Chapter 12
Nervous Tissue
•
INTRODUCTION
•
The nervous system, along with the endocrine system, helps to keep controlled conditions within limits that maintain health
and helps to maintain homeostasis.
•
The nervous system is responsible for all our behaviors, memories, and movements.
•
The branch of medical science that deals with the normal functioning and disorders of the nervous system is called
neurology.
•
Comparison of the Nervous and Endocrine Systems
•
The nervous and endocrine systems work together to maintain homeostasis, and they use some of the same chemicals to carry out
their tasks. The two systems differ in their means of communication and speed of response to stimulus.
•
Endocrine
Nervous
•
•
Mediator Molecules
Hormones
Action potentials and neurotransmitters
•
•
Time to Onset of Action
Seconds to hours or days
•
•
Typically within milliseconds
Target Cells
Virtually all body cells
•
Cardiac muscle, smooth muscle, Skeletal muscle,
glands and other Neurons.
•
•
Duration of Action
Generally longer
Generally briefer
Introduction to the Nervous System: General Functions
•
Nervous system activities
–
–
–
Collects information
•
specialized nervous structures, receptors
•
monitor changes in external and internal environment, stimuli
•
transmits information to the central nervous system via sensory (afferent) neurons
Processes and evaluates information (integration)
•
integrates information (usually involves association (interneurons) neurons.
•
then determines if response required
Initiates response to information
1
•
responses are carried via motor (efferent) neurons
•
initiate response via nerves to effectors
•
include muscle tissue and glands
•
e.g., muscle contraction or change in gland secretion
Structural organization: central versus peripheral nervous system
–
–
•
•
Central nervous system
•
includes brain and spinal cord
•
brain protected in the skull
•
spinal cord protected in the vertebral canal
Peripheral nervous system
•
includes nerves, bundles of neuron processes
•
includes ganglia, clusters of neuron cell bodies
Functional organization: sensory versus motor nervous system
–
–
–
Sensory nervous system
•
also known as afferent nervous system
•
responsible for receiving sensory information from receptors
•
transmits information to the CNS
•
further divided into somatic and visceral sensory
Somatic sensory
•
detects stimuli that we consciously perceive
•
receptors include:
•
eyes and nose
•
tongue and ears
•
skin
•
proprioceptors (receptors detecting body position)
Visceral (Autonomic) sensory
•
detects stimuli we do not consciously perceive
•
receptors include:
•
•
structures within blood vessels
•
structures within internal organs
e.g., detecting stretch of organ wall
2
–
•
Motor nervous system
•
also known as efferent nervous system
•
initiates and transmits motor output from CNS
•
transmits information to the effectors
•
may be further divided into the somatic and visceral parts
Functional organization: sensory versus motor nervous system
–
Somatic motor
•
transmits motor output from CNS to voluntary skeletal muscles
•
effector consciously controlled
•
–
•
e.g., pressing on accelerator of your car
Autonomic motor
•
transmits output from CNS without conscious control
•
transmits to cardiac muscle, smooth muscle, glands
•
Subdivisions include:
•
Sympathetic division – “Fight or Flight”
•
Parasympathetic division – “SLUDD”
•
Enteric division – GI tract
Enteric Division
The nervous system exerts a profound influence on all digestive processes, namely motility, ion transport associated with secretion and absorption,
and gastrointestinal blood flow. Some of this control emanates from connections between the digestive system and central nervous system, but
just as importantly, the digestive system is endowed with its own, local nervous system referred to as the enteric or intrinsic nervous system.
The magnitude and complexity of the enteric nervous system is immense - it contains as many neurons as the spinal cord.
The enteric nervous system, along with the sympathetic and parasympathetic nervous systems, constitute the autonomic nervous system.
Nervous Tissue: Neurons
•
Two cell types in nervous tissue
–
–
Neurons
•
basic structural unit of the nervous system
•
excitable cells that transmit electrical signals
Glial cells (Neuroglia)
•
nonexcitable cells that primarily support and protect neurons
Nervous Tissue—Neurons: General Characteristics
•
Characteristics of neurons
3
–
Excitability
•
–
Conductivity
•
–
–
electrical charges propagated along membrane
Secretion
•
–
responsive to stimulation
release neurotransmitters in response to electrical charges
Amitotic
•
Mitotic activity lost in most neurons
•
Some exceptions (e.g., hippocampus)
Extreme longevity
most formed before birth still present in advanced age
•
Components of neurons
–
Cell body
•
enclosed by plasma membrane
•
contains cytoplasm surrounding a nucleus
•
neuron’s control center
•
conducts electrical signals to axon
•
perikaryon, cytoplasm within cell body
•
nucleus with prominent nucleolus
•
free and bound ribosomes termed chromatophilic substance (Nissl bodies) due to dark staining with basic dyes
•
gray color of gray matter
–
–
–
due to chromatophilic substance and lack of myelin
Dendrites
•
short processes branching off cell body
•
may have one or many
•
receive input and transfer it to cell body
•
more dendrites = more input possible
Axon
•
longer process emanating from cell body
•
makes contact with other neurons, muscle cells, or glands
•
first part, a triangular region, axon hillock
4
•
cytoplasm here termed axoplasm
•
plasma membrane here termed axolemma
•
devoid of chromatophilic substance
•
gives rise to side branches, axon collaterals
•
branch extensively at distal end into telodendria (axon terminals)
•
at extreme tips, expanded regions, synaptic knobs
•
knobs containing numerous synaptic vesicles
–
•
contain neurotransmitter
Cytoskeleton
–
Composed of microfilaments, intermediate filaments, microtubules
–
Intermediate filaments, termed neurofilaments
•
aggregate to form bundles, neurofibrils
•
provide tensile strength through the neuron
Nervous Tissue—Neurons: Neuron Transport
•
Bidirectional axonal transport
–
–
Axons dependent on cell body
•
for newly synthesized materials
•
for break down of used materials
Anterograde transport
•
–
Retrograde transport
•
•
•
movement of materials from cell body to synaptic knobs
movement of materials from synaptic knobs to cell body
Fast axonal transport
–
Occurs at about 400 mm per day
–
Involves molecular motors (dynein and kinesin)
–
Involves movement along microtubules
–
Power from specialized motor proteins that split ATP
–
Anterograde or retrograde motion possible
•
anterograde transport of vesicles, organelles, glycoproteins
•
retrograde transport of used vesicles, potentially harmful agents
Slow axonal transport
5
–
Occurs at about 0.1 to 3 mm per day
–
Results from flow of axoplasm
–
Substances only moved from cell body towards knob
•
enzymes, cytoskeletal components, new axoplasm
Nervous Tissue—Neurons: Classification of Neurons
•
Structural classification
–
Structural classification of neurons
•
–
–
–
–
•
according to number of neuron processes
Multipolar neurons
•
most common type
•
have at least three processes coming off the neuron cell body
•
have many dendrites and a single axon
•
motor and association neurons
Bipolar neurons
•
have two processes extending from cell body
•
one dendrite and one axon
•
limited, e.g., special senses
Unipolar neurons
•
have single short neuron process
•
emerges from cell and branches like a T
•
also called pseudounipolar
•
start out as bipolar neurons during development
•
axons with peripheral process (dendrites to cell body)
•
axons with central process (cell body into CNS)
•
somatic sensory neurons
Anaxonic neurons
•
have dendrites and no axons
•
produce local electrical changes but no action potentials
•
Dendrodendritic transmission
•
Components of complex interneuronal circuits such as those involved in learning and memory
Functional classification
6
–
–
Sensory neurons (afferent neurons)
•
neurons of the sensory nervous system
•
conduct input from somatic and visceral receptors
•
most unipolar, few bipolar
•
cell bodies usually in posterior root ganglia, outside CNS
Motor neurons (efferent neurons)
•
neurons of the motor nervous system
•
conduct motor output to somatic and visceral effectors
•
all multipolar
•
most cell bodies in CNS
–
Interneurons (association neurons)
–
entirely within the CNS
–
receive stimulation from many other neurons
–
receive, process, and store information
–
“decide” how body responds to stimuli
–
facilitate communication between sensory and motor neurons
–
99% of neurons
–
generally multipolar
Nervous Tissue—Neurons: Relationship of Neurons and Nerves
•
Nerve
–
Cablelike bundle of parallel axons surrounded by connective tissue
–
Macroscopic structure
–
Epineurium
–
–
•
thick layer of dense irregular connective tissue
•
encloses the entire nerve
•
provides support and protection
Perineurium
•
layer of dense irregular connective tissue
•
wraps bundles of axons, fascicles
•
supports blood vessels
Endoneurium
7
•
delicate layer of areolar connective tissue
•
separates and electrically insulates each axon
•
has capillaries that supply the axon
Nervous Tissue—Neurons: Relationship of Neurons and Nerves
Classification of nerves
•
Structural classification
–
Cranial nerves (12 pairs)
•
–
Spinal nerves (31 pairs)
•
•
extend from brain
extend from spinal cord
Functional classification
–
Sensory nerves
•
–
Motor nerves
•
–
contain only sensory neurons
contain primarily motor neurons
Mixed nerves
•
contain both sensory and motor neurons
•
most named nerves in this category
•
individual neurons transmitting one type of information
Synapses
•
•
Synapse
–
Where neuron functionally connected to neuron or effector
–
Two types: chemical and electrical
Chemical synapse
–
Most common
–
Composed of presynaptic neuron, signal producer
–
Composed of postsynaptic cell, signal receiver
–
Between axon and any portion of postsynaptic neuron
•
–
most commonly with a dendrite
Knob almost touches the postsynaptic neuron
•
narrow fluid filled gap, the synaptic cleft
8
•
Terminology
•
Ganglion (ganglia) are groups of neuron cell bodies lying outside the central nervous system (CNS).
•
Nucleus (nuclei) are clusters of cells bodies and unmyelinated neuron processes within the central nervous system (CNS).
•
Nerves are cordlike bundles of hundreds to thousands of axons plus connective tissue that lie outside the CNS.
•
Tracts are bundles of hundreds to thousands of axons found in the CNS.
Nervous Tissue—Glial Cells: General Characteristics
•
Glial cells (neuroglia)
–
Nonexcitable cells found in CNS and PNS
–
Smaller than neurons
–
Capable of mitosis
–
Far outnumber neurons (50 to 1)
–
Half volume of nervous system
–
Physically protect and nourish neurons
–
Provide physical scaffolding for nervous tissue
•
–
help guide migrating neurons to their destination
Critical for normal function at neural synapses
Glial cells of the CNS
•
Astrocytes
–
Starlike shape from surface projections
–
Processes touching capillary walls and neurons
•
–
•
ends termed perivascular feet
Most abundant glial cell in CNS
Astrocytes
–
–
Help form the blood-brain barrier
•
feet wrap around capillaries in the brain
•
together form the blood-brain barrier
•
strictly controls substances entering brain nervous tissue from blood
•
protects neurons from toxins
•
allows nutrients to pass
Regulate tissue fluid composition
•
control movement of substances between blood and interstitial fluid
9
e.g., regulate K+ concentration
•
need constant K+ level for neuron electrical activity
–
Reabsorbs neurotransmitters
–
Form a structural network
•
–
–
•
•
cytoskeleton strengthening and organizing nervous tissue
Assist neuronal development
•
direct development of neurons in fetal brain
•
secrete chemicals regulating formation of connections
Occupy the space of dying neurons
•
space formerly occupied by dead neurons
•
filled by cells produced by astrocyte division
Ependymal cells
–
Line internal cavities of brain and spinal cord
–
Ciliated simple cuboidal or simple columnar epithelial cells
–
Slender processes with extensive branching
–
Form choroid plexus (blood – cerebrospinal fluid barrier) with nearby blood capillaries
•
helps produce cerebrospinal fluid
•
•
•
•
liquid that bathes external CNS and fills internal cavities
cilia helping to circulate CSF
Microglia
–
Small cells with slender branches
–
Smallest percentage of CNS glial cells
–
Phagocytic cells of the immune system
–
Wander CNS and replicate in infection
–
Engulf infectious agents
–
Remove debris from dead or damaged tissue
Oligodendrocytes
–
Large cells with slender extensions
–
Processes ensheathing portions of axons of different neurons
–
Processes repeatedly wrapping around axon
–
Insulate axons of the CNS in a myelin sheath
10
•
–
Prevent passage of ions through axonal membrane
–
Allow for faster action potential propagation through CNS
Satellite cells
–
Arranged around neuronal cell bodies in a ganglion
–
Physically separate cell bodies in ganglion from surrounding fluid
–
Regulate the exchange of nutrients and waste products
•
e.g., surrounding bodies of sensory neurons in a posterior root ganglion
Glial cells of the PNS
•
Neurolemmocytes
–
Also known as Schwann cells
–
Ensheathe PNS axons to form myelin sheath
–
Allows for faster action potential propagation
Clinical View: Tumors of the Central Nervous System
–
Neoplasm from unregulated cell growth, tumors
–
Sometimes occur in CNS
–
Tumors originating from the brain, primary brain tumors
–
Typically originate in supporting tissues
–
•
tissues with capacity to undergo mitosis
•
from meninges (protective membranes of CNS) or glial cells
Gliomas, glial cell tumors
•
may be relatively benign
•
may be malignant, capable of metastasizing
Nervous Tissue—Glial Cells: Myelination
•
Myelination
–
Process by which part of an axon wrapped in myelin
–
Myelin, insulating covering around axon
•
consists of repeating layers of glial cell plasma membrane
•
has high proportion of lipids
•
gives glossy appearance and insulates axon
–
Completed by neurolemmocytes (PNS)
–
Completed by oligodendrocytes (CNS)
11
•
Process of myelination
–
Neurolemmocyte starts to wrap around axon
–
Its cytoplasm and plasma membrane begin to form layers
–
Wrapping continues
–
Layers of plasma membrane form the myelin sheath
–
Its cytoplasm and nucleus is pushed to the periphery
•
•
Neurolemmocyte in the PNS
–
Can myelinate only 1 mm of single axon
–
Takes many to myelinate entire axon
–
Gaps between neurolemmocytes
•
•
•
termed neurilemma
neurofibril nodes, or nodes of Ranvier
Oligodendrocyte in the CNS
–
Can myelinate 1 mm of many axons
–
Extensions wrapping around axons
–
No neurilemma formed
–
Neurofibril nodes between adjacent “wraps”
Unmyelinated axons
–
Associated with neurolemmocytes
–
No myelin sheath covers them
–
Axon in depressed portion of neurolemmocyte
–
Not wrapped in repeated layers
–
In CNS,
•
unmyelinated axons not associated with oligodendrocytes
Clinical View: Nervous System Disorders
Affecting Myelin
–
Multiple Sclerosis
•
progressive demyelination of neurons in CNS
•
autoimmune disorder
•
oligodendrocytes attacked by immune cells
•
repeated inflammatory events causing scarring and permanent loss of function
12
•
vision problems, muscle weakness and spasms, urinary and bladder problems, mood problems
–
An autoimmune disease that mainly affects young adults
–
Symptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinence
–
Myelin sheaths in the CNS become nonfunctional scleroses
–
Shunting and short-circuiting of nerve impulses occurs
–
Impulse conduction slows and eventually ceases
–
Some immune system–modifying drugs, including interferons and Copazone:
–
Hold symptoms at bay
–
Reduce complications
–
Reduce disability
Axon Regeneration
•
Factors influencing axon regeneration
–
PNS axons
•
–
–
•
vulnerable to cuts, trauma
Regeneration possible if
•
cell body intact
•
enough neurilemma remains
Regeneration success more likely if
•
amount of damage less extensive
•
smaller distance between site of damage and structure it innervates
Steps of axon regeneration
(1] Axon severed by trauma
[2] Sealing off and swelling of proximal portion of severed axon
•
disintegration of distal axon and myelin sheath
–
•
termed Wallerian degeneration
survival of neurilemma
[3]Formation of regeneration tube
•
neurilemma and remaining endoneurium
[4] Axon regeneration and remyelination
•
guided by regeneration tube
•
nerve growth factor released by neurolemmocytes
13
[5] Innervation restored
•
CNS axon regeneration
–
Extremely limited
•
growth-inhibiting molecules secreted by oligodendrocytes
•
larger number of axons crowded within the CNS
•
regrowth obstructed by scars from astrocytes and connective tissue
ELECTRICAL SIGNALS IN NEURONS
•
•
Excitable cells communicate with each other by action potentials or graded potentials.
•
Action potentials allow communication over short and long distances whereas graded potentials allow communication over
short distances only.
•
Production of both types of potentials depend upon the existence of a resting membrane potential and th presence of
certain types of ion channels.
•
The membrane potential is an electrical voltage across the membrane.
•
Graded and action potentials occur because of ion channels in the membrane that allow ion
the membrane that can change the membrane potential.
movement across
Electrophysiology of Neurons
•
Terminology
•
Membrane Potential. An electrical voltage difference across the plasma membrane.
•
Resting Membrane Potential. The membrane potential in excitable cells.
•
Current. The flow of electrical charge. In cells, the flow of ions (rather that electrons) constitutes the
•
Resistance. Inhibition of current.
•
Polarized. A cell which exhibits a membrane potential.
electrical current.
Ion Pumps and Gates
•
•
The two basic types of ion channels are leakage (nongated) and gated.
•
Leakage (nongated) channels are always open.
•
Gated channels open and close in response to some sort of stimulus.
•
Gated ion channels respond to voltage changes, ligands (chemicals), and mechanical pressure.
•
Voltage-gated channels respond to a direct change in the membrane potential.
•
Ligand-gated channels respond to a specific chemical stimulus.
•
Mechanically gated ion channels respond to mechanical vibration or pressure.
Pumps
•
Type of transport protein
14
•
Move substances against concentration gradient
•
Require energy
•
•
•
Channels
•
Move substances down concentration gradient
•
Leak (Leakage) channels
•
always open for continuous diffusion
•
e.g., sodium ion and potassium ion channels
Channels
•
Mechanically gated channels (stretch receptor)
•
•
normally closed
•
respond to membrane tension
•
Physical torsion or deformation opens the channel pore
Chemically (ligand) gated channels
•
•
e.g., sodium-potassium and calcium pumps in plasma membrane
•
normally closed
•
allow specific type of ion to diffuse when open
•
e.g., chemically gated K+ channels
Voltage-gated channels
•
normally closed
•
open in response to changes in electrical charge across membrane
•
allow specific type of ion to diffuse
•
e.g., voltage gated Na+ channels
Pumps
– Type of transport protein
– Move substances against concentration gradient
– Require energy
•
•
e.g., sodium-potassium and calcium pumps in plasma membrane
Channels
– Move substances down concentration gradient
– Leak (Leakage) channels
•
always open for continuous diffusion
15
•
•
e.g., sodium ion and potassium ion channels
Channels
– Mechanically gated channels (stretch receptor)
•
normally closed
•
respond to membrane tension
•
Physical torsion or deformation opens the channel pore
– Chemically (ligand) gated channels
•
normally closed
•
allow specific type of ion to diffuse when open
•
e.g., chemically gated K+ channels
– Voltage-gated channels
•
normally closed
•
open in response to changes in electrical charge across membrane
•
allow specific type of ion to diffuse
•
e.g., voltage gated Na+ channels
Ultrastructure of Neurons: Pumps and Channels
Distribution of pumps and channels
•
Entire plasma membrane of neuron
– Na+ leakage channels
– K+ leakage channels
•
present in greater numbers than Na+ leak channels
•
easier for K+ to move through
– Na+/K+ pumps
– important in maintaining resting membrane potential
•
Membrane of functional segments in a neuron
– Receptive segment
•
includes dendrites and cell body
•
chemically gated (ligand) channels and mechanically gated channels here (cation channels, K+, Cl-)
•
no significant voltage-gated channels
– Initial segment
•
composed of axon hillock
16
•
contains voltage-gated Na+ and K+ channels
– Conductive segment
•
length of the axon and its branches
•
contains voltage-gated Na+ and K+ channels
– Transmissive segment
•
includes synaptic knobs
•
contains voltage-gated Ca2+ channels and pumps
Ultrastructure of Neurons: Distribution of Substances and Membrane Potentials
•
Distribution of substances inside and outside neuron
– Essential for neuron function
– More prevalent within cytosol
•
negatively charged phosphate ions (e.g., in ATP)
•
negatively charged proteins
•
K+
– More prevalent in interstitial fluid
•
Na+
•
Cl-
17
•
Movement of substances and membrane potentials
–
Ions able to pass through membrane by transport proteins
–
Phosphate-containing molecules and proteins
•
–
Net movement dependent on electrochemical gradient
•
–
generally restricted from crossing
combination of the electrical and chemical gradient
Electrical gradient
•
difference in electrical charge between two areas
•
cells with differences in total positive and negative charges across membrane
•
exhibit electrical gradient at the membrane
•
inside relatively negative
•
outside relative positive
•
difference in charge termed a membrane potential
can be altered to create electrical currents
–
Chemical concentration gradient
•
unequal distribution between two areas
•
each substance with own chemical concentration gradient
•
e.g., K+ with a higher concentration inside the neuron
e.g., Na+ with a higher concentration outside the neuron
18

In a resting membrane potential the membrane potential is said to be polarized. This is due to an unequal distribution of ions across the
plasma membrane and the relative permeability of the plasma membrane to Na+ and K+. The four factors most responsible for
generating the resting membrane potential are:
K+ movement from the ICF to the ECF.
Anions (proteins and phosphates) in the ICF.
Na+ movement from the ECF to the ICF.
The Na+/K+ pump.
The resting membrane potential is around –70 millivolts for neurons.
Introduction to Neuron Physiology: Neurons
•
Concepts for electrical current in neurons
–
Neuron activity dependent upon electrical current
–
Voltage
–
•
measure of the amount of difference in electrical charge
•
measured in volts or millivolts
•
indicator of relative potential energy
Current
•
movement of charged particles
•
greater movement, greater current
•
can be harnessed to do work
19
•
Concepts for electrical current in neurons
–
Resistance
•
opposition to movement of charged particles
Graded Potentials
•
A graded potential is a small deviation from the resting membrane potential that makes the membrane either more polarized
(hyperpolarization) or less polarized (depolarization).
•
Graded potentials occur most often in the dendrites and cell body of a neuron.
•
The signals are graded, meaning they vary in amplitude (size), depending on the strength of the stimulus and localized.
20
21
Introduction to Neuron Physiology: Changing the Membrane Potential
•
Depolarization and hyperpolarization
–
Opening of chemically gated channels or voltage-gated channels
–
Causes change in ion flow across membrane
–
Alters resting membrane potential
–
Depolarization
–
•
•
inside of cell becomes more positive than RMP
•
e.g., from -70 mV to -60 mV
•
occurs when gated channels open
•
movement of Na+ into neuron
•
causes inside of neuron to become more positive
Hyperpolarization
•
inside of cell becomes more negative
•
e.g., from -70 mV to -80 mV
•
may result from opening of gated K+ channels
•
may result from opening of gated Cl- channels
•
loss of positive ion (K+) or gain of negatively charged ion (Cl-)
Graded potentials
–
Local potentials
22
–
Occur in the receptive segment of a neuron (dendrites and cell body)
–
Due to opening of chemically gated channels
–
Temporarily allow passage of small amount of specific ion
–
Local current established
–
•
ions moving parallel to plasma membrane
•
experiences resistance from contents of cytosol
•
eventually becomes weaker and ceases
May result in depolarization or hyperpolarization
•
–
depends on channel that opens
Degree dependent on stimulus magnitude
•
larger stimulus opening more chemically gated channels
•
flow of more ions
–
Decreases in intensity with distance along the membrane
–
Short-lived
•
lasts until local ion current ceases
•
Actions potentials are a sequence of rapid changes in membrane potential involving a depolarization followed by a
repolarization.
•
An action potential can be generated only in places where the plasma membrane has an adequate density of voltagegated channels.
•
Action potentials occur if local (graded) potentials rise to a critical level called threshold.
•
At threshold the Na+ voltage-gated channels open rapidly and the K+ voltage-gated channels open slowly. The
inside of the cell becomes more positive. This results in a reversal of polarity as Na+ move into the ICF. The cells is
said to be depolarized.
Actions Potentials
•
•
The Na+ gates close and the K+ gates are fully open resulting in K+ movement from the ICF to the ECF. The inside of the cells
becomes more negative. The cells is said to be repolarized.
•
The sodium/potassium pump returns the Na+ ions and K+ ions to their normal locations.
•
Action potentials are propagated, all-or-none, and have a refractory period.
Action potentials
•
Generated within the initial segment
•
Propagated along axon
•
Due to opening of voltage-gated channels
•
Threshold value
23
•
•
•
minimum voltage change to open voltage-gated channel
•
any value below this, a subthreshold value
If threshold value reached
•
channels open and membrane potential reversed
•
if Na+ channel opens, enters the neuron
•
makes inside relatively positive
•
flow of local current to adjacent areas
If threshold value reached
•
opening of voltage-gated channels in these areas
•
successive opening down the axon
•
followed by sequential opening of voltage-gated K+ channels
movement of K+ out of neuron returns membrane to RMP
–
–
involve temporary reversal of polarity across plasma membrane
•
inside becomes relatively positive
•
followed by a return to RMP
are self-propagated
•
–
maintain intensity as move to synaptic knob
obey the “all or none law”
•
if threshold reached, action potential sent
•
if not reached, no action potential sent
24
25
\
26
Anatomy of a Synapse
•
Synaptic knob
–
The expanded tip of the axon
–
Axon enlarged and flattened in this region
–
Houses synaptic vesicles, small membrane sacs
•
–
Has Ca2+ pumps embedded in plasma membrane
•
Has voltage-gated Ca2+ channels in membrane
–
Ca2+ flowing down concentration gradient if opened
–
Vesicles normally repelled from membrane of synaptic knob
–
Nerve signal propagated down motor axon
–
Triggers opening of voltage-gated Ca2+ channels
–
Movement of calcium down concentration gradient
–
Binding of calcium with proteins on synaptic vesicles
Merging of synaptic vesicles with synaptic knob membrane
•
•
from interstitial fluid into synaptic knob
Release of neurotransmitter from synaptic knob
–
•
because both normally negatively charged
Calcium entry at synaptic knob
•
•
establish calcium gradient, with more outside the neuron
–
•
•
filled with neurotransmitter
triggered by binding of Ca2+
–
Exocytosis of neurotransmitter into synaptic cleft
–
About 300 vesicles per nerve signal
Binding of neurotransmitter to ligand gates
–
Diffusion of ACh across synaptic cleft
–
Binds with ACh receptors within motor end plate
–
Causes excitation of muscle fiber
Transmission at chemical synapse
–
Neurotransmitter molecules released from synaptic knob
–
Released from synaptic vesicles into cleft
–
Diffusion of neurotransmitter across cleft
27
–
Binding of some neurotransmitters to receptors
–
Synaptic delay
•
–
time between neurotransmitter release and binding
Single postsynaptic neuron
•
often stimulated by more than one neuron
Neurotransmitter is removed from the synaptic cleft in three ways:
•
•
diffusion,
•
enzymatic degradation,
•
and uptake into cells (neurons and glia).
Electrical synapse
•
Much less common
•
Presynaptic and postsynaptic neuron physically bound together
•
Gap junctions present
•
No delay in passing electrical signal
•
In limited regions of brain and eyes
•
Electrical Synapses. In electrical synapses, action potentials conduct directly between adjacent cells through gap junctions. This type of
synapse is found in smooth muscle, cardiac muscle and some neurons. Two characteristics of electrical synapses are:
•
Faster communication. Action potentials conduct directly through gap junctions without the delay seen in chemical synapses.
•
Synchronization. Electrical synapses can synchronize groups of cells such as muscle fibers to act as a group.
Physiologic Events in the Neuron Segments: Receptive Segment
•
Postsynaptic potentials
–
Graded potentials that occur in postsynaptic neurons
–
Occur after release of neurotransmitter from presynaptic neuron
–
Opening of gated channels after binding of neurotransmitters
–
Results in small local potential
–
Postsynaptic neuron
–
•
able to bind many neurotransmitters at once
•
numerous postsynaptic potentials generated at once
Type of graded potential formed depends on neurotransmitter
•
excitatory or inhibitory neurotransmitter
28
Generation of EPSPs
•
Sequence of events
1)
2)
3)
Excitatory neurotransmitter crosses synaptic cleft.
•
binds to receptor
•
opens a chemically gated cation channel
More Na+ moves into neuron than K+ moves out.
Inside becomes slightly more positive.
•
5)
Local current of Na+ becomes weaker
•
6)
decreases in intensity with distance traveled
Degree of change in RMP
•
7)
less negative state called excitatory postsynaptic potential (EPSP)
dependent on amount of neurotransmitter bound per unit time
More excitatory neurotransmitter released
•
more cation channels open
•
greater change in the positive direction
•
e.g., from -70 mV to -65 mV
Generation of IPSPs
•
Sequence of events
1)
2)
Inhibitory neurotransmitter crosses synaptic cleft.
•
binds to chemically gated K+ channel or Cl- channel
•
depends on neurotransmitter and channels present
If neurotransmitter binds K+ channel, K+ moves out of neuron.
If neurotransmitter binds Cl-channel, Cl- flows into neuron.
3)
Inside of the cell becomes slightly more negative
•
4)
Local current of ions becomes weaker.
•
•
more negative state termed inhibitory postsynaptic potential (IPSP)
decreases in intensity with distance traveled toward initial segment
Simultaneous release
•
Excitatory and inhibitory neurotransmitters
•
•
may be simultaneously released from different neurons
Varied frequency of releasing neurotransmitter
29
•
Result: many EPSPs, many IPSPs, or both
Physiologic Events in the Neuron Segments: Initial Segment
•
Summation
–
Addition of graded postsynaptic potentials (IPSPs and EPSPs)
–
Occurs at the initial segment
–
Determines if threshold membrane potential is reached
•
–
If threshold reached
•
voltage-gated channels open
•
action potential generated that travels along axon
–
IPSPs negate effects of EPSPs
–
Thousands of EPSPs required to reach threshold
•
–
must arrive at nearly the same time
Spatial summation
•
release of neurotransmitter from multiple presynaptic neurons
•
action potential initiated if enough EPSPs generated
–
IPSPs negate effects of EPSPs
–
Thousands of EPSPs required to reach threshold
•
–
•
-55 mV, +15 mV from RMP
must arrive at nearly the same time
Spatial summation
•
release of neurotransmitter from multiple presynaptic neurons
•
action potential initiated if enough EPSPs generated
All or none law
–
If threshold reached, action potential propagated
–
If threshold not reached, not propagated
–
Same intensity of response to values greater than threshold
–
Similar to what occurs with a gun
•
with sufficient pressure on trigger, gun fired
•
with insufficient pressure on trigger, not fired
•
travels at same velocity even if pressure is greater than needed
•
30
Physiologic Events in the Neuron Segments: Conductive Segment
•
Nerve signal
–
The propagation of an action potential
–
Involves depolarization and repolarization
–
Threshold reached in initial segment
–
Initiates action potential along the axon (conductive segment)
Depolarization and its propagation
•
Positive change in membrane potential
–
Occurs only at plasma membrane
•
–
Channels triggered to open when threshold reached
–
Rapid entry of Na+
–
Inside of axon made positive
–
Channels open briefly before closing
•
•
change from activation state to temporary inactivation state
Propagation of depolarization
–
Sequential opening of voltage-gated Na+ channels along the axon
–
Flow of Na+ into cell
–
•
via voltage-gated Na+ channels
•
causes adjacent regions to also reach threshold
•
triggers voltage-gated Na+ channels in these areas
Process repeated rapidly down synaptic knob
•
does not go backwards
•
voltage-gated Na+ channels here in inactivated state
Local anesthetics
–
E.g., lidocaine
–
Inhibit action of voltage-gated Na+ channels
–
Block nerve signal
–
Pain signal blocked from reaching CNS
–
Application of ice
•
reduces pain sensation
•
slows transmission of sensory action potentials
31
Repolarization and its propagation
•
•
•
Return to resting membrane potential
–
Voltage-gated K+ channels normally closed
–
Stimulated to open by threshold
–
Not open until depolarization has ended
–
Exit of K+, making inside of axon negative
–
Return to RMP (-70 mV)
–
Triggers voltage-gated Na+ channels to return to resting state
Propagation of repolarization
–
Opening of voltage-gated K+ channels adjacent
–
Open sequentially along length of axon
Hyperpolarization and return to resting membrane potential
–
Voltage-gated K+ channels
•
–
Inside of neuron briefly more negative than RMP
•
–
open longer than time needed to reestablish RMP
hyperpolarized
Closure of K+ channels
RMP reestablished by Na+/K+ pumps
•
Refractory period
–
Brief time period after action potential initiated
–
During absolute refractory period
–
•
no amount of stimulus able to generate a second action potential
•
Na+ channels opened then closed in inactivated state
•
remain closed until potential almost to resting potential
•
ensures that action potential moves in one direction only
During relative refractory period
•
with greater stimulation, action potential possible
•
Na+ returned to resting state
•
neuron hyperpolarized
•
due to extended time K+ channels remain open
•
32
Physiologic Events in the Neuron Segments: Transmissive Segment
•
Activity at the synaptic knob
–
Calcium concentration gradient established by pumps
•
–
more calcium outside synaptic knob than in
Voltage-gated Ca2+ channels
•
triggered by propagated action potential
•
movement of calcium ions into synaptic knob
–
Binding of calcium to proteins of synaptic vesicles
–
Triggers fusion of synaptic vesicles with neuron plasma membrane
–
Neurotransmitters released into synaptic cleft by exocytosis
•
facilitated by numerous proteins
•
diffuse across cleft
•
bind to specific receptors on cell to be stimulated
Velocity of a Nerve Signal
•
Factors influencing velocity of nerve signal
–
Diameter of axon
•
–
•
larger diameter, faster the velocity of the signal
Myelination of axon
•
more important factor
•
faster velocity in myelinated axons
Continuous conduction
–
Occurs in unmyelinated axons
–
Sequential opening of voltage-gated Na+ and K+ channels
The step-by-step depolarization and repolarization along the plasma membrane of an axon is called continuous conduction.
This occurs along unmyelinated axons.
Velocity of a Nerve Signal: Propagation
•
Saltatory conduction
–
Occurs in myelinated axons
–
Action potentials propagated only at neurofibril nodes
–
Myelinated regions
•
with limited numbers of voltage gated Na+ and K+ channels
33
•
–
well insulated, preventing ion movement
Neurofibril nodes
•
with large number of voltage-gated Na+ and K+ channels
•
lack myelin insulation
•
In myelinated axons an action potential can occur only at the nodes of Ranvier. This generates ionic currents that quickly pass to the next
node of Ranvier stimulatng another action potential.
•
Saltatory conduction is faster and more energy-efficient than continuous condution.
•
Nerve signal in myelinated axon
–
–
–
–
Neurofibril node
•
initiation of action potential
•
diffusion of Na+ into axon
Myelinated regions
•
diffusion through axoplasm of axon
•
relatively fast
•
becomes weaker with distance as experiences resistance
Next neurofibril node
•
arrival of weak Na+ current
•
sufficient to cause opening of voltage-gated Na+ channels
•
new action potential initiated
Repetition of process
•
–
Increased speed in myelinated axons
•
–
action potential generated only at neurofibril nodes
More efficient
•
•
continuation of nerve signal to synaptic knob
less energy required for Na+/K+ pump to maintain RMP
Velocity of a Nerve Signal: Nerve Fiber Classification
•
Type A fibers. Large diameters, myelinated. Impulse conduction from 12-130 m/sec (27-280 mi/hr). Somatic nervous system
neurons.
•
Type B fibers. Small diameter, myelinated. Impulse conduction up to 15 m/sec (32 mi/hr). Autonomic nervous system.
•
Type C fibers. Small diameter, unmyelinated.
system.
•
Encoding of Stimulus Intensity The number of neurons stimulated. Frequency of impulses.
Impulse conduction from 0.5-2 m/sec (1-4 mi/hr). Autonomic nervous
34
Neurotransmitters and Neuromodulation
•
Classes of neurotransmitters
–
Neurotransmitters, various small organic compounds
–
Released at synaptic cleft
–
Approximately 100 known
–
Classified into major groups
–
Acetylcholine
–
•
excitatory or inhibitory neurotransmitter
•
released in both CNS and PNS
•
molecule released from motor neuron at neuromuscular junction
Amino acids
•
building blocks of proteins
•
some also neurotransmitters
•
e.g., glutamate, glycine, aspartate
Classes of neurotransmitters
–
–
•
•
Monoamines
•
derived from certain amino acids
•
carboxyl group removed and functional group added
•
subgroup added determines type
•
includes subgroup, catecholamines (norepinephrine, epinephrine, dopamine)
Neuropeptides
•
chains of amino acids
•
include enkephalins and somatostatin
•
Removal of neurotransmitters from the synaptic cleft
–
Temporary association between neurotransmitter and receptor
–
Necessary to eliminate molecule after stimulation
–
Can occur by degradation
•
neurotransmitter chemically inactivated in synaptic cleft
•
e.g., breakdown of ACh by acetylcholinesterase
Removal of neurotransmitters from the synaptic cleft
–
Can occur by reuptake
35
•
neurotransmitter reabsorbed by transport protein in presynaptic neuron
•
“recycled” into another synaptic vesicle for reuse
•
e.g., drugs, selective serotonin reuptake inhibitors
•
•
block reuptake of serotonin and used in treatment of depression
Neuromodulators
–
Chemical released from cells
–
Locally regulate or alter response of neurons to neurotransmitters
–
Release termed neuromodulation
–
Facilitation
•
occurs when greater response in postsynaptic neuron
•
may increase amount of neurotransmitter in synaptic cleft
•
may increase number of receptors on postsynaptic neurons
Neural Integration and Neuronal Pools of the CNS
•
Neuronal pools (neuronal circuits)
–
Complex patterns of grouped interneurons
–
Four types of circuits:
•
•
converging, diverging, reverberating, parallel-after-discharge
–
Pool may be localized or distributed in several regions of CNS
–
All restricted in number of input sources and output destinations
Types of circuits
–
–
–
Converging circuit
•
input that converges at a single postsynaptic neuron
•
e.g., multiple sensory neurons synapsing on neurons in salivary nucleus
•
causes salivary nucleus to alter activity of salivary glands
•
inputs originating from more than one stimulus
•
multiple inputs leading to single output: saliva production
Diverging circuit
•
spreads information from one presynaptic neuron to several postsynaptic neurons
•
e.g., neurons in the brain controlling movements of skeletal muscles
•
single or few inputs leading to multiple outputs
Reverberating circuits
36
•
utilize feedback to produce repeated, cyclical stimulation
•
once activated, may continue to function until cycle is broken
•
broken by inhibitory stimuli or synaptic fatigue
•
•
–
due to exhaustion of neurotransmitter in presynaptic cell
e.g., circuits that keep us breathing during sleep
Parallel-after-discharge circuits
•
input transmitted simultaneously along several pathways to common postsynaptic cell
•
vary in number of neurons in pathway
•
due to synaptic delay, signal arriving at postsynaptic cell at various times
•
believed to be involved in higher-order thinking
37