Chapter 4Neural Conduction and Synaptic TransmissionHow Neurons Send and

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The Neuron’s Resting Membrane Potential

Inside of the neuron is negative with respect to the outside

Resting membrane potential is about -70mV

Membrane is polarized, it carries a charge

Why?

Ionic Basis of the Resting Potential

Ions, charged particles, are unevenly distributed

Factors influencing ion distribution• Homogenizing

• Factors contributing to uneven distribution

Ionic Basis of the Resting Potential

Homogenizing• 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

Ions Contributing to Resting Potential

Sodium (Na+) Chloride (Cl-) Potassium (K+) Negatively charged proteins (A-)

• synthesized within the neuron

• found primarily within the neuron

The Neuron at Rest

Ions move in and out through ion-specific channels

K+ and Cl- pass readily Little movement of Na+ A- don’t move at all, trapped inside

Equilibrium Potential

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+ = 120mV K+ = -90mV Cl- = -70mV (same as resting potential)

The Neuron at Rest 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

Something to think about

What would happen if the membrane’s permeability to Na+ were increased?

What would happen if the membrane’s permeability to K+ were increased?

Generation and Conduction of Postsynaptic Potentials (PSPs)

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)

Generation and Conduction of Postsynaptic Potentials (PSPs) 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

EPSPs and IPSPs

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

Integration of PSPs and Generation of Action Potentials (APs)

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 -65mV in order to generate an AP

Integration

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

What type of summation occurs when:

One neuron fires rapidly? Multiple neurons fire at the same time? Several neurons fire repeatedly? Both temporal and spatial summation

occur simultaneously

The Action Potential

All-or-none, when threshold is reached the neuron “fires” and the action potential either occurs or it does not.

When threshold is reached, voltage-activated ion channels are opened.

The Ionic Basis of Action Potentials

When summation at the axon hillock results in the threshold of excitation (-65mV) 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 +50mV.

The Ionic Basis of Action Potentials

Rising phase: Na+ moves membrane potential from -70 to +50mV.

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 <-70mV.

Refractory Periods

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

The action potential in action

http://intro.bio.umb.edu/111-112/112s99Lect/neuro_anims/a_p_anim1/WW1.htm

http://bio.winona.msus.edu/berg/ANIMTNS/actpot.htm

PSPs Vs Action Potentials (APs)

EPSPs/IPSPs Decremental Fast Passive (energy is

not used)

Action Potentials Nondecremental Conducted more

slowly than PSPs Passive and active

Conduction in Myelinated Axons

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/abFiles/AniSalt.htm

Structure of Synapses

Most common• Axodendritic – axons on dendrites

• Axosomatic – axons on cell bodies Dendrodendritic – capable of

transmission in either direction Axoaxonal – may be involved in

presynaptic inhibition

Synthesis, Packaging, and Transport of Neurotransmitter (NT)

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

Release of NT Molecules 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

Activation of Receptors by NT

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.

Receptors

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.

Ionotropic Receptors

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.

Metabotropic Receptors

Effects are slower, longer-lasting, more diffuse, and more varied.

NT (1st messenger) binds > G protein subunit breaks away > ion channel opened/closed OR a 2nd messenger is synthesized > 2nd messengers may have a wide variety of effects

Reuptake, Enzymatic Degradation, and Recycling

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.

Small-molecule Neurotransmitters

Amino acids – the building blocks of proteins

Monoamines – all synthesized from a single amino acid

Soluble gases Acetylcholine (ACh) – activity terminated

by enzymatic degradation

Amino Acid Neurotransmitters

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

Monoamines

Effects tend to be diffuse Catecholamines – synthesized from tyrosine

• Dopamine

• Norepinephrine

• Epinephrine Indolamines – synthesized from tryptophan

• Serotonin

Soluble-Gases and ACh

Soluble gases – exist only briefly• Nitric oxide and carbon monoxide

• Retrograde transmission – backwards communication

Acetylcholine (Ach)• Acetyl group + choline

• Neuromuscular junction

Neuropeptides

Large molecules Example – endorphins

• “Endogenous opiates”

• Produce analgesia (pain suppression)

• Receptors were identified before the natural ligand was

Pharmacology of Synaptic Transmission

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”

Agonists – 2 examples

Cocaine - catecholamine agonist• Blocks reuptake – preventing the activity of

the neurotransmitter from being “turned off” Benzodiazepines - GABA agonists

• Binds to the GABA molecule and increases the binding of GABA

Antagonists – 2 examples 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