Histology of nervous system

NERVOUS TISSUEDr. Ashfaqur Rahman

MBBS, M.Phil (Anatomy)Associate Professor and Head, Anatomy

Monno Medical College

INTRODUCTION

NEUROANATOMY: THE STUDY OF THE NERVOUS SYSTEM.

2 body systems control all the functions of the body-1. Nervous system- which works very rapidly2. Endocrine system- which works more or less slowly.

Nervous system is also called ‘master system of the body’.

Functions of the nervous system:

1. Reception of sensory stimuli2. Integration of sensory information3. Coordination and control of motor activities4. Assimilation and storage of experiences5. Programming of basic instincts

Sensory stimuli Correlation Effectors

Memory

Classification of nervous systemAnatomically:Central nervous system (CNS)-Brain and spinal cordFunctions:1. Integration, processing and

coordination of sensory data2. Giving appropriate motor commands3. The seat for higher functionsPeripheral nervous system (PNS)-peripheral nerves and associated gangliaFunctions:4. Provides sensory information to CNS5. Carries motor commands of CNS to

the effectors

Functionally/physiologically:1. Somatic nervous system (SNS)2. Autonomic nervous system (ANS)

CELLULAR ORGANIZATIONThe tissue forming the nervous system is called nervous tissue, which is one of the 4 basic tissues of the body. Essentially nervous tissue is a cellular type of tissue, composed of 2 types of cells without ICM.

Composition:1. Neurons/nerve cells-Excitable, non-dividing cell2. Neuroglia/glial cells-Non-excitable, dividable cell

Neuroglia are 10 times more in number than neurons. Blood vessels are also found within nervous tissue which provide nutrition to the neurons and neuroglia.

Organization of grey and white matter- 1. Primitive organization-inner grey matter, outer white

matter- e.g. Brain stem and spinal cord.2. Modified organization-outer grey matter, inner white

matter- e.g. Cerebrum and cerebellum.

Types of the nervous tissue:

Grey matter- The nervous tissue which appears Grey. It is grey due to rich blood supply and absence of myelin. It has rich blood supply because it contains cell bodies of the neuron.Composition: 1. Cell bodies of neurons2. Dendrites and proximal/initial (non-myelinated) portion of

axons, sometimes whole axons (also non-myelinated) 3. Supporting cells-neuroglia (Protoplasmic astrocyte,

perineuronal oligodendrocyte, microglia)4. Blood vessels (abundant)

White matter- The nervous tissue which appears white. It is white due to presence of myelin and less blood supply. It has less blood supply because it does not contain cell bodies of the neuron.Composition: 1. Distal myelinated portion of axons2. Supporting cells-neuroglia (fibrous astrocyte,

intrafascicular oligodendrocyte, microglia)3. Blood vessels (few) (supplying the neuroglia present in

the white matter)

Neuron-Structural & functional unit of nervous systemNeuron doctrine: by Ramon y Cajal- 6 tenets in 1 sentenceNeuron is the anatomical, genetic, functional, polarized, pathologic and regenerative unit of nervous system.

2 parts of neuron-1. Cell body/soma/perikaryon2. Process/neurite

2 types of neurite-3. Axon4. DendriteAxon (& dendrite) is called nerve fiber.

Collection of neuron (cell body) inside CNS is called NUCLEUS.Collection of neuron (cell body) outside CNS is called GANGLION. Collection of nerve fiber inside CNS (specially within spinal cord) is called TRACT.Collection of nerve fiber outside CNS is called NERVE (PERIPHERAL NERVE).

Classification of neurons:According to polarity (number of neurites)/morphological classification:

• Unipolar (pseudounipolar) neurons- Functionally sensory neurons. E.g. Neurons of DRG, neurons of sensory cranial ganglia, neurons of mesencephalic nucleus of trigeminal nerve.

• Bipolar neurons- Functionally sensory neurons. E.g. Bipolar neurons of retina, olfactory cells, neurons of vestibular (Scarpa’s ganglion) and cochlear (spiral) ganglion.

• Multipolar neurons- Functionally motor neurons. E.g. Anterior horn cells of spinal cord, pyramidal cells of cerebral cortex, Purkinje cells of cerebellar cortex, interneurons, neurons of autonomic ganglia. Most of the neurons of CNS are multipolar type.

Classification of neurons:

According to function:

Motor/effector neurons- E.g. Anterior horn cells of spinal cord, pyramidal cells of cerebral cortex, Purkinje cells of cerebellar cortex, neurons of autonomic ganglia.• UMN • LMN• Preganglionic• Post ganglionic

Sensory/receptor neurons- E.g. Neurons of DRG, neurons of sensory cranial ganglia, neurons of mesencephalic nucleus of trigeminal nerve, bipolar neurons of retina, olfactory cells, neurons of vestibular (Scarpa’s ganglion) and cochlear (spiral) ganglion.• Primary• Secondary• Tertiary

Interneurons/internuncial/intercalated/central/associational/connector neurons. >99.9% neurons are of this type. E.g. Column cells of spinal cord.

Classification of neurons:

According to length of neurites (axons)/according to size of neuron:

Golgi type I neurons- E.g. Anterior horn cells of spinal cord, pyramidal cells of cerebral cortex, Purkinje cells of cerebellar cortex. They act as relay neurons.

Golgi type II neurons (microneurons)- E.g. Granule cells and stellate cells of cerebellar cortex, interneurons. They act as associational/interneurons.

Classification of neurons:

Other types:1. Amacrine neurons2. Microneurons (7µM)3. Paraneurons (apolar neurons)

Locations of neurons (cell bodies):1. Within gray matter of CNS2. Within white matter of CNS as nuclei3. Within peripheral ganglia4. Within olfactory epithelium, retina

Development of neurons:1. CNS neurons- from neural tube2. Neurons of peripheral ganglia- from neural crest and

ectodermal placodes

Structure of a neuron:Cell body • Nissle body

(substance/granules)/tigroid or chromodial substance

• Neurofibrils• Centrosome• Axon hillockDendrites• Dendritic spine/gemmulesAxon• Parts

• Preaxon/initial segment• Axon proper• Axon terminale (terminal part)

• Telodendria• Terminal boutons/synaptic

knob• Axolemma• AxoplasmEndoneuriumPerineuriumEpineurium

Difference between axon and dendrite

Neurolemma/neurolemma sheath/sheath of SchwannSchimidt-Lantermann incisura/fissure and segment

Nerve fibers

Axons (and dendrites) of neurons are called nerve fibers.

Classification:According to presence of myelin sheath:1. Myelinated nerve fibers2. Unmyelinated nerve fibers- unmyelinated peripheral

nerves are known as fibers of Remak

According to functions:1. Motor (efferent) nerve fibers2. Sensory (afferent) nerve fibers

Periphery

Nerve fibers

Fiber type

Sub type

CV m/s

Diameter m

Function Myelin

A 70-120 12-20 Motor (extra-fugal fibers of skeletal muscle)

+

40-70 5-12 Sensory (touch, pressure, vibration) +

10-50 3-6 Motor (intra-fugal fibers of skeletal muscle)

+

6-30 2-5 Sensory (temperature, pain-sharp & localized)

+

B 3-15 <3 Motor (preganglionic autonomic fiber) +

C 0.5-2.0 0.4-1.2 Motor (postganglionic autonomic fiber)Sensory (temperature, pain-diffuse & deep)

_

Combined classification:

Receptors (SENSORY)

Biological transducers responsible for reception of any sensory stimulation and conversion of this stimulation into nerve impulse to be carried by nerve fibers are called receptors.

Receptors are sensory nerve endings specialized for reception of stimuli and transforming them in the form of nerve impulses (ref. Vishram Singh).

Classification:

• According to location- Exteroceptors (cutaneous receptors)-from superficial

structures like skin, superficial fascia Interoceptors-from viscera and blood vessels Proprioceptors-from muscle and joint

• Functional classification- Mechanoreceptors Thermoreceptors Nociceptors Chemoreceptors Electromagnatic receptors

• Anatomical classification-

Uncapsulated receptors

Free nerve ending Epidermis, cornea, gut, dermis, fascia, tendon, ligaments, joint capsules, bone, periosteum, perichondrium, dental pulp, tympanic membrane, muscle

Pain, temperature, touch (crude), pressure

Tactile discs of Merkel/Merkel’s disc

Thick (hairless) skin-epidermis Touch and pressure

Hair follicle receptor/Peritrichial plexus

Thin (hairy) skin-dermis Touch

Encapsulated receptors

Meissner’s tactile corpuscle

Dermis of thick (hairless) skin, external genitalia, nipple

Touch (2 point TD)

Pacinian corpuscle Dermis, S/C tissue, joint capsules, ligaments, peritoneum, pleura, external genitalia, nipple

Vibration and pressure

Ruffini’s corpuscle Dermis of thin (hairy) skin Stretch

End bulbs of Golgi-Mazzoni

Genital skin

End bulbs of Krause Mucocutaneous junctions, conjunctiva Temperature (cold)

Neuromuscular spindles Skeletal muscle Stretch-muscle length

Golgi tendon organ Tendons Compression-muscle length

Cutaneous receptorsSensory modalities Type of receptors

Pain, touch and temperature

Free nerve endings

Merkel’s discs

Peritrichial plexus

Pressure and vibration Meissner’s corpuscles

Pacinian corpuscles

Deep pressure Ruffini’s corpuscles

Free nerve endings

Ruffini’s corpuscles

Pacinian corpuscles

Golgi tendon organ

Joint receptors

Neuroglia/Glial cells

• The non-excitable, cellular supporting element of NS is called neuroglia.

• They represent connective tissue of nervous system. They are 5-10 times more numerous than neurons.

• Neuroglia (except microglia), like neurons, develop from neuroectoderm.

• But the basic difference is that neuroglia are capable of division by mitosis whereas neurons are not.

Macroglia Microglia

Astrocyte Oligodendrocyte/oligodendroglia

Ependymal cell

Perineuronal/satellite

Intrafascicular

Resting microglia Gitter cell

Choroidal Epithelial cell

TanycyteEpendymocyteProtoplasmicFibrous

A. Neuroglia of CNS (central neuroglia):

Classification:

B. Neuroglia of PNS (peripheral neuroglia):(some authors regard supporting cells of PNS are not

neuroglia. They regard supporting cells of CNS as neuroglia)-

• Schwann cell/neurolemmal cell/neurolemmocyte• Capsular cell/satellite cell/perineuronal cell/ganglionic

gliocyte/amphicyte

• Others: Pituicyte, Bergman glial cell, Muller cell

Astrocyte• Most numerous glial cell• Star shaped (stellate) body with numerous

radiating process

Astrocyte• Cell body and process contain intermediate

filament, named GFAP (gliofibrils)• Source of development- Neuroectoderm (neural

tube)

• Perivascular feet, forms BBB• Outer glial limiting membrane, forms pia-glial

membrane• Inner glial limiting membrane, forms ependyma-

glial membrane

• Fibrous astrocyte- found in white matter, each process is long, slender, smooth, not much branched. Number of filament numerous.

• Protoplasmic astrocyte- found in gray matter, each process is shorter, thicker, more branched. Number of filament fewer.

Functions of astrocytes• Structural support-for nerve cell bodies and fibers• Act as a scaffolding for migration of young nerve

cell during IUL

• Act as electrical insulator by covering synapse• Form barrier for spread of neurotransmitter• Absorb neurotransmitters and limit actions• Take up excess K+ from ECF• Form BBB• Store glycogen and help in nutrition of nerve cells• Phagocytosis• Replacement gliosis• Secrete trophic substances for neurons

Blood brain barrier

The composite barrier that exist between blood in the vessel and neurons of brain is called blood brain barrier.

Composition:1. Nonfenestrated capillary endothelium and tight junctions

between them.2. Continuous basement membrane of capillary

endothelium.3. Perivascular foot process (and cell bodies) of astrocytes.

Functions:1. Protection of brain from circulating harmful

substances of blood.2. Selective transport of substances from blood by

specialized transport system.

Blood brain barrier

The barrier is absent in:Median eminence of hypothalamusPosterior pituitaryPineal body Area postremaOVLTIntercolumnar tubercleSubfornical organChoroid plexus

Oligodendrocyte (oligodendroglia)• Small cell body with few delicate process (hence

oligodendro)• No intermediate and other filaments• Location:

1. gray matter around nerve cell bodies as satellite cell 2. white matter in rows along myelinated nerve fiber

• Source of development- Neuroectoderm (neural tube)

Functions of oligodendrocyte• Intrafascicular/perifascicular oligodendrocyte- Formation

and maintenance of myelin sheath (medullary sheath) around nerve fibers in CNS

• Perineuronal satellite oligodendrocyte- Surround nerve cell bodies and influence biochemical environment of neuron.

Microglia• Smallest of all neuroglia• They are part of MPS• Small cell body with wavy branching process that give off

numerous spine-like projections• Possess amoeboid movement when activated.• Location: gray and white matter• Source of development- macrophage (mesenchyme).

They migrate to CNS during fetal life.

Functions of microglia• Normally they are inactive- resting microglia• Enlarge and proliferate in disease condition- Gitter cell-

help in phagocytosis, act as scavenger cells of CNS, act as APC

Ependymal cell• Source of development- Neuroectoderm (neural

tube).• Have no basal lamina.

1. Ependymocyte- cuboidal or low columnar shaped cell, with cilia and microvilli, line ventricles of brain and central canal of spinal cord.

2. Tanycyte- line floor of the 3rd ventricle overlying median eminence of hypothalamus, possess long basal processes.

3. Choroidal epithelial cell- cover surfaces of choroid plexus. Form blood-CSF barrier.

Functions of ependymal cell1. Ependymocyte- Help in circulation of CSF by ciliary

beat. Absorb CSF by microvilli.2. Tanycyte- Transport chemical substances from CSF

to hypophyseal portal system and play a part in control of hormone production by anterior pituitary.

3. Choroidal epithelial cell- Production and secretion CSF from choroid plexus.

Blood CSF barrier

The composite barrier that exist between blood in choroid capillary and CSF within ventricles of brain is called blood CSF barrier. It is a weaker barrier than blood brain barrier.

Composition:1. Fenestrated capillary endothelium.2. Continuous basement membrane of capillary endothelium.3. Pale cell layer.4. Continuous basement membrane of choroidal epithelial

cell.5. Choroidal epithelial cell and tight junctions (performing

actual barrier function) between them.

Functions:1. Protection of brain from circulating harmful

substances of blood.2. Selective transport of substances from blood by

specialized transport system

E

A

A

A

O

O A

M

Schwann Cells (Neurolemmocytes)

Derived from the neural crest.

Found only in the PNS

Responsible for myelination in PNS

One Schwann cell forms myelin around a segment of one axon, in contrast to the ability of oligodendrocytes to branch and sheath parts of more than one axon.

Satellite Cells of Ganglia/Ganglionic Gliocytes

Derived from the neural crest.

Form a covering layer over the large neuronal cell bodies in PNS ganglia.

The satellite cells exert a trophic or supportive role, but the molecular basis of their support is poorly understood.

Synapse Specialized areas of contacts between two or more

neurons. Now-a days neuromuscular junctions are also called synapse.

Classification of synapse-1. Chemical synapse2. Electrical synapse

Chemical synapseSynapse where transmission of impulse occurs through chemical substances called neurotransmitters.Structure of chemical

synapse-• Presynaptic neuron• Presynaptic

(synaptic/terminal) knob (bouton terminale/end feet)

• Presynaptic (transmitter) vesicle (synaptosome)

• Presynaptic membrane, presynaptic density, release site, voltage gated Ca ++ channel

• Postsynaptic membrane, postsynaptic density (synaptic or subsynaptic web)

• Synaptic cleft (neuropil area) 20nm

• Synaptic delay (0.5msec)• Enzymes• Neurotransmitters-

excitatory/inhibitory• Receptors-

excitatory/inhibitory• Parts of a receptor protein-

• binding component• ionophore component• 2 types-

1. ion channel- cation channel/anion channel

2. 2nd messenger activator • EPSP/IPSP

Types-

Structurally and functionally-

1. Asymmetrical/type 1/excitatory synapse

2. Symmetrical/type 2/inhibitory synapse

According to synapsing structures-

1. Axodendritic- 80-95%

2. Axosomatic- 5-20%3. Axoaxonic4. Dendrodendritic5. Somatodendritic6. Somatosomatic

1. Small molecule, rapidly acting transmitters Class I

Acetylcholine- Both excitatory and inhibitory

Class II: The Amines Norepinephrine- Both excitatory and

inhibitory Epinephrine- Both excitatory and

inhibitory Dopamine- Both excitatory and

inhibitory Histamine Serotonin- Inhibitory

Class III: Amino acids GABA- Inhibitory Glycine- Inhibitory Glutamate- Excitatory Aspartate- Excitatory

Class IV NO

2. Large molecule, slowly acting transmitters (Neuropeptides)

• Principal neurotransmittersAcetylcholine

(nicotinic)GlutamateGABA

• NeuromodulatorsAcetylcholine

(muscarinic)SerotoninHistamineAdenosine Neuropeptides

Neurotransmitters/NeuromediatorsChemical substances secreted by presynaptic neuron at synaptic cleft of chemical synapse which transmit nerve impulse to the post synaptic neuron. Classification-

Structure of autonomic ganglion

Connective tissue capsule

Cell bodies of post ganglionic neurons

Interneurons – SIF cells

Satellite/capsular cells

Nerve fibers-Pre- and postganglionic fibers

and fibers traversing the ganglion without synapse

GanglionCollection of (cell bodies of) neuron outside CNS is

called ganglion.

Structure:• Ovoid in shape • Contain collection of cell bodies of neurons-

(pseudo)unipolar or bipolar in case of sensory ganglion, multipolar in case of motor ganglion.

• Each cell body is covered by a layer of capsular/satellite cells.

• Each ganglion is covered by a connective tissue capsule.

Classification

Sensory ganglion (Somatic ganglion)• Cranial ganglion

• Trigeminal ganglion of C5• Geniculate ganglion of C7• Vestibular and spiral ganglion of C8• Superior and inferior ganglion of C9• Superior and inferior ganglion of C10

• Spinal ganglion• Dorsal root ganglion

Motor ganglion (Autonomic ganglion)Sympathetic ganglion• Lateral (paravertebral) ganglia- Ganglionated

sympathetic trunk• Subsidiary ganglia

• Collateral (prevertebral) ganglia• Superior mesenteric ganglion• Inferior mesenteric ganglion• Aorticorenal ganglion (renal)• Superior hypogastric ganglion

• Terminal ganglia- Adrenal medulla

Motor ganglion (Autonomic ganglion)Parasympathetic ganglion• Collateral ganglia (cranial parasympathetic

ganglia)• Ciliary ganglion• Pterygopalatine ganglion• Submandibular ganglion• Otic ganglion

• Terminal ganglia- close to or within wall of viscera

• Ganglia of cardiac plexus• Ganglia of pulmonary plexus• Ganglia of myenteric plexus• Ganglia of submucosal plexus• Inferior hypogastric ganglion

Myelination

CNS-By OligodendrocyteOf spinal cord-at 4th month of IUL, sensory fibers firstOf brain-at 6th month of IUL, motor fibers first

PNS-By Schwann cell

Structure of a myelinated nerve fiberOf CNS-

AxonMyelin sheath

Of PNS-AxonMyelin sheathNeurilemmaBasement membraneEndoneurium