Pinel basics ch03

Copyright © 2007 by Allyn and Bacon

Chapter 3Neural Activity and How to Study ItHow Neurons Work

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Parkinson’s Disease

The case of Mr. d’Orta demonstrates the importance of understanding how neurons work

A lack of dopamine underlies this movement disorder, but it can’t be treated with dopamine

Why not?


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

Sodium, potassium, and chloride ions are the main ones to be concerned with

There are more negative charges inside the neuron than there are outside


Why is there greater negative charge inside? Two properties of the neural membrane

contribute to the differenceDifferential permeability – some substances

pass through the membrane more easily than others, moving through ion channels that can open and close

Sodium potassium pumps – move positively charged sodium ions out, while moving fewer positively charged potassium ions in


Sodium

There is great pressure on sodium to move into the resting neuron

Positively charged sodium is attracted to the internal negative charge

Random motion – as there is more sodium out than in, sodium tends to leak in


Figure 3.1 (NEW)


Postsynaptic Potentials and Action Potentials Neurotransmitters bind at postsynaptic

receptors These chemical messengers bind and

cause electrical changesDepolarizations (making the membrane

potential less negative)Hyperpolarizations (making the membrane

potential more negative)


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

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

Like a gun, it either fires or it does not


Sodium Ions and Action Potentials

When summation results in the threshold of excitation (-65mV) being reached, voltage-activated sodium channels open and sodium rushes in

Remember, at rest, all forces act to move sodium into the cell

Membrane potential moves from -70 to about +50mV, a considerable depolarization


Figure 3.5 (4.6)


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


Axonal Conduction of Action Potentials (APs) The AP travels passively along the axonal

membrane until it reaches an area with voltage-gated sodium channels

Opening sodium channels is an active process that then leads to a new action potential

This new action potential then travels passively to the next area of voltage-gated sodium channels

This process is repeated again and again


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 foundWhere full AP is seenAP appears to jump from node to node

Saltatory conduction


Conduction in Neurons without Axons Many neurons in mammalian

brains do not have axons Neural conduction is typically by

graded, decrementally conducted potentials


Structure of Synapses

Most commonAxodendritic – axons on dendritesAxosomatic – axons on cell bodies

Directed – release and binding sites are close

Nondirected – release and binding sites are at some distance


Synthesis and Transport of Neurotransmitter (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 terminalPeptides – chains of amino acids

Coexistence – many neurons contain both small-molecule and large-molecule NT


Release of NT Molecules

Exocytosis – the process of NT release The arrival of an AP at the terminal opens

voltage-activated calcium channels The entry of calcium causes vesicles to

fuse with the terminal membrane and release their contents


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 sodium channels are opened, for example, an EPSP occurs due to the entry of sodium


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



Autoreceptors

Metabotropic receptorsBind to their neuron’s own NT moleculesLocated on the presynaptic membrane

Usually monitor the number of neurotransmitter molecules on the synapse


Termination of NT Effects

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 enzymesExample - acetylcholinesterase


The Neurotransmitters

Four classes of small-molecule NT One large-molecule variety –

peptides or neuropeptides Most NT produce either excitation or

inhibition, but some may do both by having different effects at different receptor subtypes


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 glutamateMost prevalent inhibitory NT in the CNS

Aspartate and glycine


Monoamines

Effects tend to be diffuse Catecholamines – synthesized from

tyrosineDopamineNorepinephrineEpinephrine

Indolamines – synthesized from tryptophanSerotonin


Soluble-Gases and ACh

Soluble gases – exist only brieflyNitric oxide and carbon monoxideRetrograde transmission – backwards

communication Acetylcholine (Ach)

Acetyl group + choline Neuromuscular junction


Neuropeptides

Large molecules, close to 100 identified

Example – endorphins“Endogenous opiates”Produce analgesia (pain suppression)Receptors were identified before the

natural ligand was


How Biopsychologists Study the Brain

Stereotaxic surgery Conventional, lesion, stimulation, and

recording methods Pharmacological methods Brain imaging Genetic engineering


Stereotaxic Surgery

Used to position experimental devices within the brain

Stereotaxic atlas – provides coordinates for locating structures within the brain

Bregma – a point on the top of the skull often used as a reference point

Sterotaxic instrument – used to hold head steady and guide the device to be inserted



Lesion Methods

Lesion (or destroy) a structure to observe the effect on behavior

Electrolytic lesion – electrical current used to destroy the target structure

Aspiration lesions – suction - cortex Knife cuts – may damage surrounding

area



Stimulation Methods

Conventional methods involve using brain stimulation to determine the effects of a given brain structure

Current is delivered used a permanently implanted electrode

Rarely used in humans


Recording Methods

Unit recording – recording the activity of individual neurons

Multiple-unit recording – recording the overall firing rate of many neurons in an area

EEG – electrodes on the scalp record the difference between 2 large electrodes



Pharmacological Methods

Many drugs act to alter NT activity Agonists – increase or facilitate Antagonists – decrease or inhibit Drugs may act to alter NT activity at

any point, from synthesis to termination




Agonist - Example

Cocaine - catecholamine agonist Blocks reuptake – preventing the

activity of the neurotransmitter from being “turned off”

Cocaine causes dopamine and norepinephrine to remain active in the synapse for a longer period of time


Acetylcholine Antagonists

Curare – Binds and blocks nicotinic receptors, the ionotropic receptors at the neuromuscular junctionCauses paralysis

Botox – Blocks release of acetylcholine at the neuromuscular junctionA deadly poison Minute doses at specific places, however, has

medical and cosmetic uses


Selective Chemical Lesions

Neural poisons (neurotoxins) selectively target specific nervous system components

Kainic acid – destroys cell bodies 6-hydroxydopamine (6-OHDA) –

destroys noradrenergic and dopaminergic neurons


Brain Imaging

Contrast X-Rays – inject something that absorbs X-rays less or more than surrounding tissueCerebral angiography

X-Ray Computed Tomography (CT)2-D images combined to create a 3-D one

Magnetic Resonance Imaging (MRI)Produces 3-D images with high spatial

resolution


Brain Imaging

Positron Emission Tomography (PET) Inject radioactive 2-DG

Functional MRI (fMRI)Visualizing oxygen flow in the brain Currently the predominant brain

recording technique of cognitive neuroscience


fMRI Vs PET

Nothing injected. Provides both structural and functional

information in one image Spatial resolution is better than with PET Can create 3-D images of activity over the

entire brain


Weaknesses of fMRI

To create an fMRI image, brain activity from many subjects is needed and there are differences among people

Not able to detect small areas of brain activity

Only infers neural activity from changes in blood flow


Genetic Engineering

Gene knockout techniquesSubjects missing a given gene can provide

insight into what the gene controlsDifficult to interpret results – most behavior is

controlled by many genes and removing one gene may alter the expression of others

Gene replacement techniques Both are currently being intensely studied

Pinel basics ch03

Technology