons by binding to receptors. Receptors are specific for a given NT. Ligand – a molecule that binds to another. A NT is a ligand of its receptor. Copyright © 2006 by Allyn and Bacon

Receptors l l l There are multiple receptor types for a given NT. Ionotropic receptors – associated with ligand-activated ion channels. Metabotropic receptors – associated with signal proteins and G proteins. Copyright © 2006 by Allyn and Bacon

Ionotropic Receptors l l l NT binds and an associated ion channel opens or closes, causing a PSP. If Na+ channels are opened, for example, an EPSP occurs. If K+ channels are opened, for example, an IPSP occurs. Copyright © 2006 by Allyn and Bacon

Metabotropic Receptors l l Effects are slower, longer-lasting, more diffuse, and more varied. NT (1 st messenger) binds > G protein subunit breaks away > ion channel opened/closed OR a 2 nd messenger is synthesized > 2 nd messengers may have a wide variety of effects Copyright © 2006 by Allyn and Bacon

Reuptake, Enzymatic Degradation, and Recycling l l l As long as NT is in the synapse, it is active – activity must somehow be turned off. Reuptake – scoop up and recycle NT. Enzymatic degradation – a NT is broken down by enzymes. Copyright © 2006 by Allyn and Bacon

Small-molecule Neurotransmitters l l Amino acids – the building blocks of proteins Monoamines – all synthesized from a single amino acid Soluble gases Acetylcholine (ACh) – activity terminated by enzymatic degradation Copyright © 2006 by Allyn and Bacon

Amino Acid Neurotransmitters l l Usually found at fast-acting directed synapses in the CNS Glutamate – Most prevalent excitatory neurotransmitter in the CNS GABA – • synthesized from glutamate • Most prevalent inhibitory NT in the CNS Aspartate and glycine Copyright © 2006 by Allyn and Bacon

Monoamines l l l Effects tend to be diffuse Catecholamines – synthesized from tyrosine • • • Dopamine Norepinephrine Epinephrine Indolamines – synthesized from tryptophan • Serotonin Copyright © 2006 by Allyn and Bacon

Soluble-Gases and ACh l l Soluble gases – exist only briefly • • Nitric oxide and carbon monoxide Retrograde transmission – backwards communication Acetylcholine (Ach) • • Acetyl group + choline Neuromuscular junction Copyright © 2006 by Allyn and Bacon

Neuropeptides l l Large molecules Example – endorphins • “Endogenous opiates” • Produce analgesia (pain suppression) • Receptors were identified before the natural ligand was Copyright © 2006 by Allyn and Bacon

Pharmacology of Synaptic Transmission l Many drugs act to alter neurotransmitter activity • Agonists – increase or facilitate activity • Antagonists – decrease or inhibit activity • A drug may act to alter neurotransmitter activity at any point in its “life cycle” Copyright © 2006 by Allyn and Bacon

Agonists – 2 examples l Cocaine - catecholamine agonist • Blocks reuptake – preventing the activity of the neurotransmitter from being “turned off” l Benzodiazepines - GABA agonists • Binds to the GABA molecule and increases the binding of GABA Copyright © 2006 by Allyn and Bacon

Antagonists – 2 examples l l Atropine – ACh antagonist • Binds and blocks muscarinic receptors • Many of these metabotropic receptors are in the brain • High doses disrupt memory Curare - ACh antagonist • Bind and blocks nicotinic receptors, the ionotropic receptors at the neuromuscular junction • Causes paralysis Copyright © 2006 by Allyn and Bacon