Neuro Anatomymicroscopis I

Bambang Soemantri

• Nervous system– Swift, brief responses to stimuli

• Endocrine system– Adjusts metabolic operations– Directs long-term changes

Two organ systems coordinate and direct activities of body

Anatomical Organization of the Nervous system

• Central Nervous system :– Brain– Spinal cord

• Peripheral nervous system– Ganglion– Cranial nerves– Spinal nerves

• PNS further subdivided into: – Sensory division and Motor division

• Motor division further subdivided into: – Somatic and Autonomic

• Autonomic further subdivided into: – Sympathetic and Parasympathetic

Blue arrows: afferent signals Red arrows: efferent signals

An Overview of the Nervous System

Nervous system includes all neural tissue in body

• Central Nervous System– Brain and spinal cord

• Peripheral Nervous System– All neural tissue outside CNS

Functional divisions of nervous system

• Afferent– Sensory information from receptors to CNS

• Efferent – Motor commands to muscles and glands– Somatic division

• Voluntary control over skeletal muscle– Autonomic division

• Involuntary regulation of smooth and cardiac muscle, glands

Histology of Neural Tissue

• Neurons

Cells in Nervous Tissue

• Neuroglia

• about half the volume of cells in the CNS• smaller than neurons• 5 to 50 times more numerous• do NOT generate electrical impulses• divide by mitosis• Four types in the CNS

– Astrocytes– Oligodendrocytes– Microglia– Ependymal cells

Neuroglia (Glia)

Neuroglia (Neuroglial Cells)Neuroglia (Neuroglial Cells)

Central NeurogliaCentral Neuroglia AstrocyteAstrocyte protoplasmic astrocyteprotoplasmic astrocyte fibrous astrocytefibrous astrocyte OligodendrocyteOligodendrocyte perineuronal satellite cellperineuronal satellite cell interfascicular cellinterfascicular cell MicrogliaMicroglia Ependymal CellEpendymal Cell

Peripheral NeurogliaPeripheral Neuroglia Schwann CellSchwann Cell in peripheral nervein peripheral nerve and ganglionand ganglion Capsular (Satellite) CellCapsular (Satellite) Cell in ganglionin ganglion

AstrocyteAstrocyte Oligodendrocyte Oligodendrocyte Microglia Microglia

Central Central NeurogliaNeuroglia

• Largest of glial cells• Most numerous• Star shaped with many processes projecting from the cell body• Help form and maintain blood-brain barrier• Provide structural support for neurons• Maintain the appropriate chemical environment for generation of nerve impulses/action potentials• Regulate nutrient concentrations for neuron survival• Regulate ion concentrations - generation of action potentials by neurons• Take up excess neurotransmitters• Assist in neuronal migration during brain development• Perform repairs to stabilize tissue

Astrocytes

AstrocyteAstrocyte

• Protoplasmic Astrocyte: Gray Matter Protoplasmic Astrocyte: Gray Matter • Fibrous Astrocyte: White MatterFibrous Astrocyte: White Matter

Cell BodyCell Body ‘‘potato’ shape nucleus, scarse pale cytopasmpotato’ shape nucleus, scarse pale cytopasmProcessesProcesses - - GFAP GFAP (glial fibroacidic protein):(glial fibroacidic protein): intermediate filament intermediate filament -- Perivascular Feet Perivascular Feet (Foot Process, Vascular End-Feet)(Foot Process, Vascular End-Feet) surrounding blood vesselssurrounding blood vessels

Specialized AstrocytesSpecialized Astrocytes - Bergmann’s gial cell, Muller cell, pituicyte- Bergmann’s gial cell, Muller cell, pituicyte

Oligodendrocytes

• Most common glial cell type

• Each forms myelin sheath around the axons of neurons in CNS

• Analogous to Schwann cells of PNS

• Form a supportive network around CNS neurons

• fewer processes than astrocytes• round or oval cell body

Microglia

• Small cells found near blood vessels• Phagocytic role - clear away dead cells• protect CNS from disease through phagocytosis of

microbes• migrate to areas of injury where they clear away debris

of injured cells - may also kill healthy cells

• few processes• derived from mesodermal cells that also give rise to monocytesand macrophages

Ependymal Cells

• Form epithelial membrane lining cerebral cavities (ventricles) & central canal - that contain CSF

• Produce & circulate the cerebrospinal fluid (CSF) found in these chambers

• CSF = colourless liquid that protects the brain and SC against chemical & physical injuries, carries oxygen, glucose and other

necessary chemicals from the blood to neurons and neuroglia

• epithelial cells arranged in asingle layer• range in shape from cuboidalto columnar

• Flat cells surrounding PNS axons• Support neurons in the PNS

PNS: Satellite Cells

PNS: Schwann Cells

• each cell surrounds multiple unmyelinated PNS axons with a single layer of its plasma membrane

• Each cell produces part of the myelin sheath surrounding an axon in the PNS

• contributes regeneration of PNS axons

Neurons

•have the property of electrical excitability - ability to produceaction potentials or impulses in response to stimuli

•what is the main defining characteristic of neurons?

Representative Neuron

1. cell body or soma -single nucleus with prominent nucleolus-Nissl bodies

-rough ER & free ribosomes for protein synthesis-proteins then replace neuronal cellular components for growthand repair of damaged axons in the PNS

-neurofilaments or neurofibrils give cell shape and support - bundles of intermediate filaments-microtubules move material inside cell-lipofuscin pigment clumps (harmless aging) - yellowish brown

2. Cell processes = dendrites (little trees)- the receiving or input portion of the neuron-short, tapering and highly branched-surfaces specialized for contact with other neurons-cytoplasm contains Nissl bodies & mitochondria

Neurons

3. Cell processes = axons• Conduct impulses away from cell body-

propagates nerve impulses to another neuron

• Long, thin cylindrical process of cell • contains mitochondria, microtubules &

neurofibrils - NO ER/NO protein synth.• joins the soma at a cone-shaped

elevation = axon hillock• first part of the axon = initial segment • most impulses arise at the junction of the

axon hillock and initial segment = trigger zone

• cytoplasm = axoplasm• plasma membrane = axolemma• Side branches = collaterals arise from

the axon• axon and collaterals end in fine

processes called axon terminals• Swollen tips called synaptic end bulbs

contain vesicles filled with neurotransmitters

Axonal Transport• Cell body is location for most protein synthesis

– neurotransmitters & repair proteins • however the axon or axon terminals require proteins

– e.g. neurotransmitters• Axonal transport system moves substances

– slow axonal flow• movement of axoplasm in one direction only -- away from cell

body• movement at 1-5 mm per day • replenishes axoplasm in regenerating or maturing neurons

– fast axonal flow• moves organelles & materials along surface of microtubules• at 200-400 mm per day• transports material in either direction• for use in the terminals or for recycling in cell body

Components of Axonal (Axoplasmic) TransportComponents of Axonal (Axoplasmic) Transport

Components Velocity (mm/day) Transporting Components Velocity (mm/day) Transporting SubstancesSubstances

Anterograde Axonal TransportAnterograde Axonal Transport Fast Transport Fast Transport 200-400200-400 synaptic vesicle, enzymes neurotransmitters Mitochondrial Transport 50-10050-100 mitochondria Slow TransportSlow Transport Slow Components a (SCa) 0.1 - 1.00.1 - 1.0 tubulin, neurofilament protein Slow Comnponent b (SCb) 2 - 62 - 6 actin, clathrine, calmodulins spectrin, cytoplasmic enzymes Retrograde Axonal Transport Retrograde Axonal Transport 100-200100-200 prelysosomal vesicles, recycled proteins, HRP, neurotrophic viruses

Axonal (Axoplasmic) TransportAxonal (Axoplasmic) Transport

Mechanism ofMechanism of Axonal Axonal TransportTransport

FastFast AnterogradeAnterograde Axonal transportAxonal transport

andand RetrogradeRetrograde Axonal transportAxonal transport

Functional Classification of Neurons

• Sensory (afferent) neurons– transport sensory information from skin, muscles,

joints, sense organs & viscera to CNS• Motor (efferent) neurons

– send motor nerve impulses to muscles & glands• Interneurons (association) neurons

– connect sensory to motor neurons– 90% of neurons in the body

• Afferent division of PNS• Deliver sensory information from sensory receptors to CNS

– free nerve endings: bare dendrites associated with pain, itching, tickling, heat and some touch sensations

– Exteroceptors: located near or at body surface, provide information about external environment

– Proprioceptors: located in inner ear, joints, tendons and muscles, provide information about body position, muscle length and tension,

position of joints– Interoceptors: located in blood vessels, visceral organs and NS -provide information about internal environment

-most impulses are not perceived – those that are, are interpreted as pain or pressure

Sensory Neurons

Sensory Neurons• Sensory receptors cont…

– mechanoreceptors: detect pressure, provide sensations of touch, pressure, vibration, proprioception, blood vessel stretch, hearing and equilibrium

– thermoreceptors: detect changes in temperature– nociceptors: respond to stimuli resulting from damage (pain)– photoreceptors: light– osmoreceptors: detect changes in OP in body fluids– chemoreceptors: detect chemicals in mouth (taste), nose (smell)

and body fluids

-analgesia: relief from pain-drugs: aspirin, ibuprofen – block formation of prostaglandins that stimulate the nociceptors -novocaine – block nerve impulses along pain nerves-morphine, opium & derivatives (codeine) – pain is felt but not perceived in brain (blocks morphine and opiate receptors in pain centers)

• Efferent pathways• Stimulate peripheral structures

– Somatic motor neurons• Innervate skeletal muscle

– Visceral motor neurons• Innervate all other peripheral effectors• Preganglionic and postganglionic neurons

Motor Neurons

Motor Units• Each skeletal fiber has only ONE

NMJ• MU = Somatic neuron + all the

skeletal muscle fibers it innervates• Number and size indicate

precision of muscle control• Muscle twitch

– Single momentary contraction– Response to a single stimulus

• All-or-none theory – Either contracts completely or not

at all

• Muscle fibers of different motor units are intermingled so that net distribution of force applied to the tendon remains constant even when individual muscle groups cycle between contraction and relaxation.

• Motor units in a whole muscle fire asynchronouslysome fibers are active others are relaxed delays muscle fatigue so contraction can be sustained

Structural Classification of Neurons

• Based on number of processes found on cell body– multipolar = several dendrites & one axon

• most common cell type in the brain and SC

– bipolar neurons = one main dendrite & one axon• found in retina, inner ear & olfactory

– unipolar neurons = one process only, sensory only (touch, stretch)• develops from a bipolar neuron in the embryo - axon and dendrite fuse and then

branch into 2 branches near the soma - both have the structure of axons (propagate APs) - the axon that projects toward the periphery = dendrites

• Named for histologist that first described them or their appearance

Structural Classification of Neurons

•Purkinje = cerebellum•Renshaw = spinal cord

• others are named for shapese.g. pyramidal cells

Classification of neurons by cell size

• 1. golgi type I :– Neurons have a long axon and large soma

• 2. Golgy type II :– Neurons have short axon undergoes

extensive terminal aeborization and small soma

The Nerve Impulse

Continuous versus Saltatory Conduction

• Continuous conduction (unmyelinated fibers)– An action potential spreads

(propagates) over the surface of the axolemma

– as Na+ flows into the cell during depolarization, the voltage of adjacent areas is effected and their voltage-gated Na+ channels open

– step-by-step depolarization of each portion of the length of the axolemma

Saltatory Conduction

• Saltatory conduction-depolarization only at nodes of Ranvier - areas along the axon that are unmyelinated and where there is a high density of voltage-gated ion channels

-current carried by ions flows through extracellular fluid from node to node

• Properties of axon• Presence or absence of myelin sheath

• Diameter of axon

Rate of Impulse Conduction

MyelinMyelin

Conduction velocityConduction velocity is proportional to is proportional to1. The Length of Internodal Segment1. The Length of Internodal Segment2. Thickness of Myelin2. Thickness of Myelin3. Diameter of Nerve Fiber3. Diameter of Nerve Fiber

Synaptic Communication

• Synapse– Site of intercellular communication

between 2 neurons or between a neuron and an effector (e.g. muscle)

• Originates in the soma• Travels along axons• Permit communication between neurons

and other cells– Initiating neuron = presynaptic neuron– Receiving neuron = postsynaptic

neuron• Most are axodendritic axon -> dendrite• Some are axoaxonic – axon > axon

Synapse

Tipes of synapses

• Axodendritic:– Between an axon and a dendrite

• Axosomatic:– Between an axon and a soma

• Axoaxonic:– Between two axon

• Dendrodendritic:– between two dendrites

Synaptic morphology

• Presynaptic membrane:– Contains metochondria, a few elements of

SER, and an abundance of synaptic vesicles.• Synaptic cleft• Postsynaptic membrane:

– Contains neorotransmitter receptors

SYNAPSE

Ÿ Presynaptic Portion: Synaptic Button - synaptic vesicle - mitochondria - presynaptic membrane: tubulin

Ÿ Synaptic Cleft - 20-30 nm Ÿ Postsynaptic Portion - postsynaptic membrane: actin, fodrin, spectrin - mitochondria

SYNAPSE

Impuls transmission at synapse can occur:

• Electrically • Chemically

VIEW OF THE CHEMICAL SYNAPSE & FUNCTION

Neurotransmitters

• Are signaling molecules that are released at the presynaptic membranes and activate receptors on postsynaptic membranes.

• More than 100 identified• Some bind receptors and cause channels to

open• Others bind receptors and result in a second

messenger system• Results in either excitation or inhibition of the

target• Represented by three groups:

– Small molecules transmitters– Neuropeptides– Gases

Neurotransmitters

• Small molecule neurotransmitter :– Acetylcholine– Amino acids : Glutamat, Aspartat, GABA– Biogenic amines : modified amino acids

• Catecholamines : Epinephrine, NE, Dopamine• Serotonin

• Neuropeptides :– Substane P; Opoid peptides (endorphine,

enkephaline, dynorphines); hypothalamic releasing hormones; hormones stored in and release from neurohypophyse

• Gases : NO and CO

Removal of Neurotransmitter

• Diffusion– move down concentration gradient

• Enzymatic degradation– acetylcholinesterase

• Uptake by neurons or glia cells– neurotransmitter transporters

• NE, epinephrine, dopamine, serotonin

Peripheral nervous system • The PNS includes the peripheral nerves

and nerve cell bodies located outside the CNS

• Peripheral nerves are bundles of nerve fibers (axons) located outside the CNS and surrounded by connective tissue sheaths. These bundles (fascicles) may be observed with the unaided eye. Usually, each bundles has both sensory and motor components.

Peripheral Nerve

Nerve Fiber Myelinated Nerve Fiber Axon, Myelin sheath, Schwann cell, Schwann cell

Unmyelinated Nerve Fiber Unmyelinated Nerve Fiber Axon, Schwann cellAxon, Schwann cell

Connective Tissue SheathConnective Tissue Sheath EndoneuriumEndoneurium Perineurium – blood vesselsPerineurium – blood vessels EpineuriumEpineurium

Composition of Peripheral NerveComposition of Peripheral Nerve

Connective tissue investment

• Connective tissue investments of peripheral nerves include the:– Epineurium– Perineurium– Endoneurium

Epineurium

• Is the outermost layer• Is composed of dense irregular,

collagenous connective tissue containing thick elastic fibers that completely ensheathe the nerve. Collagen fibers within the sheath are aligned and oriented to prevent damage by overstretching of the nerve bundle.

Perineurium

• The middle layer of connective tissue investments, covers each bundle of nerve fibers (fascicle) within the nerve.

• Composition:– Dense connective tissue but is thinner

than epineurium.

Endoneurium • The innermost layer connective tissue

investment of a nerve, surrounds individual nerve fibers (axons).

• Is a loose connective tissue composed of a thin layer of reticular fibers (produced by Schwann cells), scattered fibroblasts, macrophages, and mast cells.

• The endoneurium is in contact with the basal lamina of the Schwann cells.

Somatic motor and autonomic nervous systems

• Functionally, the motor component is divided into the somatic and autonomic nervous systems

• The somatic nerves systems provides motor impulses to the skeletal muscles

• The autonomic nerves systems provides motor impulses to the smooth muscles of the viscera, cardiac muscle and secretory cells of the exocrine and endocrine glands.

Motor component of the somatic nervous system

• Motor innervation to skeletal muscle is provided by somatic nerves from spinal and selected cranial nerves.

• The cell bodies of these nerve fibers originate in the CNS

Autonomic nervous system = ANS(involuntary , visceral)

• Is generally defined as a motor system.• Controls the viscera of the body by

supplying the general visceral efferent (visceral motor) component to smooth muscle, cardiac muscle, and glands.

• The autonomic nervous system possesses two neurons between the CNS and the effector organ.

• Cell bodies of the first neuron lie in the CNS and their axons are usually myelinated.

• These preganglionic fibers (axons) seek an autonomic ganglion located outside the CNS, where they synapse on multipolar cell bodies of postganglionic neurons.

• Postganglionic fibers usually unmyelinated although they always are enveloped by Schwann cells, exit the ganglion to terminate on the effector organ.

• The ANS is subdivided into two functionally deferent divisions:

– The sympathetic nervous system

– The parasympathetic nervous system

Ganglia

• Are aggregations of cell bodies of neurons located outside the CNS, there are two types of ganglia:– Sensory– Autonomic

Sensory ganglia• Sensory ganglia house cells bodies of

sensory neurons.• Cell of the sensory ganglia are

pseudounipolar which enveloped by cuboidal capsule cells. These capsule cells are surrounded by connective tissue capsule composed of satellite cells and collagen.

Autonomic ganglia

• Autonomic ganglia house cells bodies of postganglionic autonomic nerves.

• Nerve cells bodies of autonomic ganglia are motor in function.

Central nervous system

• The CNS, composed of : the brain and the spinal cord, consist of :

white matter and gray matter without intervening connective tissue elements ; therefore, the CNS has the consistency of a semifirm gel.

Continued

• White matter is composed mostly of myelineted fibers a long with some unmyelineted fibers and neoroglial cells.

• Gray matter is consist of aggregation of neuronal cells bodies, dendrites, and unmyelineted portion of axons as well as neuroglial cells.

• Gray matter in the brain is located at the periphery (cortex) of the cerebrum and cerebellum. Whereas the white matter lies deep to the cortex and surrounds the basal ganglia.

continued

• Spinal cord:– White matter is located in the periphery,

whereas grey matter lies deep in the spinal cord, where it forms an H shape in cross section.

– Central canal lined by ependymal cells.

Meninges

• Are three connective tissue covering the brain and spinal cord.

• Meninges consist of:– Dura mater : the outermost layer– Arachnoid : the intermediate layer– Pia mater : the innermost layer

Dura mater• The dura mater is the dense outermost layer

of the meninges.• Cerebral dura:

– Is a dense, collagenous CT composed of two layers that are closely apposed in the adult.

– 1. Periosteal dura mater, the outer layer, is composed of osteoprogenitor cells, fibroblast and collagen fibers. Periosteal dura mater serves periosteum of the inner surface of the skull, and as such it is well vascularized.

Dura mater

Strongest2 layers :

- Periosteal- MeningealLayers fuse except at dural sinuses

Dura mater

Layers fused except at sinusesForms :

- Falx cerebri - Falx cerebelli - Tentorium cerebelli

continued

2. Meningeal dura :– Inner layer of the dura is composed of fibroblast

and collagen fibers.– This layer contains small blood vessels– Internally meningeal dura covered by a layer of

cells called border cell layer, is composed of fibroblast.

Spinal dura mater Does not adhere to the walls of the vertebral canal. The epidural space : the space between the dura

and the bony walls of the vertebral canal, is filled with epidural fat and a venous plexus.

Arachnoid• Is the intermediate layer of the meninges.• Is avascular although blood vessels course

through it.• It consist of fibroblast, collagen, and some

elastic fibers.• Subdural space located between dura and

arachnoid, is a potential space because it appears only after injury resulting subdural hemorrhage

continued

• In certain regions the arachnoid extend through the dura to form arachnoid villi, which protrude into the dural venous sinuses. The function of the arachnoid villi is transporting CSF from the subarachnoid spaces into the venous system.

Arachnoid mater

* Arachnoid Villi Projections through duraPass into superior sagittal sinus Passage of CSF

* Web-like attachments to pia

Arachnoid mater

• Spaces– Subdural

• Between dura and arachnoid• Little CSF

– Subarachnoid • between arachnoid and pia• CSF and blood vessels

Pia mater

• Is the innermost highly vascular layer of the meninges, is in close contact with the brain, following closely all of its contours.

• The pia mater does not contact with the neural tissue because a thin layer of neuroglial processes is always interposed between them.

continued

• Composition : a thin layer of flatened, modified fibroblast.

• Blood vessels, abundant in this layer, are surrounded by pia cells interspersed with macrophage, mast cells, and lymphocytes.

• The pia mater is completely separated from the underlying neural tissue by neuroglial cells.

• Blood vessels penetrate the neural tissue and are covered by pia mater until they form the continuous capillaries characteristic of the CNS.

• Pedicels of the astrocytes, cover capillaries within the neural tissue.

Pia mater

* Delicate* Vascular* Clings to surface of brain

Blood-brain barrier

• Endothelial cells of CNS capillaries prevent the free passage of selective blood-borne substances into the neural tissue.

• This barrier is established by the endothelial cells lining the continuous capillaries that course through the CNS.

• These endothelial cells form zonula occludentes with one another, retarding the flow of material between cells.

continued

• These endothelial cells have relatively few pinocytotic vesicles and vesicular traffic is almost completely restricted to receptor mediated transport.

Choroid plexus

• Are formed by folds of pia mater contain abundant of fenestrated capillaries and invested by the simple cuboidal (ependymal) lining extend into the third, fourth, and lateral ventricles of the brain.

• Are produced CSF.

Cerebrospinal fluid

• Cerebrospinal fluid bathes, nourishes, and protects the brain and spinal cord.

• Is produces by the choroid plexus.

CSF • Contains– Sodium– Chloride– Magnesium– Protein– Glucose– Oxygen

• Functions– Cushion– Waste removal– Nourish brain

Production of CSF

• Formed in choroid plexuses– Rich capillary beds

in pia surrounded by ependymal cells

• Filtrate of blood plasma from capillaries

Flow of CSF• Choroid

plexus• Ventricles• Subarachnoid

space through lateral and median apertures of 4th ventricle

• Blood of dural sinuses via arachnoid villi

Cerebral cortex• Is responsible for learning, memory,

sensory integration, information analysis, and initiation of motor responses.

• Is divided into six layers as follows:1. Molecular layer : contains horizontal cells

and neuroglia 2. External granular layer : contains mostly

granule(stellate) cells and neuroglial cells

continued

3. External pyramidal layer : contains pyramidal cells and neuroglial cells.

4. Internal granular layer contains small granule cells (stelate cells), pyramidal cells, and neuroglia.

5. Internal pyramidal layer contains larges pyramidal cells and neuroglia

6. Multiform layer consist of various shapes (Martinotti cells), and neuroglia.

Cerebellar cortex

• Is responsible for balance, equilibrium, muscle tone, and muscle coordination.

• Is divided into three layers:1. Molecular layer, lies directly below the

pia mater.2. Purkinje cell layer, contains the large,

flask-shaped Purkinje cells, which are present only in the cerebellum.

3. Granular layer, consist of small cells and glomeruli (cerebellar islands).

Neural Regeneration

Nerve regeneration

• Nerve cells, unlike neuroglial cells, cannot proliferate but can regenerate their axons, located in the PNS.

• When a traumatic event destroy neurons, they are not replaced because neurons cannot proliferate ; therefore the damage to the CNS is permanent.

continued

• However, if a peripheral nerve fiber is injured or transected, the neurons attempts to repair the damage, regenerate the process, and restore function by initiating a series of structural and metabolic events, collectively called the axon reaction.

Axon reaction

• The reactions to the trauma are characteristically localized in three regions of the neurons:

1. Local changes: at the site of damage.2. Anterograde changes: distal to the site of

damage3. Retrograde changes: proximal to the site of

damage.

Local reaction• Local reaction to injury involves repair and

removal of debris by neuroglial cells.• The severed ends of the axon retract away from

each other, and the cut membrane of each stump fuses to cover the open end, preventing loss of axoplasm.

• Macrophages and fibroblast infiltrate the damaged area, secrete cytokines and growth factors, and up-regulate the expression of receptors.

• Macrophages invade the basal lamina and assisted by Schwann cells, phagocytose the debris.

Human Anatomy, 3rd editionPrentice Hall, © 2001

Neural Regeneration

Anterograde reaction• In the anterograde reaction process,

that portion of the axon distal to an injury undergoes degeneration and is phagocytosed

• The axon undergoes anterograde changes as follows:

1. The axon terminal becomes hypertrophied and degeneretes within a week. Schwann cells prolivered and phagocitose the remnants of the axon terminal, and the newly formed Schwann cells occupy the synaptic space.

Continued

– 2. The distal portion of the axon undergoes Wallerian degeneration, distal to the lesion, the axon and the myelin disintegrate, Schwann cells dedifferentiate and myelin synthesis is discontinued. Macrophages and Schwann cells phagocytose the disintegrated remnants

– 3. Schwann cells proliferate, forming a column of Schwann cells ( Schwann tubes ) enclosed by the original basal lamina of the endoneurium.

Human Anatomy, 3rd editionPrentice Hall, © 2001

Neural Regeneration

Human Anatomy, 3rd editionPrentice Hall, © 2001

Neural Regeneration

Human Anatomy, 3rd editionPrentice Hall, © 2001

Neural Regeneration

Human Anatomy, 3rd editionPrentice Hall, © 2001

Neural Regeneration

Retrograde reaction and regeneration• In these process, the proximal portion of the

injured axon undergoes degeneration followed by sprouting of a new axon whose growth is directed by Schwann cells.

• The portion of the axon proximal to the damage undergoes the following changes :– 1. the perikaryon of the damaged neuron becomes

hypertrophied, its Nissl bodies disperse, and its nucleus is displaced ( these events called chromatolysis). The soma is actively producing free ribosomes and synthesizing proteins and various macromolecule.

continued

– 2. Several “sprouts” of axon emerge from the proximal axon stump, enter the endoneurium, and are guided by the Schwann cells to their target cell. For regeneration to occur, the Schwann cells, macrophages, and fibroblasts as well as the basal lamina must be present. These cells manufacture growth factors and cytokines and up-regulate the expression for the seceptors of these signaling molecules.

continued

– 3. the sprout is guided by the Schwann cells that redifferentiate and either begin to manufacture myelin around the growing axon or, in nonmyelinated axons, form a Schwann cell sheath. The sprout that reaches the target cell first form a synapse, whereas the other sprout degenerate.

Regeneration in the CNS• Injured cells within the CNS are

phagocytosed by microglia, and the space liberated by the phagocytosis is occupied by proliferation of glial cells, which form a cell mass called glial scar.

• Limited ability in PNS• Severed peripheral nerve successfully

regenerates a fraction of the axons– Function is permanently impaired– Schwann cells participate

• Wallerian degeneration– Loss of axon distal to damage

Regeneration

• More complicated than PNS regeneration• Far more limited • More axons involved• Astrocytes produce scar tissue preventing

axonal regrowth• Astrocytes release chemicals blocking

regrowth

Regeneration in CNS

Nerve ending – nerve terminal• Two structural type :

– 1. Motor ending terminal of axon )• Transmit impulses from the CNS to skeletal &

smooth muscle & to glands ( secretory ending)– 2. sensory ending = sensory receptor =

terminal of dendrites :• Perceive various stimuli and transmit this input

to the CNS

continued

• These sensory receptor are classified into three type depending on the source of the stimulus, and are components of the general or special somatic and visceral afferent pathway :– Exteroceptors– Proprioceptors– interoceptors

Exteroceptors

• Location : near the body surface• Specialized to perceive stimuli from the

external environment• These receptors sensitive to :

– Temperature– Touch– Pressure and– Pain

• Are component of the general somatic afferent

continued

• Special somatic afferent :– Specialized for light ( sense of vision) and

sound (sense of hearing)

• Special visceral afferent modality :– Specialized for smell and taste

Proprioceptors

• Are specialized receptor located in joint capsules, tendon and intrafusal fibers within muscle.

• These general somatic afferent receptors transmit sensory input to the CNS, which translated into information that relates to an awareness of the body in space and movement

continued

• Vestibular (balance) mechanism, located within the inner ear, are specialized for receiving stimuli related to motion vectors within the head.

Interoceptors • Are specialized receptors that perceive

sensory information from within organs of the body.

Specialized peripheral receptors• Certain peripheral receptors,

specialized to receive particular stimuli, include mechanoreceptors, thermoreceptor, and nociceptors

• The dendritic ending located in various regions of the body, including muscles, tendons, skin, fascia and joint capsules

continued

• These receptors are classified into three types :– Mechanoreceptors, which respond to

touch– Thermoreceptors,which respond to cold

and warmth– Nociceptors, which respond to pain due

to mechanical stress, extremes temperature differences and chemical substance

Mechanoreceptors

• Mechanoreceptors respond to mechanical stimuli that may deform the receptor or the tissue surrounding the receptor.

• Stimuli that trigger the mechanoreceptors are touch, stretch, vibration and pressure

Nonencapsulated mechanoreceptors

• Are simple unmyelinated receptors present in the skin, connective tissues and surrounding hair follicle– Peritricial nerve ending, located in the

epidermis of the skin, especially in the face and cornea of the eye

– Merckel’s disks, specialized for perceiving discriminatory touch, located in non hairy skin and regions of the body more sensitive to touch.

Encapsulated mechanoreceptors• Encapsulated Mechanoreceptors exhibit characteristic

structure and are present in specific location– 1. Meissner’ corpuscles :

• Specialist for tactile• Location : dermal papillae of the non hair portin

of the hand, eyelids, lip, tongue, nipples, skin of the foot and forearm.

• Each corpuscle is formed by three or four nerve terminals and their associated Schwann cells, all which are encapsulated by connective tissue.

continued

– 2. Pacinian corpuscles• Location : in the dermis and hypodermis in the

digits of the hand, breast, connective tissue of the joint, periosteum and the mesentery

• Spezialied to perceive pressure, touch and fibration

• Morphology : – ovoid & large receptor– Single unmyelinated fiber as a core and its

Schwann cell– Surrounded by approximately 60 layers of

modified fibroblast– Each layer separated by a small fluid-filled

space

Ruffini’s corpuscles• Location : in the dermis of skin, nail

beds, periodontal ligament and joint capsules

• Composition : – branched nonmyelinated terminals

interspersed with collagen fibers – Surrounded by four to five layers of

modified fibroblast

Krause’s end bulb• Morphology :

– Spheris– Unmyelinated nerve ending

• Location : papilla dermis, joints, conjunctiva, peritoneum, genital regions, subendothelial c.t. of the oral and nasal cavities

• Function : unknown, they were thought to be receptors sensitive to cold

Muscle spindles and Golgi tendon organs

• Muscle spindles provide feedback concerning the changes and the rate alteration of the muscle length

• Golgi tendon organs monitor the tension and the rate at which the tension is being produced during movement

• Information from these two sensory structures is processed at the unconscious level within the spinal cord; the information also reaches the cerebellum & cerebral cortex, so that individual may sense muscle position.

Thermoreceptor• Which respons to temperature

differences of about 2° C, are three types: warmth receptors, cold receptors and temperature-sensitive nociceptors.

• Specific receptors have not been identified for warmth

• Cold receptors are derived from naked nerve ending in the epidermis

Nociceptors• Are receptors sensitive to pain caused by

mechanical stress, extreme of temperature, and cytokines as bradykinin, serotonin and histamin.

• Are naked ending of myelinated nerve fibers that branch freely in the dermis before entering the dermis

• Divided into three groups :– Those that respond to mechanical stress or damage– Those that respond to extremes in heat or cold– Those that respond to chemical compound such as

bradykinin, serotonin and histamin

Afferent Endings

Free Nerve Endings - Nerve endings without special structural- Nerve endings without special structural organizationorganization - - pain and temperature receptorreceptor

Expanded Tip Endings - - Merkel’s Touch Corpuscle

Merkel cells in basal layer of epidermisMerkel cells in basal layer of epidermis - Type I Hair cells of Vestibular Labyrinth

Afferent Endings

Encapsulated EndingsEncapsulated Endings - Meissner’s Corpuscle - Pacinian Corpuscle (Corpuscle of Vater-Pacini) - Genital Corpuscle - Ruffini’s Ending - End Bulb of Krause - Golgi tendon organ: Proprioceptor

Receptor

Endings

Ÿ Free nerve ending

Ÿ Expanded tip ending

Ÿ Encapsulated ending

Merkel’s Touch Corpuscle

ŸŸ expanded tip endingexpanded tip ending

Ÿ Merkel cell - clear cell located in the basal layer of epidermis - membrane bound electron dense granules resembles synaptic vesicle

Meissner’s CorpuscleMeissner’s Corpuscle

Pacinian CorpusclePacinian Corpuscle

Efferent EndingsEfferent EndingsSomatic Efferent EndingsSomatic Efferent Endings Neuromuscular JunctionNeuromuscular Junction (Myoneural Junction, Motor End (Myoneural Junction, Motor End Plate)Plate)

Autonomic Efferent Autonomic Efferent EndingsEndings Endings on smooth muscle Endings on smooth muscle

and blood vessels and blood vessels

NeuromuscularNeuromuscularJunctionJunction

(Myoneural Junction,Motor End Plate)

NMJNMJ

MM

NN

Autonomic Efferent EndingsAutonomic Efferent Endings

Neuromuscular SpindleNeuromuscular Spindle• Both receptor and effector• Structure 1. Capsule 2. Intrafusal Muscle Fibers - Nuclear Bag Fiber - Nuclear Chain Fiber

3. Receptor and Effector Nerve 3. Receptor and Effector Nerve

EndingsEndings - Afferent Ending - Efferent Ending

NB: nuclear bag fiber IF: intrafusal muscle fiber

CA: capsule EF: extrafusal muscle fiber