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Chapter 11

Nervous Tissue

Nervous System

•      The master controlling and communicating system of the body

•      Functions:

•    Sensory input – monitoring stimuli occurring inside and outside the body 

•    Integration – interpretation of sensory input

•    Motor output – response to stimuli by activating effector organs 

Organization of the Nervous System

•      Central nervous system (CNS)

•    Brain and spinal cord

•    Integration and command center

•      Peripheral nervous system (PNS)

•    Paired spinal and cranial nerves

•    Carries messages to and from the spinal cord and brain

Peripheral Nervous System (PNS):
Two Functional Divisions

•      Sensory (afferent) division

•    Sensory afferent fibers – carry impulses from skin, skeletal muscles, and joints to the brain

•    Visceral afferent fibers – transmit impulses from visceral organs to the brain

•      Motor (efferent) division

•    Transmits impulses from the CNS to effector organs

Motor Division: Two Main Parts

•      Somatic nervous system

•    Conscious control of skeletal muscles

•      Autonomic nervous system (ANS)

•    Regulate smooth muscle, cardiac muscle, and glands

•    Divisions – sympathetic and parasympathetic

Histology of Nerve Tissue

•      The two principal cell types of the nervous system are:

•    Neurons – excitable cells that transmit electrical signals

•    Supporting cells – cells that surround and wrap neurons

Supporting Cells: Neuroglia

•      The supporting cells (neuroglia or glia):

•    Provide a supportive scaffolding for neurons

•    Segregate and insulate neurons

•    Guide young neurons to the proper connections

•    Promote health and growth

Astrocytes

•      Most abundant, versatile, and highly branched glial cells

•      They cling to neurons and cover capillaries

•      Functionally, they:

•    Support and brace neurons

•    Anchor neurons to their nutrient supplies

•    Guide migration of young neurons

•    Control the chemical environment

Microglia and Ependymal Cells

•      Microglia – small, ovoid cells with spiny processes

•    Phagocytes that monitor the health of neurons

•      Ependymal cells – squamous- to columnar-shaped cells

•    They line the central cavities of the brain and spinal column

Oligodendrocytes, Schwann Cells,
and Satellite Cells

•      Oligodendrocytes – branched cells that wrap CNS nerve fibers

•      Schwann cells (neurolemmocytes) – surround fibers of the PNS

•      Satellite cells surround neuron cell bodies with ganglia

Neurons (Nerve Cells)

•      Structural units of the nervous system

•    Composed of a body, axon, and dendrites

•    Long-lived, amitotic, and have a high metabolic rate

•      Their plasma membrane functions in:

•    Electrical signaling

•    Cell-to-cell signaling during development

Nerve Cell Body (Perikaryon or Soma)

•      Contains the nucleus and a nucleolus

•      Major biosynthetic center

•      Focal point for the outgrowth of neuronal processes

•      There are no centrioles (hence its amitotic nature)

•      Well developed Nissl bodies (rough ER)

•      Axon hillock – cone-shaped area from which axons arise

Processes

•      Armlike extensions from the soma

•      Called tracts in the CNS and nerves in the PNS

•      There are two types: axons and dendrites

Dendrites of Motor Neurons

•      Short, tapering, and diffusely branched processes

•      They are the receptive, or input, regions of the neuron

•      Electrical signals are conveyed as graded potentials (not action potentials)

Axons: Structure

•      Slender processes of uniform diameter arising from the hillock

•      Long axons are called nerve fibers

•      Usually there is only one unbranched axon per neuron

•      Rare branches, if present, are called axon collaterals

•      Axonal terminal – branched terminus of an axon

Axons: Function

•      Generate and transmit action potentials

•      Secrete neurotransmitters from the axonal terminals

Myelin Sheath

•      Whitish, fatty (protein-lipid), segmented sheath around most long axons

•      It functions in:

•    Protection of the axon

•    Electrically insulating fibers from one another

•    Increasing the speed of nerve impulse transmission

Myelin Sheath and Neurilemma: Formation

•      Formed by Schwann cells in the PNS

•      A Schwann cell:

•    Envelopes an axon in a trough

•    Encloses the axon with its plasma membrane

•    Concentric layers of membrane make up the myelin sheath

•      Neurilemma – remaining nucleus and cytoplasm of a Schwann cell

Nodes of Ranvier (Neurofibral Nodes)

•      Gaps in the myelin sheath between adjacent Schwann cells

•      They are the sites where collaterals can emerge

Unmyelinated Axons

•      A Schwann cell surrounds nerve fibers but coiling does not take place

•      Schwann cells partially enclose 15 or more axons

Axons of the CNS

•      Both myelinated and unmyelinated fibers are present

•      Myelin sheaths are formed by oligodendrocytes

•      Nodes of Ranvier are widely spaced

•      There is no neurilemma

Regions of the Brain and Spinal Cord

•      White matter – dense collections of myelinated fibers

•      Gray matter – mostly soma and unmyelinated fibers

Neuron Classification

•      Structural: 

•    Multipolar

•    Bipolar

•    Unipolar

•      Functional: 

•    Sensory (afferent)

•    Motor (efferent)

•    Interneurons (association neurons)

Neurophysiology

•      Neurons are highly irritable

•      Action potentials, or nerve impulses, are:

•    Electrical impulses carried along the length of axons

•    Always the same regardless of stimulus

•    The underlying functional feature of the nervous system

Electrical Definitions

•      Voltage – measure (mV) of potential energy generated by separated charge

•      Potential difference – voltage measured between two points

•      Current (I) – the flow of electrical charge between two points

•      Resistance (R) – hindrance to charge flow

•      Insulator – substance with high electrical resistance

•      Conductor – substance with low electrical resistance

Electrical Current and the Body

•      Reflects the flow of ions rather than electrons

•      There is a potential on either side of membranes when:

•    The number of ions is different across the membrane

•    The membrane provides a resistance to ion flow

Role of Ion Channels

•      Types of plasma membrane ion channels:

•    Passive, or leakage, channels – always open

•    Chemically gated channels – open with binding of a specific neurotransmitter

•    Voltage-gated channels – open and close in response to membrane potential

Operation of a Gated Channel

•      Example: Na+-K+ gated channel

•      Closed when a neurotransmitter is not bound to the extracellular receptor

•    Na+ cannot enter the cell and K+ cannot exit the cell

Operation of a Gated Channel

•      Open when a neurotransmitter is attached to the receptor

•    Na+ enters the cell and K+ exits the cell

Operation of a Voltage-Gated Channel

•      Example: Na+ channel

•      Closed when the intracellular environment is negative

•    Na+ cannot enter the cell

Operation of a Voltage-Gated Channel

•      Open when the intracellular environment is positive

•    Na+ can enter the cell

Gated Channels

•      When gated channels are open:

•    Ions move quickly across the membrane

•    Movement is along their electrochemical gradients

•    An electrical current is created

•    Voltage changes across the membrane

Electrochemical Gradient

•      Ions flow along their chemical gradient when they move from an area of high concentration to an area of low concentration

•      Ions flow along their electrical gradient when they move toward an area of opposite charge

•      Electrochemical gradient – the electrical and chemical gradients taken together

Resting Membrane Potential (Vr)

•      The potential difference (–70 mV) across the membrane of a resting neuron

•      It is generated by different concentrations of Na+, K+, Cl-, and protein anions (A-)

•      Ionic differences are the consequence of:

•    Differential permeability of the neurilemma to Na+ and K+

•    Operation of the sodium-potassium pump

Membrane Potentials: Signals

•      Used to integrate, send, and receive information

•      Membrane potential changes are produced by:

•    Changes in membrane permeability to ions

•    Alterations of ion concentrations across the membrane

•      Types of signals – graded potentials and action potentials

Changes in Membrane Potential

•      Caused by three events:

•    Depolarization – the inside of the membrane becomes less negative

•    Repolarization – the membrane returns to its resting membrane potential

•    Hyperpolarization –the inside of the membrane becomes more negative than the resting potential

Graded Potentials

•      Graded potentials:

•    Are short-lived, local changes in membrane potential

•    Decrease in intensity with distance

•      Their magnitude varies directly with the strength of the stimulus

•      Sufficiently strong graded potentials can initiate action potentials

•      Voltage changes in graded potentials are decremental

•      Current is quickly dissipated due to the leaky plasma membrane

•    Can only travel over short distances

Action Potentials (APs)

•      A brief reversal of membrane potential with a total amplitude of 100 mV

•      Action potentials are only generated by muscle cells and neurons

•      They do not decrease in strength over distance

•      They are the principal means of neural communication

•      An action potential in the axon of a neuron is a nerve impulse

Action Potential: Resting State

•      Na+ and K+ channels are closed

•      Leakage accounts for small movements of Na+ and K+

•      Each Na+ channel has two voltage-regulated gates

•    Activation gates – closed in the resting state

•    Inactivation gates – open in the resting state

Action Potential: Depolarization Phase

•      Na+ permeability increases; membrane potential reverses

•      Na+ gates are opened; K+ gates are closed

•      Threshold – a critical level of depolarization (-55 to -50 mV)

•      At threshold, depolarization becomes self generating

Action Potential: Repolarization Phase

•      Sodium inactivation gates close

•      Membrane permeability to Na+ declines to resting levels

•      As sodium gates close, voltage sensitive K+ gates open

•      K+ exits the cell and internal negativity of the resting neuron is restored

Action Potential: Undershoot

•      Potassium gates remain open, causing an excessive efflux of K+

•      This efflux causes hyperpolarization of the membrane (undershoot)

•      The neuron is insensitive to stimulus and depolarization during this time

Action Potential: Role of the Sodium-Potassium Pump

•      Repolarization

•    Restores the resting electrical conditions of the neuron

•    Does not restore the resting ionic conditions

•      Ionic redistribution back to resting conditions is restored by the sodium-potassium pump

Phases of the Action Potential

•      1 – resting state

•      2 – depolarization
      phase

•      3 – repolarization
      phase

•      4 – undershoot

Propagation of an Action Potential (Time = 0ms)

•      Na+ influx causes a patch of the axonal membrane to depolarize

•      Positive ions in the axoplasm move toward the polarized (negative) portion of the membrane (bottom arrows in figure)

•      Sodium gates are shown as closing, open, or closed

Propagation of an Action Potential (Time = 1ms)

•      Ions of the extracellular fluid move toward the area of greatest negative charge

•      A current is created that depolarizes the adjacent membrane in a forward direction

•      The impulse propagates away from its point of origin

Propagation of an Action Potential (Time = 2ms)

•      The action potential moves away from the stimulus

•      Where sodium gates are closing, potassium gates are open and create a current flow

Threshold and Action Potentials

•      Threshold – membrane is depolarized by 15 to 20 mV

•      Established by the total amount of current flowing through the membrane

•      Weak (subthreshold) stimuli are not relayed into action potentials

•      Strong (threshold) stimuli are relayed into action potentials

•      All-or-none phenomenon – action potentials either happen completely, or not at all

Coding for Stimulus Intensity

•      All action potentials are alike and are independent of stimulus intensity

•      Strong stimuli can generate an action potential more often than weaker stimuli

•      The CNS determines stimulus intensity by the frequency of impulse transmission

Coding for Stimulus Intensity

•      Upward arrows – stimulus applied

•      Downward arrows – stimulus stopped

•      Length of arrows – strength of stimulus

•      Action potentials – vertical lines

Absolute Refractory Period

•      Time from the opening of the Na+ activation gates until the closing of inactivation gates

•      The absolute refractory period:

•    Prevents the neuron from generating an action potential

•    Ensures that each action potential is separate

•    Enforces one-way transmission of nerve impulses

Relative Refractory Period

•      The interval following the absolute refractory period when:

•    Sodium gates are closed

•    Potassium gates are open

•    Repolarization is occurring

•      The threshold level is elevated, allowing strong stimuli to increase the frequency of action potential events

Conduction Velocities of Axons

•      Conduction velocities vary widely among neurons

•      Rate of impulse propagation is determined by:

•    Axon diameter – the larger the diameter, the faster the impulse

•    Presence of a myelin sheath – myelination dramatically increases impulse speed

Saltatory Conduction

•      Current passes through a myelinated axon only at the nodes of Ranvier

•      Voltage regulated Na+ channels are concentrated at these nodes

•      Action potentials are triggered only at the nodes and jump from one node to the next

•      Much faster than conduction along unmyelinated axons

Multiple Sclerosis (MS)

•      An autoimmune disease that mainly affects young adults

•      Symptoms include visual disturbances, weakness, loss of muscular control, and urinary incontinence

•      Nerve fibers are severed and myelin sheaths in the CNS become nonfunctional scleroses

•      Shunting and short-circuiting of nerve impulses occurs

•      Treatments include injections of methylprednisolone and beta interferon 

Nerve Fiber Classification

•      Nerve fibers are classified according to:

•    Diameter

•    Degree of myelination

•    Speed of conduction

Synapses

•      A junction that mediates information transfer from one neuron:

•    To another neuron

•    To an effector cell

•      Presynaptic neuron – conducts impulses toward the synapse

•      Postsynaptic neuron – transmits impulses away from the synapse

Electrical Synapses

•      Electrical synapses:

•    Are less common than chemical synapses

•    Correspond to gap junctions found in other cell types

•    Contain intercellular protein channels

•    Permit ion flow from one neuron to the next

•    Are found in the brain and are abundant in embryonic tissue

Chemical Synapses

•      Specialized for the release and reception of neurotransmitters

•      Typically composed of two parts:

•    Axonal terminal of the presynaptic neuron, which contains synaptic vesicles

•    Receptor region on the dendrite(s) or soma of the postsynaptic neuron

Synaptic Cleft

•      Fluid-filled space separating the presynaptic and postsynaptic neurons

•      Prevent nerve impulses from directly passing from one neuron to the next

•      Transmission across the synaptic cleft:

•    Is a chemical event (as opposed to an electrical one)

•    Ensures unidirectional communication between neurons

Synaptic Cleft: Information Transfer

•      Nerve impulse reaches axonal terminal of the presynaptic neuron

•      Neurotransmitter is released into the synaptic cleft

•      Neurotransmitter crosses the synaptic cleft and binds to receptors on the postsynaptic neuron

•      Postsynaptic membrane permeability changes, causing an excitatory or inhibitory effect

Termination of Neurotransmitter Effects

•      Neurotransmitter bound to a postsynaptic neuron:

•    Produces a continuous postsynaptic effect

•    Blocks reception of additional “messages”

•    Must be removed from its receptor

•      Removal of neurotransmitters occurs when they:

•    Are degraded by enzymes

•    Are reabsorbed by astrocytes or the presynaptic terminals

•    Diffuse from the synaptic cleft

Synaptic Delay

•      Neurotransmitter must be released, diffuse across the synapse, and bind to receptor

•      Synaptic delay – time needed to do this (0.3-5.0 ms)

•      Synaptic delay is the rate-limiting step of neural transmission

Postsynaptic Potentials

•      Neurotransmitter receptors mediate changes in membrane potential according to:

•    The amount of neurotransmitter released

•    The amount of time the neurotransmitter is bound to receptor

•      The two types of postsynaptic potentials are:

•    EPSP – excitatory postsynaptic potentials

•    IPSP – inhibitory postsynaptic potentials

Excitatory Postsynaptic Potentials

•      EPSPs are graded potentials that can initiate an action potential in an axon

•    Use only chemically gated channels

•    Na+ and K+ flow in opposite directions at the same time

•      Postsynaptic membranes do not generate action potentials

Inhibitory Synapses and IPSPs

•      Neurotransmitter binding to a receptor at inhibitory synapses:

•    Causes the membrane to become more permeable to potassium and chloride ions

•    Leaves the charge on the inner surface negative

•    Reduces the postsynaptic neuron’s ability to produce an action potential

Summation

•      A single EPSP cannot induce an action potential

•      EPSPs must summate temporally or spatially to induce an action potential

•      Temporal summation – presynaptic neurons transmit impulses in rapid-fire order

•      Spatial summation – postsynaptic neuron is stimulated by a large number of terminals at the same time

•      IPSPs can also summate with EPSPs, canceling each other out

Neurotransmitters

•      Chemicals used for neuronal communication with the body and the brain

•      50 different neurotransmitter have been identified

•      Classified chemically and functionally

Chemical Neurotransmitters

•      Acetylcholine (ACh)

•      Biogenic amines

•      Amino acids

•      Peptides

•      Novel messengers

Neurotransmitters: Acetylcholine

•      First neurotransmitter identified, and best understood

•      Released at the neuromuscular junction

•      Synthesized and enclosed in synaptic vesicles

•      Degraded by the enzyme acetylcholinesterase (AChE)

•      Released by:

•    All neurons that stimulate skeletal muscle

•    Some neurons in the autonomic nervous system

Neurotransmitters: Biogenic Amines

•      Include:

•    Catecholamines – dopamine, norepinephrine (NE), and epinephrine

•    Indolamines – serotonin and histamine

•      Broadly distributed in the brain

•      Play roles in emotional behaviors and our biological clock

Synthesis of Catecholamines

•      Enzymes present in the cell determine length of biosynthetic pathway

•      Norepinephrine and dopamine are synthesized in axonal terminals

•      Epinephrine is released by the adrenal medulla

Neurotransmitters: Amino Acids

•      Include:

•    GABA – Gamma (g)-aminobutyric acid

•    Glycine

•    Aspartate

•    Glutamate

•      Found only in the CNS

Neurotransmitters: Peptides

•      Include:

•    Substance P – mediator of pain signals

•    Beta endorphin, dynorphin, and enkephalins

•      Act as natural opiates, reducing our perception of pain

•      Bind to the same receptors as opiates and morphine

•      Gut-brain peptides – somatostatin, vasoactive intestinal peptide (VIP), and cholecystokinin

Novel Messengers

•      ATP

•    Found in both the CNS and PNS

•    Produces fast excitatory responses

•      Nitric oxide (NO)

•    Activates the intracellular receptor guanylyl cyclase

•    Is involved in learning and memory

•      Carbon monoxide (CO) is a main regulator of cGMP in the brain

Functional Classification of Neurotransmitters

•      Two classifications: excitatory and inhibitory

•    Excitatory neurotransmitters cause depolarizations
(e.g., glutamate)

•    Inhibitory neurotransmitters cause hyperpolarizations
(e.g., GABA and glycine)

•      Some neurotransmitters have both excitatory and inhibitory effects

•    Determined by the receptor type of the postsynaptic neuron

•    Example: aceytylcholine

•   Excitatory at neuromuscular junctions

•   Inhibitory with cardiac muscle

Neurotransmitter Receptor Mechanisms

•      Direct: neurotransmitters that open ion channels

•    Promote rapid responses

•    Examples: ACh and amino acids

•      Indirect: neurotransmitters that act through second messengers

•    Promote long-lasting effects

•    Examples: biogenic amines and peptides

Channel-Linked Receptors

•      Composed of integral membrane protein

•      Mediate direct neurotransmitter action

•      Action is immediate, brief, simple, and highly localized

•      Ligand binds the receptor, and ions enter the cells

•      Excitatory receptors
depolarize membranes

•      Inhibitory receptors
hyperpolarize
membranes

G Protein-Linked Receptors

•      Responses are indirect, slow, complex, prolonged, and often diffuse

•      These receptors are transmembrane protein complexes

•      Examples: muscarinic ACh receptors, neuropeptides, and those that bind biogenic amines

G Protein-Linked Receptors: Mechanism

•      Neurotransmitter binds to G protein-linked receptor

•      G protein is activated and GTP is hydrolyzed to GDP

•      The activated G protein complex activates adenylate cyclase 

•      Adenylate cyclase catalyzes the formation of cAMP from ATP

•      cAMP, a second messenger, brings about various cellular responses

G Protein-Linked Receptors: Effects

•      G protein-linked receptors activate intracellular second messengers including Ca2+, cGMP, diacylglycerol, as well as cAMP

•      Second messengers:

•    Open or close ion channels

•    Activate kinase enzymes

•    Phosphorylate channel proteins

•    Activate genes and induce protein synthesis

Neural Integration: Neuronal Pools

•      Functional groups of neurons that:

•    Integrate incoming information

•    Forward the processed information to its appropriate destination

•      Simple neuronal pool

•    Input fiber – presynaptic fiber

•    Discharge zone – neurons most closely associated with the incoming fiber

•    Facilitated zone – neurons farther away from incoming fiber

Types of Circuits in Neuronal Pools

•      Divergent – one incoming fiber stimulates ever increasing number of fibers, often amplifying circuits

•      Convergent – opposite of divergent circuits, resulting in either strong stimulation or inhibition

•      Reverberating – chain of neurons containing collateral synapses with previous neurons in the chain

•      Parallel after-discharge – incoming neurons stimulate several neurons in parallel arrays

Patterns of Neural Processing

•      Serial Processing

•    Input travels along one pathway to a specific destination

•    Works in an all-or-none manner

•    Example: spinal reflexes

•      Parallel Processing

•    Input travels along several pathways

•    Pathways are integrated in different CNS systems

•    One stimulus promotes numerous responses

•      Example: a smell may remind one of the odor and associated experiences

Development of Neurons

•      The nervous system originates from the neural tube and neural crest

•      The neural tube becomes the CNS

•      There is a three-phase process of differentiation:

•    Proliferation of cells needed for development

•    Migration – cells become amitotic and move externally

•    Differentiation into neuroblasts

•      The nervous system originates from the neural tube and neural crest

•      The neural tube becomes the CNS

•      There is a three phase process of differentiation:

•    Proliferation of cells needed for development

•    Migration – cells become amitotic and move externally

•    Differentiation into neuroblasts

Axonal Growth

•      Guided by:

•    Scaffold laid down by older neurons

•    Orienting glial fibers

•    Release of nerve growth factor by astrocytes

•    Neurotropins released by other neurons

•    Inhibiting factors (axons avoid these areas) such as RGM and SLIT

N-CAMs

•      N-CAM – nerve cell adhesion molecule

•      Important in establishing neural pathways

•      Without N-CAM, neural function is impaired

•      Found in the membrane of the growth cone