Chapter 11 AMP

Nervous system

is master controlling and communicating system of body

• Cells communicate via electrical and chemical signals

– Rapid and specific

– Usually cause almost immediate responses

Nervous system has three overlapping functions

1. Sensory input

 Information gathered by sensory receptors about internal and external

changes

2. Integration

 Processing and interpretation of sensory input

3. Motor output

 Activation of effector organs (muscles and glands) produces a response

Nervous system is divided into two principal parts

Central nervous system (CNS)

 Brain and spinal cord of dorsal body cavity

 Integration and control center

– Interprets sensory input and dictates motor output

– Peripheral nervous system (PNS)

 The portion of nervous system outside CNS

 Consists mainly of nerves that extend from brain and spinal cord

– Spinal nerves to and from spinal cord

– Cranial nerves to and from brain

Peripheral nervous system (PNS) has two functional divisions

Sensory (afferent) division

 Somatic sensory fibers: convey impulses from skin, skeletal muscles, and

joints to CNS

 Visceral sensory fibers: convey impulses from visceral organs to CNS

– Motor (efferent) division

 Transmits impulses from CNS to effector organs

– Muscles and glands

 Two divisions

– Somatic nervous system

– Autonomic nervous system

Somatic nervous system

Somatic motor nerve fibers conduct impulses from CNS to skeletal muscle

– Voluntary nervous system

 Conscious control of skeletal muscles

Autonomic nervous system

Consists of visceral motor nerve fibers

– Regulates smooth muscle, cardiac muscle, and glands

– Involuntary nervous system

– Two functional subdivisions

 Sympathetic

 Parasympathetic

 Work in opposition to each other

Nervous tissue histology

• Nervous tissue consists of two principal cell types

Neuroglia (glial cells): small cells that surround and wrap delicate neurons

– Neurons (nerve cells): excitable cells that transmit electrical signals

Four main neuroglia support CNS neurons

Astrocytes

– Microglial cells

– Ependymal cells

– Oligodendrocytes

Astrocytes

Most abundant, versatile, and highly branched of glial cells

– Cling to neurons, synaptic endings, and capillaries

Functions include:

 Support and brace neurons

 Play role in exchanges between capillaries and neurons

 Guide migration of young neurons

 Control chemical environment around neurons

 Respond to nerve impulses and neurotransmitters

 Influence neuronal functioning

 Participate in information processing in brain

Neuroglia of the CNS (4 of 6)

• Microglial cells

Small, ovoid cells with thorny processes that touch and monitor neurons

– Migrate toward injured neurons

– Can transform to phagocytize microorganisms and neuronal debris

Neuroglia of the CNS (5 of 6)

• Ependymal cells

Range in shape from squamous to columnar

– May be ciliated

 Cilia beat to circulate CSF

– Line the central cavities of the brain and spinal column

– Form permeable barrier between cerebrospinal fluid (CSF) in cavities and tissue

fluid bathing CNS cells

Neuroglia of the CNS (6 of 6)

• Oligodendrocytes

Branched cells

– Processes wrap CNS nerve fibers, forming insulating myelin sheaths in thicker

nerve fibers

Neuroglia of PNS

• Two major neuroglia seen in PNS

Satellite cells

– Surround neuron cell bodies in PNS

– Function similar to astrocytes of CNS

• Schwann cells (neurolemmocytes)

– Surround all peripheral nerve fibers and form myelin sheaths in thicker nerve fibers

 Similar function as oligodendrocytes

– Vital to regeneration of damaged peripheral nerve fibers

Neurons

(nerve cells) are structural units of nervous system

• Large, highly specialized cells that conduct impulses

• Special characteristics

– Extreme longevity (lasts a person’s lifetime)

– Amitotic, with few exceptions

– High metabolic rate: requires continuous supply of oxygen and glucose

• All have cell body and one or more processes

Neuron Cell Body

Also called the perikaryon or soma

• Biosynthetic center of neuron

– Synthesizes proteins, membranes, chemicals

– Rough ER (chromatophilic substance, or Nissl bodies)

• Contains spherical nucleus with nucleolus

• Some contain pigments

• In most, plasma membrane is part of receptive region that receives input info from other

neurons

Most neuron cell bodies are located in CNS

– Nuclei: clusters of neuron cell bodies in CNS

– Ganglia: clusters of neuron cell bodies in PNS

Neuron Processes

Armlike processes that extend from cell body

– CNS contains both neuron cell bodies and their processes

– PNS contains chiefly neuron processes

• Tracts

– Bundles of neuron processes in CNS

• Nerves

– Bundles of neuron processes in PNS

• Two types of processes

– Dendrites

– Axon

Dendrites

Motor neurons can contain 100s of these short, tapering, diffusely branched

processes

 Contain same organelles as in cell body

– Receptive (input) region of neuron

– Convey incoming messages toward cell body as graded potentials (short distance

signals)

– In many brain areas, finer dendrites are highly specialized to collect information

 Contain dendritic spines, appendages with bulbous or spiky ends

Neuron Processes (3 of 10)

• The axon: structure

Each neuron has one axon that starts at cone-shaped area called axon hillock

– In some neurons, axons are short or absent; in others, axon comprises almost

entire length of cell

 Some axons can be over 1 meter long

– Long axons are called nerve fibers

– Axons have occasional branches called axon collaterals

– Axons branch profusely at their end (terminus)

 Can number as many as 10,000 terminal branches

– Distal endings are called axon terminals or terminal boutons

The axon: functional characteristics

Axon is the conducting region of neuron

– Generates nerve impulses and transmits them along axolemma (neuron cell

membrane) to axon terminal

 Terminal: region that secretes neurotransmitters, which are released into

extracellular space

 Can excite or inhibit neurons it contacts

– Carries on many conversations with different neurons at same time

– Axons rely on cell bodies to renew proteins and membranes

– Quickly decay if cut or damaged

Axons have efficient internal transport mechanisms

 Molecules and organelles are moved along axons by motor proteins and

cytoskeletal elements

– Movement occurs in both directions

 Anterograde: away from cell body

– Examples: mitochondria, cytoskeletal elements, membrane components,

enzymes

 Retrograde: toward cell body

– Examples: organelles to be degraded, signal molecules, viruses, and

bacterial toxins

Homeostatic Imbalance

Certain viruses and bacterial toxins damage neural tissues by using retrograde axonal

transport

– Example: polio, rabies, and herpes simplex viruses, and tetanus toxin

• Research is under way to investigate using retrograde transport to treat genetic diseases

– Viruses containing “corrected” genes or microRNA to suppress defective genes can

enter cell through retrograde transport

Myelin sheath

Composed of myelin, a whitish, protein-lipid substance

– Function of myelin

 Protect and electrically insulate axon

 Increase speed of nerve impulse transmission

– Myelinated fibers: segmented sheath surrounds most long or large-diameter

axons

– Nonmyelinated fibers: do not contain sheath

 Conduct impulses more slowly

Myelination in the PNS

Formed by Schwann cells

 Wraps around axon in jelly roll fashion

 One cell forms one segment of myelin sheath

– Outer collar of perinuclear cytoplasm (formerly called neurilemma): peripheral

bulge containing nucleus and most of cytoplasm

– Plasma membranes have less protein

 No channels or carriers, so good electrical insulators

 Interlocking proteins bind adjacent myelin membranes

Myelin sheath gaps

 Gaps between adjacent Schwann cells

 Sites where axon collaterals can emerge

 Formerly called nodes of Ranvier

– Nonmyelinated fibers

 Thin fibers not wrapped in myelin; surrounded by Schwann cells but no coiling;

one cell may surround 15 different fibers

Myelin sheaths in the CNS

Formed by processes of oligodendrocytes, not whole cells

– Each cell can wrap up to 60 axons at once

– Myelin sheath gap is present

– No outer collar of perinuclear cytoplasm

– Thinnest fibers are unmyelinated, but covered by long extensions of adjacent

neuroglia

White matter: regions of brain and spinal cord with dense collections of myelinated

fibers

 Usually fiber tracts

– Gray matter: mostly neuron cell bodies and nonmyelinated fibers

Structural classification

– Three types grouped by number of processes

1. Multipolar: three or more processes (1 axon, others dendrites)

– Most common and major neuron type in CNS

2. Bipolar: two processes (one axon, 1one dendrite)

– Rare (ex: retina and olfactory mucosa)

3. Unipolar: one T-like process (two axons)

– Also called pseudounipolar

– Peripheral (distal) process: associated with sensory receptor

– Proximal (central) process: enters CNS

Functional classification of neurons

– Three types of neurons grouped by direction in which nerve impulse travels relative

to CNS

1. Sensory

– Transmit impulses from sensory receptors toward CNS

– Almost all are unipolar

– Cell bodies are located in ganglia in PNS

2. Motor

– Carry impulses from CNS to effectors

– Multipolar

– Most cell bodies are located in CNS (except some autonomic neurons)

3. Interneurons

– Also called association neurons

– Lie between motor and sensory neurons

– Shuttle signals through CNS pathways

– Most are entirely within CNS

– 99% of body’s neurons are interneurons

Voltage

a measure of potential energy generated by separated charge

 Measured between two points in volts (V) or millivolts (mV)

 Called potential difference or potential

– Charge difference across plasma membrane results in potential

 Greater charge difference between points = higher voltage

Current

flow of electrical charge (ions) between two points

 Can be used to do work

 Flow is dependent on voltage and resistance

Resistance

hindrance to charge flow

 Insulator: substance with high electrical resistance

 Conductor: substance with low electrical resistance

Ohm’s law

gives relationship of voltage, current, resistance

Current (I)  voltage (V)/resistance (R)

– Current is directly proportional to voltage

 Greater the voltage (potential difference), greater the current

 No net current flow between points with same potential

– Current is inversely proportional to resistance

 The greater the resistance, the smaller the current

Role of membrane ion channels

Large proteins serve as selective membrane ion channels

 K+ ion channel allows only K+ to pass through

– Two main types of ion channels

 Leakage (nongated) channels, which are always open

 Gated channels, in which part of the protein changes shape to open/close the

channel

– Three main gated channels: chemically gated, voltage—gated, or

mechanically gated

Basic Principles of Electricity

Chemically gated (ligand-gated) channels

– Open only with binding of a specific chemical (example: neurotransmitter)

• Voltage-gated channels

– Open and close in response to changes in membrane potential

• Mechanically gated channels

– Open and close in response to physical deformation of receptors, as in sensory

receptors

When gated channels are open, ions diffuse quickly:

– Along chemical concentration gradients from higher concentration to lower

concentration

– Along electrical gradients toward opposite electrical charge

Electrochemical gradient

electrical and chemical gradients combined

• Ion flow creates an electrical current, and voltage changes across membrane

– Expressed by rearranged Ohm’s law equation:

V = IR

Resting membrane potential

of a resting neuron is approximately 70 mV

– The cytoplasmic side of membrane is negatively charged relative to the outside

– The actual voltage difference varies from

40 mV to 90 mV

– The membrane is said to be polarized

Potential generated by

Differences in ionic composition of ICF and ECF

– Differences in plasma membrane permeability

Differences in ionic composition

ECF has higher concentration of Na+than ICF

 Balanced chiefly by chloride ions (Cl)

– ICF has higher concentration of K+ than ECF

 Balanced by negatively charged proteins

– K+ plays most important role in membrane potential

Resting Membrane Potential

Generating a resting membrane potential depends on (1) differences in K+ and

Na+concentrations inside and outside cells, and (2) differences in permeability of the

plasma membrane to these ions.

Differences in plasma membrane permeability

– Impermeable to large anionic proteins

– Slightly permeable to Na+(through leakage channels)

 Sodium diffuses into cell down concentration gradient

– 25 times more permeable to K+ than sodium (more leakage channels)

 Potassium diffuses out of cell down concentration gradient

– Quite permeable to Cl–

More potassium diffuses out than sodium diffuses in

 As a result, the inside of the cell is more negative

 Establishes resting membrane potential

Sodium-potassium pump (Na+K+ ATPase)

stabilizes resting membrane potential

 Maintains concentration gradients for Na+and K+

 Three Na+are pumped out of cell while two K+ are pumped back in

Changing the Resting Membrane Potential

Membrane potential changes when:

– Concentrations of ions across membrane change

– Membrane permeability to ions changes

• Changes produce two types of signals

– Graded potentials

 Incoming signals operating over short distances

– Action potentials

 Long-distance signals of axons

• Changes in membrane potential are used as signals to receive, integrate, and send

information

Terms describing membrane potential changes relative to resting membrane potential

Depolarization: decrease in membrane potential (moves toward zero and above)

 Inside of membrane becomes less negative than resting membrane potential

 Probability of producing impulse increases

– Hyperpolarization: increase in membrane potential (away from zero)

 Inside of membrane becomes more negative than resting membrane potential

 Probability of producing impulse decreases

Graded Potentials

Short-lived, localized changes in membrane potential

– The stronger the stimulus, the more voltage changes and the farther current flows

• Triggered by stimulus that opens gated ion channels

– Results in depolarization or sometimes hyperpolarization

• Named according to location and function

– Receptor potential (generator potential): graded potentials in receptors of sensory

neurons

– Postsynaptic potential: neuron graded potential

Action Potentials

Principal way neurons send signals

– Means of long-distance neural communication

• Occur only in muscle cells and axons of neurons

• Brief reversal of membrane potential with a change in voltage of ~100 mV

• Action potentials (APs) do not decay over distance as graded potentials do

• In neurons, also referred to as a nerve impulse

• Involves opening of specific voltage-gated channels

Generating an Action Potential (1 of 5)

• Four main steps

1. Resting state: All gated Na+and K+ channels are closed

 Only leakage channels for Na+ and K+ are open

– Maintains the resting membrane potential

 Each Na+ channel has two voltage-sensitive gates

– Activation gates: closed at rest; open with depolarization, allowing Na+ to

enter cell

– Inactivation gates: open at rest; block channel once it is open to prevent

more Na+ from entering cell

 Each K+ channel has one voltage-sensitive gate

– Closed at rest

– Opens slowly with depolarization

Generating an Action Potential (2 of 5)

2. Depolarization: Na+ channels open

Depolarizing local currents open voltage-gated Na+channels, and Na+ rushes

into cell

 Na+activation and inactivation gates open

 Na+influx causes more depolarization, which opens more Na+channels

– As a result, ICF becomes less negative

 At threshold (–55 to –50 mV), positive feedback causes opening of all

Na+channels

– Results in large action potential spike

– Membrane polarity jumps to +30 mV

Generating an Action Potential (3 of 5)

3. Repolarization: Na+channels are inactivating, and K+ channels open

Na+ channel inactivation gates close

– Membrane permeability to Na+declines to resting state

– AP spike stops rising

 Voltage-gated K+ channels open

– K+ exits cell down its electrochemical gradient

 Repolarization: membrane returns to resting membrane potential

Generating an Action Potential (4 of 5)

4. Hyperpolarization: Some K+ channels remain open, and Na+channels reset

Some K+ channels remain open, allowing excessive K+ efflux

– Inside of membrane becomes more negative than in resting state

 This causes hyperpolarization of the membrane (slight dip below resting

voltage)

 Na+ channels also begin to reset

Repolarization resets electrical conditions, not ionic conditions

• After repolarization, Na+/K+ pumps (thousands of them in an axon) restore ionic

conditions

Threshold and the All-or-None Phenomenon

Not all depolarization events produce APs

• For an axon to “fire,” depolarization must reach threshold voltage to trigger AP

• At threshold:

– Membrane is depolarized by 15 to 20 mV

– Na+ permeability increases

– Na+ influx exceeds K+ efflux

– The positive feedback cycle begins

• All-or-None: An AP either happens completely, or does not happen at all

Propagation of an Action Potential

Propagation allows AP to be transmitted from origin down entire axon length toward

terminals

• Na+ influx through voltage gates in one membrane area cause local currents that cause

opening of Na+ voltage gates in adjacent membrane areas

– Leads to depolarization of that area, which in turn causes depolarization in next

area

Once initiated, an AP is self-propagating

– In nonmyelinated axons, each successive segment of membrane depolarizes, then

repolarizes

– Propagation in myelinated axons differs

• Since Na+ channels closer to the AP origin are still inactivated, no new AP is generated

there

– AP occurs only in a forward direction

Coding for Stimulus Intensity

All action potentials are alike and are independent of stimulus intensity

• CNS tells difference between a weak stimulus and a strong one by frequency of

impulses

– Frequency is number of impulses (APs) received per second

– Higher frequencies mean stronger stimulus

Refractory Periods

Refractory period: time in which neuron cannot trigger another AP

– Voltage-gated Na+ channels are open, so neuron cannot respond to another

stimulus

• Two types

– Absolute refractory period

 Time from opening of Na+channels until resetting of the channels

 Ensures that each AP is an all-or-none event

 Enforces one-way transmission of nerve impulses

Relative refractory period

 Follows absolute refractory period

– Most Na+channels have returned to their resting state

– Some K+ channels still open

– Repolarization is occurring

 Threshold for AP generation is elevated

 Only exceptionally strong stimulus could stimulate an AP

– Think of a disobedient (refractory) dog – if he is absolutely refractory he will never

come when called, but if he is relatively refractory, he may come but only if you call

loud enough

Conduction Velocity

APs occur only in axons, not other cell areas

• AP conduction velocities in axons vary widely

• Rate of AP propagation depends on two factors:

1. Axon diameter

 Larger-diameter fibers have less resistance to local current flow, so have faster

impulse conduction

2. Degree of myelination

 Two types of conduction depending on presence or absence of myelin

– Continuous conduction

– Saltatory conduction

Continuous conduction: slow conduction that occurs in nonmyelinated axons

– Saltatory conduction: occurs only in myelinated axons and is about 30 times

faster

 Myelin sheaths insulate and prevent leakage of charge

 Voltage-gated Na+ channels are located at myelin sheath gaps

 APs generated only at gaps

 Electrical signal appears to jump rapidly from gap to gap

Clinical–Homeostatic Imbalance 11.2

Multiple sclerosis (MS) is an autoimmune disease that affects primarily young adults

• Myelin sheaths in CNS are destroyed when immune system attacks myelin

– Turns myelin into hardened lesions called scleroses

– Impulse conduction slows and eventually ceases

– Demyelinated axons increase Na+channels, causing cycles of relapse and

remission

Symptoms: visual disturbances, weakness, loss of muscular control, speech

disturbances, incontinence

• Treatment: drugs that modify immune system activity

• May not be able to prevent, but maintaining high blood levels of vitamin D may reduce

risk of development

Nerve fibers are classified according to diameter, degree of myelination, and speed of

conduction

• Fall into three groups:

– Group A fibers

 Largest diameter

 Myelinated somatic sensory and motor fibers of skin, skeletal muscles, and

joints

 Transmit at 150 m/s (~300 mph)

Group B fibers

 Intermediate diameter

 Lightly myelinated fibers

 Transmit at 15 m/s (~30 mph)

– Group C fibers

 Smallest diameter

 Unmyelinated

 Transmit at 1 m/s (~2 mph)

– B and C groups include ANS visceral motor and sensory fibers that serve visceral

organs

Clinical–Homeostatic Imbalance 1

Impaired AP impulse propagation can be caused by a number of chemical and physical

factors.

• Local anesthetics act by blocking voltage-gated Na+channels.

• Cold temperatures or continuous pressure interrupt blood circulation and delivery of

oxygen to neurons

– Cold fingers get numb, or foot “goes to sleep”

The Synapse

Nervous system works because information flows from neuron to neuron

• Neurons are functionally connected by synapses, junctions that mediate information

transfer

– From one neuron to another neuron

– Or from one neuron to an effector cell

Presynaptic neuron: neuron conducting impulses toward synapse (sends information)

• Postsynaptic neuron: neuron transmitting electrical signal away from synapse

(receives information)

– In PNS may be a neuron, muscle cell, or gland cell

• Most function as both

Synapses

Synaptic connections

– Axodendritic: between axon terminals of one neuron and dendrites of others

– Axosomatic: between axon terminals of one neuron and soma (cell body) of

others

– Less common connections:

 Axoaxonal (axon to axon)

 Dendrodendritic (dendrite to dendrite)

 Somatodendritic (dendrite to soma)

– Two main types of synapses:

 Chemical synapse

 Electrical synapse

Chemical Synapses

Most common type of synapse

• Specialized for release and reception of chemical neurotransmitters

• Typically composed of two parts

– Axon terminal of presynaptic neuron: contains synaptic vesicles filled with

neurotransmitter

– Receptor region on postsynaptic neuron’s membrane: receives neurotransmitter

 Usually on dendrite or cell body

– Two parts separated by fluid-filled synaptic cleft

• Electrical impulse changed to chemical across synapse, then back into electrical

Transmission across synaptic cleft

– Synaptic cleft prevents nerve impulses from directly passing from one neuron to

next

– Chemical event (as opposed to an electrical one)

– Depends on release, diffusion, and receptor binding of neurotransmitters

– Ensures unidirectional communication between neurons

Chemical Synapses (3

Information transfer across chemical synapses

– Six steps are involved:

1. AP arrives at axon terminal of presynaptic neuron

2. Voltage-gated Ca2+channels open, and Ca2+

enters axon terminal

– Ca2+ flows down electrochemical gradient from ECF to inside of axon

terminal

3. Ca2+ entry causes synaptic vesicles to release neurotransmitter

– Ca2+ causes synaptotagmin protein to react with SNARE proteins that

control fusion of synaptic vesicles with axon membrane

– Fusion results in exocytosis of neurotransmitter into synaptic cleft

– The higher the impulse frequency, the more vesicles exocytose, leading

to a greater effect on the postsynaptic cell

4. Neurotransmitter diffuses across the synaptic cleft and binds to specific

receptors on the postsynaptic membrane

– Often chemically gated ion channels

5. Binding of neurotransmitter opens ion channels, creating graded

potentials

– Binding causes receptor protein to change shape, which causes ion

channels to open

• Causes a graded potential in postsynaptic cell

• Can be an excitatory or inhibitory event

• Some receptor proteins are also ion channels

6. Neurotransmitter effects are terminated

– As long as neurotransmitter is binding to receptor, graded potentials will

continue, so process needs to be regulated

– Within a few milliseconds, neurotransmitter effect is terminated in one of

three ways

• Reuptake by astrocytes or axon terminal

• Degradation by enzymes

• Diffusion away from synaptic cleft

Synaptic delay

Time needed for neurotransmitter to be released, diffuse across synapse, and bind

to receptors

 Can take anywhere from 0.3 to 5.0 ms

– Synaptic delay is rate-limiting step of neural transmission

 Transmission of AP down axon can be very quick, but synapse slows

transmission to postsynaptic neuron down significantly

 Not noticeable, because these are still very fast

Electrical Synapses

Less common than chemical synapses

• Neurons are electrically coupled

– Joined by gap junctions that connect cytoplasm of adjacent neurons

– Communication is very rapid and may be unidirectional or bidirectional

– Found in some brain regions responsible for eye movements or hippocampus in

areas involved in emotions and memory

– Most abundant in embryonic nervous tissue

Postsynaptic Potentials

Neurotransmitter receptors cause graded potentials that vary in strength based on:

– Amount of neurotransmitter released

– Time neurotransmitter stays in cleft

• Depending on effect of chemical synapse, there are two types of postsynaptic potentials

– EPSP: excitatory postsynaptic potentials

– IPSP: inhibitory postsynaptic potentials

Excitatory Synapses and EPSPs

Neurotransmitter binding opens chemically gated channels

– Allows simultaneous flow of Na+ and K+ in opposite directions

• Na+ influx greater than K+ efflux, resulting in local net graded potential depolarization

called excitatory postsynaptic potential (EPSP)

• EPSPs trigger AP if EPSP is of threshold strength

– Can spread to axon hillock and trigger opening of voltage-gated channels, causing

AP to be generated

Inhibitory Synapses and IPSPs

Neurotransmitter binding to receptor opens chemically gated channels that allow

entrance/exit of ions that cause hyperpolarization

– Makes postsynaptic membrane more permeable to K+ or Cl–

 If K+ channels open, it moves out of cell

 If Cl– channels open, it moves into cell

– Reduces postsynaptic neuron’s ability to produce an action potential

 Moves neuron farther away from threshold (makes it more negative)

Integration and Modification of Synaptic

Events

Summation by the postsynaptic neuron

– A single EPSP cannot induce an AP, but EPSPs can summate (add together) to

influence postsynaptic neuron

 IPSPs can also summate

– Most neurons receive both excitatory and inhibitory inputs from thousands of other

neurons

 Only if EPSPs predominate and bring to threshold will an AP be generated

– Two types of summations: temporal and spatial

Temporal summation

 One or more presynaptic neurons transmit impulses in rapid-fire order

– First impulse produces EPSP, and before it can dissipate another EPSP

is triggered, adding on top of first impulse

– Spatial summation

 Postsynaptic neuron is stimulated by large number of terminals simultaneously

– Many receptors are activated, each producing EPSPs, which can then

add together

Synaptic potentiation

– Repeated use of synapse increases ability of presynaptic cell to excite

postsynaptic neuron

 Ca2+ concentration increases in presynaptic terminal, causing release of more

neurotransmitter

 Leads to more EPSPs in postsynaptic neuron

– Potentiation can cause Ca2+ voltage gates to open on postsynaptic neuron

 Ca2+ activates kinase enzymes, leading to more effective response to

subsequent stimuli

– Long-term potentiation: learning and memory

Presynaptic inhibition

– Release of excitatory neurotransmitter by one neuron is inhibited by another

neuron via an axoaxonal synapse

– Less neurotransmitter is released, leading to smaller EPSPs

Neurotransmitters

Language of nervous system

• 50 or more neurotransmitters have been identified

• Most neurons make two or more neurotransmitters

– Neurons can exert several influences

• Usually released at different stimulation frequencies

• Classified by:

– Chemical structure

– Function

Classification of Neurotransmitters by

Chemical Structure (1 of 12)

• Acetylcholine (ACh)

– First identified and best understood

– Released at neuromuscular junctions

 Also used by many ANS neurons and some CNS neurons

– Synthesized from acetic acid and choline by enzyme choline acetyltransferase

– Degraded by enzyme acetylcholinesterase (AChE)

Classification of Neurotransmitters by

Chemical Structure (2 of 12)

Biogenic amines

– Catecholamines

 Dopamine, norepinephrine (NE), and epinephrine: made from the amino acid

tyrosine

– Indolamines

 Serotonin: made from the amino acid tryptophan

 Histamine: made from the amino acid histidine

– All widely used in brain: play roles in emotional behaviors and biological clock

– Used by some ANS motor neurons

 Especially NE

– Imbalances are associated with mental illness

Amino acids

– Amino acids make up all proteins: therefore, it is difficult to prove which are

neurotransmitters

– Amino acids that are proven neurotransmitters

 Glutamate

 Aspartate

 Glycine

 GABA: gamma ()-aminobutyric acid

Classification of Neurotransmitters by

Chemical Structure (4

Peptides (neuropeptides)

– Strings of amino acids that have diverse functions

 Substance P

– Mediator of pain signals

 Endorphins

– Beta endorphin, dynorphin, and enkephalins: act as natural opiates;

reduce pain perception

 Gut-brain peptides

– Somatostatin and cholecystokinin play a role in regulating digestion

Purines

– Monomers of nucleic acids that have an effect in both CNS and PNS

 ATP, the energy molecule, is now considered a neurotransmitter

 Adenosine is a potent inhibitor in brain

– Caffeine blocks adenosine receptors

 Can induce Ca2+ influx in astrocytes

Classification of Neurotransmitters by

Chemical Structure (6

Gases and lipids

– Gasotransmitters

 Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H2S)

 Bind with G protein–coupled receptors in brain

 Lipid soluble and are synthesized on demand

 NO involved in learning and formation of new memories, as well as brain

damage in stroke patients, and smooth muscle relaxation in intestine

 H2S acts directly on ion channels to alter function

Endocannabinoids

 Act at same receptors as THC (active ingredient in marijuana)

 Most common G protein–linked receptors in brain

 Lipid soluble

 Synthesized on demand

 Believed to be involved in learning and memory

 May be involved in neuronal development, controlling appetite, and

suppressing nausea

Neurotransmitters exhibit a great diversity of functions

• Functions can be grouped into two classifications:

– Effects

– Actions

Classification of Neurotransmitters by

Chemical Structure (9

Effects: excitatory versus inhibitory

– Neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory

(hyperpolarizing)

– Effect determined by receptor to which it binds

 GABA and glycine are usually inhibitory

 Glutamate is usually excitatory

 Acetylcholine and NE bind to at least two receptor types with opposite effects

– ACh is excitatory at neuromuscular junctions in skeletal muscle

– ACh is inhibitory in cardiac muscle

Actions: direct versus indirect

– Direct action: neurotransmitter binds directly to and opens ion channels

 Promotes rapid responses by altering membrane potential

 Examples: ACh and amino acids

– Indirect action: neurotransmitter acts through intracellular second messengers,

usually G protein pathways

 Broader, longer-lasting effects similar to hormones

 Biogenic amines, neuropeptides, and dissolved gases

Classification of Neurotransmitters by

Chemical Structure (11

Actions: direct versus indirect (cont.)

– Neuromodulator: chemical messenger released by neuron that does not directly

cause EPSPs or IPSPs but instead affects the strength of synaptic transmission

 May influence synthesis, release, degradation, or reuptake of neurotransmitter

 May alter sensitivity of the postsynaptic membrane to neurotransmitter.

 May be released as a paracrine

– Effect is only local

Channel-linked receptors

– Ligand-gated ion channels

– Action is immediate and brief

– Excitatory receptors are channels for small cations

 Na+ influx contributes most to depolarization

– Inhibitory receptors allow Cl– influx that causes hyperpolarization

Neurotransmitter Receptors

G protein–linked receptors

– Responses are indirect, complex, slow, and often prolonged

– Involves transmembrane protein complexes

– Cause widespread metabolic changes

– Examples:

 Muscarinic ACh receptors

 Receptors that bind biogenic amines

 Receptors that bind neuropeptides

Mechanism:

 Neurotransmitter binds to G protein–linked receptor, activating G protein

 Activated G protein controls production of second messengers, such as cyclic

AMP, cyclic GMP, diacylglycerol, or Ca2+

 Second messengers can then:

– Open or close ion channels

– Activate kinase enzymes

– Phosphorylate channel proteins

– Activate genes and induce protein synthesis

Neural Integration

neurons functioning together in groups

• Groups contribute to broader neural functions

• There are billions of neurons in CNS

– Must have integration so that the individual parts fuse to make a smoothly

operating whole

Neuronal pool

functional groups of neurons

– Integrate incoming information received from receptors or other neuronal pools

– Forward processed information to other destinations

Simple neuronal pool

– Single presynaptic fiber branches and synapses with several neurons in pool

– Discharge zone: neurons closer to incoming fiber are more likely to generate

impulse

– Facilitated zone: neurons on periphery of pool are farther away from incoming

fiber; usually not excited to threshold unless stimulated by another source

Patterns of Neural Processing

Serial processing

– Input travels along one pathway to a specific destination

 One neuron stimulates next one, which stimulates next one, etc.

– System works in all-or-none manner to produce specific, anticipated response

– Best example of serial processing is a spinal reflex

Reflexes

 Rapid, automatic responses to stimuli

 Particular stimulus always causes same response

 Occur over pathways called reflex arcs that have five components:

– Receptor

– Sensory neuron

– CNS integration center

– Motor neuron

– Effector

Parallel processing

– Input travels along several pathways

– Different parts of circuitry deal simultaneously with the information

 One stimulus promotes numerous responses

– Important for higher-level mental functioning

– Example: A sensed smell may remind one of an odor and any associated

experiences

Types of Circuits

Circuits: patterns of synaptic connections in neuronal pools

• Four types of circuits

– Diverging

– Converging

– Reverberating

– Parallel after-discharge

Developmental Aspects of Neurons

Nervous system originates from neural tube and neural crest formed from ectoderm

• The neural tube becomes CNS

– Neuroepithelial cells of neural tube proliferate into number of cells needed for

development

– Neuroblasts become amitotic and migrate

– Neuroblasts sprout axons to connect with targets and become neurons

Growth cone: prickly structure at tip of axon that allows it to interact with its environment

via:

– Cell surface adhesion proteins (laminin, integrin, and nerve cell adhesion

molecules, or N-CAMs), which provide anchor points

– Neurotropins that attract or repel the growth cone

– Nerve growth factor (NGF), which keeps neuroblast alive

– Filopodia are growth cone processes that follow signals toward target

Once axon finds its target, it then must find right place to form synapse

– Astrocytes provide physical support and the cholesterol needed for construction of

synapses

• About two-thirds of neurons die before birth

– If axons do not form a synapse with their target, they are triggered to undergo

apoptosis (programmed cell death)

– Many other cells also undergo apoptosis during development

During childhood and adolescence learning reinforces certain synapses and prunes

away others

– Recent evidence suggests genes that promote excessive synaptic pruning may

predispose an individual to schizophrenia

• Neurons are amitotic after birth; however, there are a few special neuronal populations

that continue to divide

– Olfactory neurons and hippocampus