Chapter 11

Fundamentals of the Nervous System and Nervous Tissue

J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.

The Nervous System

The Nervous System is the rapid control system of the body

There are two anatomical divisions to the Nervous System: The Central Nervous System (CNS) The Peripheral Nervous System (PNS) They work together as a single coordinated

whole

The Functions of the Nervous System There are three

interconnected functions: sensory input

from millions of specialized receptors

receive stimuli

integration process stimuli interpret

stimuli

motor output cause response at many

effector organs

Organization of the Central Nervous System

the Brain and Spinal Cord

process & integrate information, store information, determine emotions

initiate commands for muscle contraction, glandular secretion and hormone release (regulate and maintain homeostasis)

connected to all other parts of the body by the Peripheral Nervous System (PNS)

Organization of the Peripheral NS anatomical connections

spinal nerves are connected to the spinal cord

cranial nerves are connected to the brain

two functional subdivisions sensory (afferent) division

somatic afferents - skin, skeletal muscle, tendons, joints

special sensory afferents visceral afferents - visceral

organs motor (efferent) division

motor (efferent) neurons muscles/glands

Organization of the PNS (continued) motor (efferent) division

has two parts: Somatic Nervous System

(SNS) voluntary motor neurons output to skeletal muscles

Autonomic Nervous System (ANS) involuntary visceral motor

neurons output to smooth muscle,

cardiac muscles and to glands

two cooperative components:• sympathetic division sympathetic division • parasympathetic divisionparasympathetic division

Autonomic Nervous System Sympathetic

Division – for muscular exertion and for “fight or flight” emergencies

Parasympathetic Division – for metabolic/ physiologic “business as usual” (“feed or breed”)

Nervous Tissue

Review the microanatomy of nervous tissue in Review the microanatomy of nervous tissue in lab and in the PPT with audio: CH11 Histology lab and in the PPT with audio: CH11 Histology of Nervous Tissueof Nervous Tissue

Nerve cell physiology is primarily a cell Nerve cell physiology is primarily a cell membrane phenomenonmembrane phenomenon

Information transmission differs between Information transmission differs between dendrites and axonsdendrites and axons

Neuron Processes - Dendrites

short, tapering, highly branched extensions of the soma

not myelinated contain some cell organelles receptive—initiate and transmit graded potentials (not

action potentials) to the cell body

Neuron Processes - Axons A single process that

transmits action potentials from the soma

Originates from a cone-shaped “axon hillock”

May be long (1 meter) or short (<1 mm) long axons called nerve fibers

Up to 10,000 terminal branches each with an axon terminal

that synapses (joins) with a neuron or an effector (muscle or gland cell)

Axons (continued) Axoplasm: the cytoplasm of the axon Axolemma: the cell membrane of the

axon, specialized to initiate and conduct action potentials (nerve impulses) initiated at the axon hillock (trigger zone),

travels to the axon terminal causes release of neurotransmitter from

terminal neurotransmitters can excite or inhibit transfers a control message to other

neurons or effector cells

Histology of Neurons – Myelin Sheath

lipid-rich, segmented covering on axons

most larger, longer axons are myelinated

dendrites are never myelinated myelin protects & electrically

insulates the axon increases the speed of nerve

impulses

myelinated fibers conduct impulses 10-150x faster than unmyelinated fibers

150 m/sec vs. 1 m/sec

Myelinating Cells neurolemmocytes (Schwann

cells) in the Peripheral NS

oligodendrocytes in the Central NS

Myelination occurs during fetal

development and the first year of life

each myelinating cell wraps around an axon up to 100 times, squeezing its cytoplasm and organelles to the periphery myelin sheath: multiple layers of

the cell membrane neurolemma (sheath of

Schwann): outer layer containing the bulk of the cytoplasm and cell organelles

Myelinated and Unmyelinated Axons Myelinated Fibers

Myelin sheath neurofibril nodes

(Nodes of Ranvier) periodic gaps in the myelin sheath between the neurolemmocytes

Unmyelinated Fibers surrounded by

neurolemmocytes but no myelin sheath present

neurolemmocytes may enclose up to 15 axons (unmyelinated fibers)

neurolemmocytes guide regrowth of neuron processes after injury

Myelination In the Central NS Gray matter - unmyelinated cell bodies & processes White matter – myelinated processes in various fiber

tracts

Classification of Neurons

Structural: based on the number of processes extending from the cell body

Functional: based on the direction (location) of nerve impulses

We will focus on functional classification

Afferent (= Sensory) Neurons afferent = towards CNS

nerve impulses from specific sensory receptors (touch, sight, etc.) are transmitted to the spinal cord or brain (CNS)

afferent neuron cell bodies are located outside the CNS in ganglia

Efferent (= Motor) Neurons efferent = away from

CNS

nerve impulses from CNS (brain and spinal cord) are transmitted to effectors (muscles, endocrine and exocrine glands)

efferent neuron cell bodies are located inside the CNS

Association Neurons (= Interneurons)

carry nerve impulses from one neuron to another

99% of the neurons in the body are interneurons

most interneurons are located in the CNS

Neurophysiology - Definitions voltage

the measure of potential energy generated by separated charges

always measured between two points – the inside versus the outside of the cell

referred to as a potential - since the charges (ions) are separated there is a potential for the charges (ions) to move along the charge gradient

Neurophysiology - Definitions current

the flow of electrical charge from one point to another

in the body, current is due to the movement of charged ions

resistance the prevention of the movement of charges

(ions) caused by the structures (membranes)

through which the charges (ions) have to flow

Neurophysiology - Basics Cell interior and exterior have different chemical

compositions Na+/K+ ATPase pumps change the ion concentrations a semi-permeable membrane allows for separation of

ions

Ions attempt to reach electrochemical equilibrium two forces power the movement of ions

individual ion concentrations (chemical gradients) net electrical charge (overall charge gradient)

the balance between concentration (chemical) gradients and the electrical gradient known as the electrochemical equilibrium

the external voltage required to balance the concentration gradient is the equilibrium (voltage) potential

Neurophysiology - Membrane Ion Channels regulate ion

movements across cell membrane

each is specific for a particular ion or ions

many different types may be passive (leaky) may be active (gated)

gate status is controlled gated channels are

regulated by signal chemicals or by other changes in the membrane potential (voltage potential)

Resting Membrane Potential (RMP) electrical charge gradient

associated with outer cell membrane

present in all living cells the cytoplasm within the

cell membrane is negatively charged due to the charge disequilibrium concentrations of cations and anions on either side of the membrane

RMP varies from about -40 to -90 millivolts (a net negative charge inside relative to a net positive charge outside the cell)

Resting Membrane Potential (cont.) RMP is similar to a battery

stores an electrical charge and can release the charge 2 main reasons for this:

ion concentrations on either side of the plasma membrane are due to the action of the Na+/K+ ATPase pumps primarily, Na+ and Cl- are outside; the membrane is polarized primarily, K+, Cl-, proteins- and organic phosphates- are inside

plasma membrane has limited permeability to Na+ and K+ ions

Resting Membrane Potential (cont.) Resting conditions

Na+/K+ ATPase pumps 3 Na+ ions out and 2 K+

ions in per ATP hydrolysis – opposing their concentration gradients concentration gradient drives Na+ to go into the cell concentration gradient drives K+ to go out of the cell

if the cell membrane were permeable to Na+

and K+ ions, then Na+ and K+ ions would diffuse along their electrical and chemical gradients and would reach equilibrium

if the cell was at equilibrium in terms of ion concentrations and charge, their would be no potential energy available for impulse transmission

Resting Membrane Potential (cont.) Neuron Membrane at rest is polarized

the cytoplasm inside is negatively charged relative to the outside

the net negative charge in the cytoplasm attracts all cations to the inside some Na+ leaks in, despite limited membrane

permeability Na+-K+ ATPase keeps working to pump 3 Na+

ions out and 2 K+ ions in, opposing the two concentration gradients (for Na+ and K+)

Resting Membrane Potential (cont.)

Here is the electrochemical gradient at rest: the resting potential

Membrane Potentials As Signals cells use changes in

membrane potential (voltage) to exchange information voltage changes occur by

two means:1. changing the membrane

permeability to an ion; or2. changing the ion

concentration on either side of the membrane

these changes are made by ion channels passive channels – leaky: K+ active channels:

• chemically gated – by neurotransmitters

• voltage gated

Types of Membrane Potentials graded potentials

graded = different levels of strength

dependent on strength of the stimulus

action potentials in response to

graded potentials of significant strength

signal over long distances

all or nothing

Types of Membrane Potentials

graded potentials and action potentials may be either: hyperpolarizing

increasing membrane polarity

making the inside more negative

depolarizing decreasing membrane

polarity making the inside less

negative = more positive

Properties of Action Potentials a nerve impulse (action potential) is

generated in response to a threshold graded potential

depolarization change in the membrane polarization stimuli reach a threshold limit and open

voltage-gated Na+ channels Na+ ions rush into the cell down the Na+

concentration and electrical gradients the cytoplasm inside the cell becomes positive reverses membrane potential to +30 mV

local anesthetics prevent opening of voltage-gated Na+ channels - prevent depolarization

Sequence of Events in Action Potentials

1. Resting membrane potential

Sequence of Events in Action Potentials

2. Depolarizationa) stimulus

strength reaches threshold limit

b) voltage gated Na+ channels open

c) Na+ flows into the cytoplasm

d) More V-gated Na+ channels open

[positive feedback]

Sequence of Events in Action Potentials3. Repolarization

a) voltage gated K+ channels open

b) voltage gated Na+ channels close

Sequence of Events in Action Potentials

4. Hyperpolarization

a)gated Na+ channels are reset to closed

b)membrane remains hyperpolarized until K+ channels close, causing the relative refractory period

Repeat the process:

Sequence of Events in Action Potentials

1. Resting membrane potential

Sequence of Events in Action Potentials

2. Depolarizationa) stimulus

strength reaches threshold limit

b) voltage gated Na+ channels open

c) Na+ flows into the cytoplasm

d) More V-gated Na+ channels open

[positive feedback]

Sequence of Events in Action Potentials3. Repolarization

a) voltage gated K+ channels open

b) voltage gated Na+ channels close

Sequence of Events in Action Potentials

4. Hyperpolarization

a)gated Na+ channels are reset to closed

b)membrane remains hyperpolarized until K+ channels close, causing the relative refractory period

The All-or-None Principle

stimuli/neurotransmitters arrive and open some of the chemically-gated Na+ channels

if stimuli reach the threshold level depolarization occurs voltage-gated Na+ channels open an Action Potential is generated which is constant

and at maximum strength

if stimuli do not reach the threshold level nothing happens

Repolarization Re-establishing the resting membrane

polarization state threshold depolarization opens Na+ channels

Na+ ions flow inward, making the cell interior more positive a few milliseconds later, K+ channels also open

K+ channels open more slowly and remain open longer K+ ions flow out along its concentration and charge

gradients carries positive (+) charges out, making the cell interior

more negative (-) Ion movements drive the membrane potential back

toward resting membrane potential value Na+/K+ ATPase continue pumping ions, adjusting

levels back to resting equilibrium levels hyperpolarization – briefly the exterior of the

membrane is more negative than resting potential voltage level

Refractory Periods Absolute Refractory

Period the time period during

which second AP cannot be initiated

due to closure of voltage-gated Na+ channels

the voltage-gated Na+ channels must be reset before the membrane can respond to the next stimulus

Many physiologists consider this to be the start of the absolute refractory period

Refractory Periods Relative Refractory

Period The time period during

which a second AP can be initiated with a suprathreshold stimulus

K+ channels are open, Na+ channels are closed

the membrane is still hyperpolarized

Propagation of an Action Potential the movement of an Action Potential down an

unmyelinated axon a local electrochemical current, a flow of charged

ions influx of sodium ions attraction of positive charges for negative area of

membrane nearby depolarizes nearby membrane – opening V-gated Na+

channels

Propagation of an Action Potential

destabilizing the adjacent membrane makes the Action Potential self-propagating and self-sustaining

the Action Potential renews itself at each region of the membrane – a relatively slow process because so much is happening at the molecular level

Conduction Velocity physical factors may influence impulse

conduction heat increases conduction velocity cold decreases conduction velocity

2 structural modifications can increase impulse velocity: increase neuron diameter - decreases

resistance insulate the neuron - myelin sheath

myelinated fibers may conduct as rapidly as 150 m/sec

unmyelinated may conduct as slowly as 0.5 m/sec

Saltatory Conduction

not a continuous region to region depolarization instead, a “jumping” depolarization myelinated axons transmit an Action Potential differently

the myelin sheath acts as an insulator preventing ion flows in and out of the membrane

neurofibral nodes (node of Ranvier) interrupt the myelin sheath and permit ion flows at the exposed locations on the axon membrane

the nodes contain a high density of voltage-gated Na+ channels

Saltatory Conduction in a myelinated fiber, the ionic current flows in at

each node and travels through the axoplasm to the next node

each node depolarizes in sequence, renewing the Action Potential at that node

the Action Potential jumps to next node very rapidly

energy efficient – the membrane only has to depolarize and repolarize at the nodes

less Na+/K+ ATPase activity is required, therefore, less energy is required

The Synapse Function

there must be a means of communication between each neuron and the next target cell

the synapse is the connection

Organization presynaptic neuron postsynaptic neuron separated by synaptic

cleft

The Two Types of Synapses (1) electrical synapses

gap junctions – found in cardiac muscle and in some smooth muscle tissues

direct, rapid electrochemical connections between neurons

may be bidirectional; useful for coordinated contraction rare in adults

(2) chemical synapses specialized for synthesis, release, reception and

removal of neurotransmitters neurotransmitters

chemical signal molecules released from a presynaptic neuron function to open or close chemically-gated ion channels effect membrane permeability and membrane potential

Action of a Chemical Synapse Presynaptic Events

an action potential reaches the axon terminal and depolarizes the terminal voltage gated Ca2+ channels open; Ca2+ ions enter the axoplasm neurotransmitter is released by exocytosis

neurotransmitter molecules diffuse across the cleft

Action of a Chemical Synapse (cont.) Postsynaptic Events

1) the neurotransmitters bind to specific postsynapticreceptors

2) gated ion channels open as a result 3) neurotransmitter molecules are eliminated quickly

a) degraded by extracellular enzymes in the synapse, with the products re-uptaken and recycled by the axon terminal

b) diffuse away from the synapse to the blood circulation

Postsynaptic Potentials EPSP

excitatory postsynaptic potential

provides a small local depolarization

generally results from opening Na+ channels

IPSP inhibitory postsynaptic

potential provides a small local

hyperpolarization generally results from

opening K+ or CL- channels

Summation of Postsynaptic Potentials temporal – rapid repeated stimulation from 2

or more presynaptic neurons spatial – simultaneous stimulation at 2 or

more different places on the neuron by presynaptic neurons

EPSPs and IPSPs counteract each other

End Chapter 11

The Nernst Equation

Ex= lnRT [X]out

zF [X]in

EX= Equilibrium potential of ion X in voltsR = gas constantT = temperature in kelvinsz = charge of each ionF = Faraday’s constant (96,500 coulombs/gram-equivalent charge[X] = ion concentration

At 38°C, (the standard temperature of many mammals) & converting ln:

Ex= log 61 [X]out

z [X]in

The Goldman-Hodgkin-Katz Equation

ENa,K,Cl= logRT PK[K+]out + PNa[Na+]out + PCl[Cl-]in

F PK[K+]in + PNa[Na+]in + PCl[Cl-]out

EX= Equilibrium potential of all ions in voltsR = gas constantT = temperature in kelvinsF = Faraday’s constant (96,500 coulombs/gram-equivalent charge

PERMEABILITY CHANGES DEPENDING UPON NEURON STATUS

At rest: PK:PNa:PCl=1/0.04/0.45

At Action Potential Peak: PK:PNa:PCl=1/20/0.45

The Goldman-Hodgkin-Katz Equation

ENa,K,Cl= logRT PK[K+]out + PNa[Na+]out + PCl[Cl-]in

F PK[K+]in + PNa[Na+]in + PCl[Cl-]out

At rest: PK:PNa:PCl=1/0.04/0.45

Ion Species Extracellular (mM)

Intracellular (mM)

K+ 5 150

Na+ 150 15

Cl- 120 10