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 (V_r)

• 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