Histology Lecture 7 & 8

Front 1

What are the general functions of the nervous system?

Back 1

1) Responds to changes in internal/external environment
2) Regulates organ activities

Front 2

What are the anatomical divisions of the nervous system?

Back 2

1) CNS- brain and spinal cord
2) PNS- nerves (cranial, spinal, and peripheral) that transmit info to/from CNS

Front 3

Describe an afferent nerve

Back 3

Travels toward CNS

Front 4

Describe an efferent nerve

Back 4

Travels away from CNS

Front 5

What are the functional divisions of the nervous system?

Back 5

1) Somatic nervous system (SNS)- provides sensory and motor innervation to all parts of body except viscera, smooth muscle, and glands
2) Autonomic nervous system (ANS)- efferent involuntary motor innervation to smooth muscle, the conducting system of heart and glands; afferent sensory innervation from viscera (pain and autonomic reflexes); further subdivisons of ANS- sympathethic, parasympathetic, and enteric

Front 6

Describe the development of the nervous system

Back 6

1) Ectoderm germ layer--> neural crest and neural plate
2) Neural plate grows in response to signals from notochord--> invaginates--> neural groove--> closes to form neural tube--> CNS structures
3) Neural crest separates from neural tube and ectoderm--> PNS neurons and glial cells, arachnoid, and pia mater

Front 7

What is a neuron?

Back 7

Structural and functional unit of nervous sytem

Front 8

What are 4 characteristics of a neuron?

Back 8

1) Function- receives and transmits info as electrical impulses
2) Synapses- site of interaction/contact between neurons and/or target cells
3) DO NOT DIVIDE (multipotent precursor cells in ventricular zone CAN generate new neurons--> migrate to site of injury and differentiate into new neurons
4) Derived from: CNS- neural tube, PNS- neural crest cells

Front 9

What are the 3 functional units of the neuron?

Back 9

1) Cell body
2) Axon
3) Dendrite

Front 10

Describe the cell body

Back 10

1) LM appearance: large, euchromatic nucleus w/ prominent nucleolus (distinguishing feature); rER (nissl bodies), mitochondria, golgi, lysosomes (with lipofuscin), microtubules (transport), neurofilaments (equivalent to intermediate filaments), and vesicles
2) Organelles (nissl bodies and free ribosomes) extend into dendrites but NOT into axon
3) Axon hillock- region of cell body free of LARGE cytoplasmic organelles, site of origin of axon

Front 11

Describe the axon

Back 11

1) Largest process extending form cell; originates from axon hillock, may give rise to recurrent brand near cell body
2) Transmits impulses AWAY from cell body to target cell
3) Contains microtubules, neurofilaments, mitochondria, and vesicles
4) Initial segment- region of axon between apex of axon hillock and beginning of myelin sheath (site of generation of action potential)
5) Periaxoplasmic plaque- site of protein synthesis in large nerve terminals

Front 12

Describe the dendrite

Back 12

1) Usually many per neuron
2) Shorter process with greater diameter than axon
3) Receives and transmits info TOWARD cell body
4) UNMYELINATED and can form extensive aborborizations called dendritic trees; used to characterize neuron types (pyramidal or Purkinje cells)
5) Does NOT contain Golgi

Front 13

What are the 3 morphological characterizations of neurons?

Back 13

1) Multipolar
2) Bipolar
3) Pseudounipolar (unipolar)

Front 14

Describe a multipolar neuron

Back 14

1 axon and 2 or more dendrites
Most abundant
Includes motor, interneurons, pyramidal cells of cerebral cortex, Purkinje cells of cerebellar cortex

Front 15

Describe a bipolar neuron

Back 15

1 axon and 1 dendrite
Sensory
Located in olfactory bulb, vestibular and auditory

Front 16

Describe a pseudounipolar neuron

Back 16

1 process (axon) divides into 2 long processes
Majority located in dorsal root ganglia and cranial nerve ganglia

Front 17

Describe the functional classifications of a neuron

Back 17

1) Sensory
2) Motor
3) Interneurons

Front 18

Describe sensory neurons

Back 18

Pseudounipolar (unipolar)
Afferent- carry impulses from receptors to CNS
Cell body in DRG; 1 axon branch extends to periphery and other extends to CNS
Somatic afferent fibers- pain, temperature, touch and pressure from body surface; pain and proprioception from organs; visceral afferent fibers- pain and other sensations from mucous membranes, glands, and blood vessels

Front 19

Describe motor neurons

Back 19

Multipolar
Efferent- convey impulses from CNS or ganglia to effector cells
Somatic efferent- impulses to skeletal muscles; visceral efferent muscles- involuntary impulses to smooth muscle, cardiac conducting cells (Purkinje fibers) and glands

Front 20

Describe interneurons

Back 20

Multipolar or intercalated
Neurons whose axons do not ramify outside its local area
Forms network between neurons

Front 21

Describe the axonal transport systems

Back 21

Bidirectional transport (via microtubules) of material between cell bodies and axons and dendrites; described by direction of travel: anterograde or retrograde

Front 22

Describe anterograde transport

Back 22

Cell body to periphery via kinesin

Front 23

Describe retrograde transport

Back 23

Periphery to cell body via cytoplasmic dynein

Front 24

What are the two types of transport based on rate of transport?

Back 24

1) Slow transport system
2) Fast transport system

Front 25

Describe the slow transport system

Back 25

0.2-4mm per day
Only in anterograde direction
Carries structural elements (neurofilaments and microtubules) and cytoplasmic matrix proteins

Front 26

What are the two types of fast transport?

Back 26

1) Fast anterograde
2) Fast retrograde

Front 27

Describe fast anterograde transport

Back 27

20-400 mm per day
Membrane-limited organelles and low molecular weight materials

Front 28

Describe fast retrograde transport

Back 28

20-400 mm per day
Same molecules as fast anterograde and endocytosed materials
Utilized by toxins and viruses that enter CNS at nerve endings

Front 29

Describe the method of infection of Rabies

Back 29

1) Axonal transport in pathogenesis of neurologic infectious diseases
2) Bite from rabies-infected animal releases virus into muscle--> replicates
3) Virus is released from infected muscle and binds ACh receptor of innervating neuron
4) Virus carried by fast retrograde transport to neuronal cell body and ultimately to CNS--> replicates and causes encephalitis (clinical stage)
5) In peripheral nerve innervating salivary glands utilizes anterograde transport to infect new victim--> virus transferred by saliva by bite
6) Negri and lyssa bodies- eosinophilic cytoplasmic inclusions

Front 30

Describe a synapse

Back 30

1) Site of transmission of impulse between neurons and target cells
2) LM appearance: visualized by silver precipitation staining methods (golgi)- appears as oval bodies on surface of receptor neuron
3) Boutons en passant- multiple synapses generated by travel of incoming neuron along surface of target
4) Bouton terminal or end bulb- enlarged tip at end of axon
5) Variation in number of synapses appears directly related to number of impulses neuron is receiving and processing

Front 31

What are the 3 morphologic classifications of synapses?

Back 31

1) Axodendritic- between axon and dendrite
2) Axosomatic- between axon and cell body
3) Axoaxonic- between axon and axon

Front 32

What are the two classifications of synapses based on mechanism of conduction?

Back 32

1) Chemical synapse- uses release of chemical (neurotransmitter)
2) Electrical synapse- uses ion tranfer between cells via gap junction

Front 33

Describe the electrical synapse

Back 33

1) Direct spread of electrical current between cells
2) Does not require neurotransmitters for function
3) Mammalial equivalents: gap junctions in smooth and cardiac muscle cells

Front 34

What are the three components of the typical chemical synapse?

Back 34

1) Presynaptic knob- end of neuronal process; site of storage and release of synaptic; contains mitochondria and presynaptic density (proteins)
2) Synaptic cleft- 20-30 nm space between pre- and post-synaptic clefts
3) Postsynaptic membrane- receptor sites for neurotransmitters--> postsynaptic density

Front 35

Describe 5 characteristics of acetylcholine (ACh)

Back 35

1) Neurotransmitter between axons and striated muscle at neuromuscular junction
2) Neurotransmitter in ANS, released by preganglionic sympathetic and parasympathetic neurons; post-synaptic parasympathetic neurons
3) Neurons that use ACh as neurotransmitter are called cholinergic neurons
4) ACh receptor called cholinergic receptors- muscarinic and nicotenic ACh receptors
5) Drugs affect release of ACh and its interaction with receptor

Front 36

Describe botulinum toxin (botulism)

Back 36

Inhibits ACh release--> decrease receptor stimulation--> paralysis of skeletal muscle and respiratory distress

Front 37

What are three catecholamines?

Back 37

1) Norepinephrine
2) Epinephrine
3) Dopamine

Front 38

What are catecholamines synthesized from?

Back 38

Amino acid tyrosine

Front 39

What is norepinephrine a transmitter for?

Back 39

Between post-synpatic sympathetic axons and effectors in ANS
Exception is sweat glands and some blood vessels innervated by cholinergic (ACh) sympathetic system

Front 40

What is an adrenergic neuron?

Back 40

Neurons using norepinephrine as a neurotransmitter

Front 41

What secretes epinephrine?

Back 41

Some cells in CNS and endocrine cells (chromaffin cells) of adrenal medulla during fight or flight response

Front 42

Describe dopamine

Back 42

Stimulates motor neurons
Absence of dopamine motor neurons--> unable to control movement and cooridination

Front 43

Describe Parkinson's disease

Back 43

1) Second most common neurodegenerative disease
2) Loss of dopaminergic neurons in substantia nigra and basal ganglia of brain (~80% lost by time symptoms appear)
3) Loss of pigmentation, increase in number of glial cells, presence of Lewy bodies
4) ~20% have family members with similar symptoms; symptoms may also result from environment- infections (encephalitis), toxins, neuroleptics, repetitive trauma

Front 44

What are the symptoms associated with Parkinson's disease?

Back 44

1) Resting limb tremors, especially hand
2) Rigidity or increased stiffness in all muscles
3) Bradykinesia (slow movements)
4) Akinesia (inability to start movements)
5) Lack of spontaneous movements
6) Loss of postural reflexes
7) Slurred speech

Front 45

What is the treatment for Parkinson's?

Back 45

1) Relieving symptoms
2) L-Dopa- precursor of dopa that crosses blood-brain barrier
3) Cholinergic receptor blockers
4) Amantadine (stimulates release of DA from neurons)
5) Transplantation of dopaminergic neurons (aborted fetus)--> ethical considerations and fetal tissue developed disease
6) Surgery to remove overactive regions of brain (thalamus)
7) Electrodes implanted into brain to destroy thalamus and/or block brain waves that cause uncontrollable movement

Front 46

Describe serotonin (or 5-hydroxytryptamine, 5-HT)

Back 46

1) Formed by tryptophan
2) Neurotransmitters in neurons of CNS and enteric nervous system
3) Neurons that use- serotonergic
4) Portion of serotonin is recycled by reuptake into presynaptic serotonergic neurons

Front 47

What amino acids function mainly in the CNS?

Back 47

1) y-aminobutyrate (GABA)
2) Glutamate (GLU)
3) Glycine (GLY)

Front 48

What are the main neurotransmitters of the CNS?

Back 48

y-aminobutyrate (GABA) and glutamate (GLU)

Front 49

Describe small peptides

Back 49

1) Substance P, hypothalmic releasing hormones, enkephalins, vasoactive intestinal peptide (VIP), cholecytokinin (CCK), and neurotensin
2) Many are synthesized and released by enteroendocrine cells of intestinal tract
3) Also synthesized and released by endocrine organs and by neurosecretory neurons of hypothalamus

Front 50

Describe the simple gas, nitric oxide

Back 50

1) Carries impulse from one neuron to another
2) Synthesized within synapse and used immediately (GLU activates NO synthase--> NO)

Front 51

What are the two types of neurotransmitter synapse?

Back 51

1) Excitatory
2) Inhibitory

Front 52

Describe the excitatory synapse

Back 52

1) Initiates action potential
2) Cation channels open--> influx of Na+--> local depolarization of post-synaptic membrane
3) Neurotransmitters- acetylcholine, glutamate, or serotonin

Front 53

Describe the inhibitory synapse

Back 53

1) More difficult to generate action potential
2) Anion channels open--> influx of Cl- into cell--> hyperpolarizes post-synaptic membrane (becomes more negative)
3) Neurotransmitters include: y-aminobutyric acid (GABA) or glycine

Front 54

Describe the membrane potential

Back 54

1) Difference in electrical potential across the cell membrane
2) K+ leaks out of the cell but the intracellular concentration of K+ is maintained by the Na+/K+ pump, which actively exchanges 3 Na+ for 2 K+ ions
2) This means high extracellular Na+ concentration and high intracellular K+ concentration
3) Resting membrane potential occurs when there is no net movement of K+ ions. Results in potential difference of ~70mV across membrane with respect to outside of cell

Front 55

Describe the synaptic transmission (chemical synapse)

Back 55

1) Membrane depolarization opens voltage-gated Ca2+ channels
2) Influx of Ca2+ --> fusion of synaptic vesicles with pre-synaptic membrane and quantal release of neurotransmitters into synaptic cleft via exocytosis
3) Neurotransmitters diffuse across cleft and bind receptor on post-synaptic membrane --> opening ligand-gated Na+ channel --> Na+ enters post-synaptic membrane
4) Depolarization --> open voltage-gated Na+ channels and generate an action potential (briefly reverses potential of resting membrane (-70mV) to positive (+30mV))
5) Na+ channels close and voltage-gated K+ channels open --> K+ leaves axon --> membrane returns to resting potential (-70 mV)
6) Membrane depolarization sends electrical current to neighboring unstimulated membrane repeating depolarization along membrane
7) Firing of impulses in post-synaptic membrane due to summation of hundreds of synapses (both excitatory and inhibitory; other neurons not directly involved in a synapse can impact impulse transmission)

Front 56

Describe the removal of neurotransmitters from the synaptic cleft

Back 56

1) Limits duration of stimulation/inhibiton of post synaptic membrane
2) 80% of released neurotransmitters undergo high-affinity reuptake via transporters into vesicles in pre-synaptic knob
3) Enzymes associated with post-synaptic membrane degrade remaining 20% of neurotransmitters (acetlycholinesterase (AChE) and catechol O-methyltransferase (COMT) and monoamine oxidase (MAO) degrade norepinephrine)

Front 57

What are Schwann cells?

Back 57

Supporting cells of the PNS

Front 58

Describe the development of Schwann cells

Back 58

Develop from neural crest cell
Mostly by mitosis in peripheral nerve

Front 59

What are the functions of Schwann cells?

Back 59

1) Produce myelin sheath- isolates axon and ensures rapid conduction of action potential; 1 cell myelinates 1 axon
2) Support both myelinated and unmyelinated nerve cell fibers
3) Guide regrowth of PNS axons (regeneration and remyelination of severed PNS axons)
4) Clean up PNS debris

Front 60

Describe the myelin sheath

Back 60

1) Lipid-rich layer
2) Does not cover axon hillock or synapses
3) Thickness determined by axon diameter
4) LM appearance: not retained; clear space around axon
5) EM appearance: concentrically arranged, electron dark lamellae (layers) and electron-light spaces around axon
6) Node of Ranvier

Front 61

Describe a Node of Ranvier

Back 61

1) Myelin-free junction between two adjacent Schwann cells
2) Internodal segment- myelin between two sequential nodes
3) External lamina- secreted by Schwann cell, surrounds Schwann cell-axon complex and is continuous across node
4) Saltatory (discontinued) conduction: nerve impulse jumps from node to node allowing faster conduction of impulse
5) Site of voltage reversal- plasma membrane contains high concentration of voltage-gated Na+ and K+ channels exposed to extracellular space

Front 62

Describe satellite cells

Back 62

1) Small cuboidal cells that surround neuronal cell bodies of PNS ganglia
2) LM appearance: only nuclei typically visible in H&E

Front 63

What are four functions of satellite cells?

Back 63

1) Establish and maintain microenvironment around neuronal body in ganglion
2) Electrical insulation
3) Metabolite exchange
4) Does not make myelin

Front 64

Describe enteric glial cells

Back 64

Morphologically and functionally similar to astrocytes in CNS

Front 65

What are the functions of enteric glial cells?

Back 65

Structural, metabolic, protective support of neurons located within ganglia of enteric ANS

Front 66

Describe neuroglia (glial cells)

Back 66

1) Supporting cells of CNS
2) Derived from neural tube
3) More numerous than neurons
4) LM appearance: only nuclei routinely seen; special stain for complete visualization

Front 67

What are the four types of CNS supporting cells?

Back 67

1) Oligodendrocytes
2) Astrocytes
3) Microglia
4) Ependymal cells

Front 68

Describe microglia of the CNS

Back 68

1) Phagocytic cells (originate from monocyte-->vimentin IF); enter CNS from vascular system
2) Account for ~5% of all glial cells in adult CNS
3) Proliferate and become active in areas of injury and disease
4) Smallest of neuroglial cells with small, elongated nuclei (distinguishing feature)
5) Short twisted processes seen with heavy metal staining
6) Both processes and cell body covered with spikes (analogous to ruffled border of other phagocytic cells)
7) EM analysis: lysosomes, inclusions, and vesicles but little rER, microtubules or actin filaments
8) Immune protectors of CNS

Front 69

Describe astrocytes of CNS

Back 69

1) Largest of neuroglial cells- derived from neural tube
2) LM appearance: large, oval, light-staining nucleus (distinguishing feature)
3) Contain prominent bundles of intermediate filaments composed of glial fibrillary acidic protein (GFAP), more numerous in fibrous astrocytes
4) Radial astrocytes- can span entire thickness of brain- provides scaffold for migrating neurons during development
5) Extends processes to blood vessels and neurons

Front 70

What are the functions of astrocytes of the CNS?

Back 70

1) Physical and metabolic support for CNS neurons
2) Movement of metabolites and waste
3) Regulate ionic concentrations
4) Maintain tight junctions of capillaries--> blood brain barrier
5) Covers bare areas of myelinated axons (nodes and synapses)- confines neurotransmitters to synaptic cleft

Front 71

What are two types of astrocytes?

Back 71

1) Protoplasmic astrocytes
2) Fibrous astrocytes

Front 72

What are protoplasmic astrocytes?

Back 72

1) More prevalent in gray matter
2) Numerous short, branching cytoplasmic processes
3) At brain and spinal cord surfaces, extend processes (subpial feet) to basal lamina of pia mater to form glia limitans- relatively impermeable barrier surrounding CNS

Front 73

Describe fibrous astrocytes

Back 73

1) More common in white matter
2) Fewer processes and are relatively straight
3) Fibrous astrocytomas account for ~80% of adult primary brain tumors

Front 74

Describe oligodendrocytes

Back 74

1) Derived from neural tube
2) Produces myelin (concentric layers of oligodendrocyte plasma membrane)
3) Multiple processes of single oligodendrocyte may myelinate one or more nearby axons
4) Nucleus of oligodendrocyte may be at a distance from axons it myelinates
5) LM appearance: small cell with few processes compared to astrocyte; often aligned in rows between axons; irregular, darkly stained nuclei (distinguishing feature)

Front 75

What are three differences between myelin sheaths in the CNS and PNS?

Back 75

1) No external lamina in CNS--> increase contact between myelin of adjacent cells
2) Nodes of Ranvier in CNS are larger therefore more efficient saltatory conduction
3) Unmyelinated neurons in CNS are not embedded in glial cell processes (i.e. no supporting cells around umyelinated axons in CNS)

Front 76

Describe ependymal cells

Back 76

1) Form epithelium-like lining of fluid-filled cavities of CNS (i.e. lines central canal and brain ventricles
2) Single layer of cuboidal to columnar cells (characteristics of fluid-transporting cells- junctional complexes, cilia and microvilli)
3) Lack external lamina; do not have basal infoldings--> interdigitate with astrocyte processes
4) Derived from neural tube

Front 77

Describe the choroid plexus

Back 77

Modified ependymal cells and associated capillaries located within brain ventricles
Produces CSF from uptake of molecules from capillaries

Front 78

Describe the role of CSF

Back 78

Protects and supports brain and spinal cord from external forces and allows removal of metabolic wastes

Front 79

Describe hydrocephalus

Back 79

1) Water on the brain; affects 1 in 500 births
2) Build-up of fluid--> increase pressure--> expansion of skull bones
3) Due to lack of asorption of CSF; block in flow of CSF; overproduction of CSF
4) Causes can be acquired: tumor, infection, prematurity, bleed inside head, birth injury, abnormal blood vessel formation, trauma; or genetic: defect in cilia formation or function
5) Symptoms in infants include: rapid increase in head circumference, vomiting, sleepiness, irritability, downward deviation of eyes and seizures; adults also display headache, gait and cooridination issues, blurred and double vision, progressive mental impairment and dementia
6) Diagnosed by clinical neuroligical evaluation and brain imaging (CT, MRI)
7) Treatment: shunt to remove excess CSF

Front 80

Describe a demyelinating disease of the CNS

Back 80

Characterized by preferential damage to myelin sheath--> decrease or loss of action potential transmission
Example: multiple sclerosis

Front 81

Describe multiple sclerosis

Back 81

1) Demyelination in multiple areas of CNS--> chronic progressive episodes of neurologic deficits: unilateral vision impairments, loss of cutaneous sensation, muscle coordination and movement, bladder/bowel control
2) Increase in IgG in CSF and abnormalities in T cell function (attacks myelin in CNS--> myelin detaches; loss of oligodendrocytes due to T cell-induced apoptosis)
3) Chemical changes in lipid/protein components of myelin--> irregular, multiple plaques--> pathological feature; myelin loss inhibits action potential conduction
4) Treatment: decrease immune response with interferon, adrenal steroids and imunosuppressive drugs

Front 82

Describe the gray matter of the CNS

Back 82

Outer covering or cortex
Contains nerve cell bodies, axons, dendrites, and glial cells

Front 83

Describe the nuclei of the CNS

Back 83

Functionally related groups of nerve cell bodies

Front 84

Describe the white matter of the CNS

Back 84

Contains axons of nerve cells plus associated glial cells and blood vessels

Front 85

What is a tract in the CNS?

Back 85

Bundles of axons going to or coming from specific location

Front 86

Describe pyramidal neurons

Back 86

Cells of gray matter of cerebrum
6 layers or lamina
Modified multipolar neurons
Large triangle-shaped cells with apical and two lateral dendrites

Front 87

What are the three layers of the cerebellar cortex?

Back 87

1) Molecular layer
2) Purkinje cell layer
3) Granule cell layer

Front 88

Describe the molecular layer of the cerebellar cortex

Back 88

Outermost layer
Few neurons
Mostly fibrous (neurophil) from Purkinje and granule cell processes

Front 89

Describe the Purkinje cell layer of the cerebellar cortex

Back 89

Middle layer containing single row of large pear-shaped neurons
Inhibitory output (GABA)

Front 90

Describe the granule cell layer of the cerebellar cortex

Back 90

Innermost layer
Lots of small neurons with dark staining nuclei
Excitatory and inhibitory output

Front 91

Describe the blood-brain barrier

Back 91

1) Restricts transfer of molecules of bloodstream --> CNS
2) Formed early in embryogenesis from interaction between glial astrocytes and capillary endothelial cells- created by tight jxns between endothelial cells eliminating gaps between endothelial cells and preventing diffusion, close association of astrocyte end foot processes with basal lamina of endothelial cells (astrocytes regulate tight junctions)
3) Pinocytosis restricted across brain endothelial cells
4) Molecules cross capillary wall by active transport
5) Astrocyte end feet play important role in maintaining water homeostasis in brain- site of water channels (aquaporin AQP4)--> water crosses blood-brain barrier, important in reestablishment of osmotic equilibrium in brain during edema
6) Barrier inefective or absent in some regions of brain- neurohypophysis (posterior pituitary), circumventricular organs; brain may need to sample blood to regulate neurosecretory control of nervous and endocrine systems

Front 92

Describe the passing of some molecules through the blood-brain barrier

Back 92

1)O2 and CO2 easily cross endothelial cells
2) Glucose (neuron depends almost exclusively for energy), amino acids, nucleosides and vitamins require active transport proteins
3) Other endothelial cell surface proteins prevent crossing of drugs, foreign proteins, etc

Front 93

What are the three layers of CT membranes (meninges) of the brain and spinal cord?

Back 93

1) Pia mater
2) Arachnoid mater
3) Dura mater

Front 94

Describe the dura mater

Back 94

1) Outermost layer, two thick layers of dense CT; periosteal layer- continuous with periosteum of skull and meningeal layer fuses with periosteal
2) Serves as principal channels for blood returning from brain
3) Sheetlike extensions of inner surface form partitions between parts of brain- support brain and carry arachnoid to deeper parts of brain
4) In spinal cord, meningeal layer forms a separate tube surrounding spinal canal
5) Two potential spaces: epidural (site of injection of analgesic drugs) and subdural (between dura and arachnoid, site of blood accumulation)

Front 95

Describe the arachnoid mater

Back 95

1) Delicate CT adjacent to inner surface of dura
2) Extends trabeculae to pia mater
3) Trabeculae composed of loose CT fibers containing elongated fibroblasts
4) Space bridged by trabeculae is subarachnoid space--> contains CSF

Front 96

Describe the pia mater

Back 96

1) Innermost layer; lies directly on brain and spinal cord surface; continous with perivascular CT sheath of blood vessels of brain and spinal cord
2) Delicate CT
3) Fuses with arachnoid around opening for cranial and spinal nerves as they exit dura mater

Front 97

Describe the organization of the spinal cord

Back 97

1) Flattened cylindrical structure directly continuous with brain
2) Divided into 31 segments that are connected to pair of spinal nerves: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral and 1 coccygeal
3) Each spinal nerve joined to its segment of cord by number of roots or rootlets- dorsal (posterior) and ventral (anterior)
4) Cross section appearance: butterfly-shaped gray inner region and white peripheral region

Front 98

Describe the white matter of the spinal cord

Back 98

Contains myelinated and unmyelinated axons

Front 99

Describe the gray matter of the spinal cord

Back 99

Contains neuronal cell bodies, dendrites, axons and neuroglia

Front 100

Describe the anterior (ventral) horn of gray matter

Back 100

1) Site of cell bodies of motor neurons --> innervate striated muscle
2) Ventral motor neurons are multipolar, basophilic cells
3) Motor neurons contain large amounts of yellowish lipofuscin granules
4) Conducts impulses away from CNS- efferent neuron
5) Axon of motor neuron exits spinal cord--> ventral root becomes a component of spinal nerve--> travels to muscle
6) Axon is myelinated except at site of origin and termination
7) Near muscle cell, axon divides into numerous terminal branches--> forms neuromuscular synapses (motor end plates) with muscle cell

Front 101

Describe a peripheral nerve

Back 101

1) Bundle of nerve fibers held together by CT
2) Carry both sensory and motor information
3) Cell bodies may be located within the CNS or outside CNS in peripheral ganglia
4) Ganglia: clusters of neuronal cell bodies that reside outside of CNS and nerve fibers leading to and from it
5) Dorsal root ganglion (DRG): cell bodies of sensory neurons
6) Cell bodies in paravertebral, prevertebral, and terminal ganglia are postganglionic motor neurons (visceral efferents) of ANS

Front 102

Describe somatic efferent motor neurons

Back 102

1) Innervate skeletal muscle
2) Cell bodies lie in brain, brainstem, and spinal cord
3) Axons leave CNS and travel in peripheral nerve to muscle
4) Single neuron conveys impulses from CNS to muscle

Front 103

Describe visceral efferent motor neurons of ANS

Back 103

1) Innervate smooth/cardiac muscle and glands
2) Chain of two neurons connects CNS to effector organ(s)
3) Cell bodies of preganglionic (presynaptic) neurons located in specific region of CNS
4) Axons exit CNS--> travel in peripheral nerve to synapse with postganglionic (postsynaptic) neurons in peripheral ganglia (i.e. at synapse station)

Front 104

Describe somatic and visceral afferent neurons

Back 104

1) Single neuron connects receptor via sensory ganglion to spinal cord or brainstem
2) Cell bodies located in ganglia outside CNS along dorsal roots of spinal nerves (DRG) and in association with cranial nerves V, VII, VIII, IX and X

Front 105

What are the three layers of CT that surround peripheral nerves?

Back 105

1) Endoneurium
2) Perineurium
3) Epineurium

Front 106

Describe the endoneurium

Back 106

1) Bundles nerve fibers into fascicle
2) Type III collagen (Schwann cell derived) surrounds each individual nerve fiber
3) LM appearance: not apparent; requires special stain
4) EM appearance: collagen fibrils run parallel to and around nerve fibers
5) CT cells: few fibroblast (Schwann cells generate collagen fibrils), mast cells
6) 90% nuclei in cross sections of peripheral nerves are Schwann cells; 10% fibroblasts, endothelial cells and mast cells
7) Poorly vascularized- metabolic exchange occurs by diffusion with blood vessels in perineurial sheath

Front 107

Describe the perineurium

Back 107

1) Metabolically active diffusion barrier- contributes to formation of blood-nerve barrier
2) Specialized CT cells surrounding nerve fascicles; formed by one or more layers of squamous cells (perineurial cells) with contractile properties (actin filaments)
3) Perineurial cells express surface receptors, transporters, and enzymes allowing active transport
4) Immune system cells (lymphocytes, plasma cells) not found within endoneurial or perineurial

Front 108

Describe the layers within the perineurium of peripheral nerve

Back 108

1) Collagen fibrils present between layers
2) Each layer has external (basal) lamina on both surfaces
3) No fibroblasts
4) Tight junctions (between cells within same layer)- basis for blood-nerve barrier

Front 109

Describe the epineurium

Back 109

1) Outermost CT of peripheral nerve
2) Dense, irregular CT surrounds and binds nerve fascicles into common bundle
3) Often associated with adipose tissue in larger nerves
4) Contains blood vessels that supply nerve--> branch and penetrate into nerve and travel within perineurium

Front 110

Describe the dorsal root of the spinal nerve

Back 110

1) Site of cell bodies of sensory (pseudounipolar) neurons- afferent (into CNS)
2) Ganglia- collection of neuronal cell bodies outside CNS
3) Large cell bodies arranged as closely packed clusters with alternating layers of neurons and nerve fibers- important histiological features of DRG
4) Nerve impulses are generated in terminal receptor arborization of peripheral segment of nerve

Front 111

Describe the afferent (sensory) receptors

Back 111

1) Specialized structures located at distal tips of sensory neurons
2) Initiate nerve impulse in response to stimulus
3) Nonencapsulated (free ending)- simplest receptor is bare axon
4) Most sensory nerve endings acquire CT capsules- encapsulated endings; many are mechanoreceptors located in skin and joint capsules

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What are three classifications of afferent receptors?

Back 112

1) Exteroceptors- react to stimuli from external environment (temp, touch, smell, sound, vision)
2) Enteroceptors- react to stimuli from within the body (degree of filling/stretch of alimentary canal, bladder, blood vessels)
3) Proprioceptors- react to stimuli from within body (sensation of body position, muscle tone and movement)

Front 113

What are some examples of mechanoreceptors of afferent receptors?

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1) Krause's end bulb
2) Ruffini's corpuscle
3) Meissner's corpuscle
4) Pacinian corpuscle

Front 114

Describe Meissner's corpuscles

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1) Small, oval in shape and found in dermis of skin
2) Detect light discriminatory touch- degree of discrimination determined by proximity of receptors to each other
3) LM appearance: CT capsule surrounding mass of oval cells arranged transversely at epidermal end (looks like tornado)

Front 115

Describe Pacinian corpuscles

Back 115

1) Large encapsulated receptors
2) Responsive to pressure or coarse touch, vibration and tension
3) Found in deeper layers of skin, ligaments, joint capsules, serous membranes, mesenteries, some viscera and in some erogenous areas
4) LM: onion-like appearache in cross section: CT capsule encloses concentric lamellae of flattened cells
5) Center of corpuscle contains single large unbranched, non-myelinated nerve fiber--> becomes myelinated as it extis
6) Distortion of corpuscle--> amplified mechanical stimulus in core--> transduces into action potential in sensory neuron

Front 116

What are the three divisions of the autonomic nervous system?

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1) Sympathetic
2) Parasympathetic
3) Enteric

Front 117

Describe the autonomic nervous system

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1) Has 3 divisions
2) PNS that innervates smooth/cardiac muscle and glandular epithelium
3) Visceral- refers to ANS or its neurons
4) Sensory neurons leave organs --> CNS (visceral afferent neurons)

Front 118

Describe the sympathetic divison of the ANS

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1) Fight or flight
2) Nerve cell bodies (preganglionic) located in thoracic and lumbar segments of spinal cord--> preganglionic axons exit CNS via ventral roots--> postganglionic fibers form later-vertebral chain and plexuses near viscera

Front 119

Describe the parasympathetic division of the ANS

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1) Rest and digest
2) Nerve cell bodies in medulla, midbrain and sacral region of spinal cord--> preganglionic axons exit via CN III, VII, IX, X and sacral spinal nerves II, III, and IV--> postganglionic neuron found in ganglia located near or within effector

Front 120

What happens when sympathetic and parasympathetic supply the same organs?

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Antagonistic actions
Example: sympathetic increases cardiac muscle contraction while parasympathetic decreases the contraction

Front 121

Describe the enteric division of the ANS

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1) Brain of gut
2) Can function independent of CNS
3) Ganglia and processes that innervate the alimentary canal; located in lamina propria, muscularis mucosae, submucosa, and muscularis externa
4) Fxn: controls motility (contractions of gut wall), exocrine and endocrine secretions, bloodflow through GI tract, regulates immunologic and inflammatory processes
5) Neurons not supported by Schwann or satellite cells; are supported by enteric glial cells (resembe neuroglial astrocytes)

Front 122

Describe the neuronal response to injury (degeneration)

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1) Anterograde (Wallerian) degeneration- region distal to site of injury degenerates due to interruption of axonal transport
2) In PNS, degeneration occurs within a few days; CNS takes several weeks
3) Axon degenerates by fragmentation; axon fragments still ensheathes by myelin
4) Phagocytic cells migrate to injury site and remove myelin/axon fragments (derived from Schwann cell in PNS; microglia in CNS; blood monocytes)
5) Some retrograde degeneration occurs; extends only few internodal segments
6) In PNS, Schwann cells with external laminae remain as tubular structures distal to injury

Front 123

Describe the morphological changes in neurons in response to injury

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1) Cell body swells, nucleus moves peripherally and chromatolysis (loss of Nissl substance) occurs
2) Chromatolysis first observed within 1-2 days and peaks ~2 weeks
3) Cell body changes proportional to amount of axoplasm lost by injury
4) If motor fiber is cut, the mucle innervated atrophies

Front 124

Describe scar formation

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1) In PNS, CT and Schwann cells form scar tissue between ends of injured nerve
2) If little scar tissue or surgical apposition, severed nerve will probably regenerate
3) In CNS, scar tissue derived from proliferation glial cells prevents regeneration

Front 125

Describe regeneration of neurons

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1) In PNS, required divison of Schwann cells (presence of endoneurium essential)- Schwann cells dedifferentiate and begin to secrete glial growth factors, which induces Schwann cells to undergo mitosis
2) Schwann cells form cylinders--> guide for new neurites (nerve processes) of regenerating axons
3) If neurite encounters Schwann cell cylinder, it begins to grow through tube at 3 mm per day, otherwise it grows in disorganized manner. Schwann cell contact with axon induces redifferentiation of Schwann cells
4) Upon crossing scar, neurites enter surviving Schwann cell tubes in distal stump--> guide to destination
5) If physcial contact is reestablished between motor neuron and muscle, function usually reestablished
6) Schwann cells remyelinate axon but length of internodal myelin usually shorter

Front 126

Describe peripheral neuropathy

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1) More than 100 different types; affects ~20 million individuals in US; 3-4% of >50 have a peripheral neuropathy (likely underdiagnosed)
2) Symptoms include: tingling, numbness, prickling sensations, touch sensitivity, muscle weakness, burning pain, muscle wasting, paralysis, organ and/or gland disfunction, muscle cramps
3) Caused by either inherited (gene mutation) or acquired trauma (carpal tunnel syndrome), toxins, tumors, autoimmune, nutritional deficiency (vit B12), systemic disease (diabetes), alcoholism, vascular disorder, metabolic disorder
4) Examples of acquired: Guillain-Barre syndrome: AKA acute inflammatory demyelinating polyneuropathy; due to autoimmune; results in ascending paralysis; a rare side-effect of various vaccines (influenza)
5) Examples of inherited: Charcot-Marie-Tooth disease- AKA heriditary motor and sensory neuropathy; affects 37 in 100,000; defects in forming myelin
6) If cause is autoimmune- treat by immune suppression; if cause is genetic, no treatment, treat symptoms
7) Diagnosed by: electromyogram- measures electrical activity of muscles at rest vs contraction, and nerve conduction study- measures how well and fast nerves send electrical signals
8) Damage to axon seen as loss of nerve/muscle potential amplitude; loss of myelin seen as decrease in nerve conduction velocity

Front 127

Describe amyotrophic lateral sclerosis (ALS, Lou Gherig's disease)

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1) Amyotrophic= muscle atrophy
2) Progressive degeneration of motor neurons of brainstem and spinal cord--> lateral sclerosis (tissue hardening) due to astrocyte gliosis (proliferation)
3) 5-10% of cases due to familial motor neuron disease (20% have mutation in gene superoxide dismutase 1- convert superoxide radicals to H2O2 and O2)
4) Sporadic ALS associated with Abs against voltage-gated Ca2+ channels
5) Average life expectancy from time of diagnosis is 2-5 years
6) No effective therapy although can slow progression of disease

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Describe Alzheimer's disease

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1) Progressive cortical dementia affecting language, memory, vision, emotion/personality
2) Familial forms--> mutations in presenilin 1/2 and B-amyloid precursor protein--> accumulation of abnormal large form of B-amyloid peptide and formation of amyloid plaques--> disrupt Ca2+ regulation--> causing neuron death
3) Presence of Hirano bodies- intracytoplasmic inclusions
4) Inheritance of 1 or more apolipoprotein Ee4 alleles (APOE locus; interferes with removal of large form of B-amyloid) indicative of susceptiblity risk factor, homozygous associated with earlier age of onset of common form of disease
5) No treatment- symptomatic therapy in early stages of dementia; Aricept (AChase inhibitor) controversial, no clinical evidence it halts progression of disease

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Describe Huntington's disease (chorea)

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1) Affects 1 in 10,000 people; children of affected patients have 50% chance of developing disease; DNA test to determine if mutation present
2) Mutation in HD gene results in increasing repeats of CAG--> amino acid glutamate--> programmed degeneration of basal ganglia neurons--> uncontrolled movements, loss of intelectual faculties and emotional disturbance
3) Large numbers of CAG repeats associated with early (childhood) onset of disease
4) No cure but can try to treat symptoms

Front 130

Describe Tay-Sachs disease

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1) Autosomal recessive disorder appears at ~6 months of age
2) Deficiency in hexosaminidase A--> accumulation of gangliosides in CNS neurons
3) Infants display characteristic cherry red spot in retina, delayed motor development, flaccid paralysis, weakness, blindness, mental impairment, and death
4) Histology- distension of CNS and PNS nerve cells with cytoplasmic lipid droplets; lysosomes filled with lipids (myelin figures)

Front 131

Describe shingles

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1) Re-remergence of nerve inflammation by herpes zoster (virus that causes chicken pox)
2) Results in painful skin lesions along dermatome (unilateral region of skin innervated by sensory fibers of single spinal nerve) of the infected nerve
3) Clinical presentation includes redness and vesicular eruptions of affected skin area