Download Histology of Nervous Tissue

Zoology 142
Nervous Tissue – Ch 12
Dr. Bob Moeng
Nervous Tissue
Homeostatic Control
• Nervous system and endocrine system are basis of homeostasis
– Nervous system responds rapidly (in msec)
– Endocrine system responds slowly
• Three major components of control
– Sensing internal or external levels
– Interpreting and integrating
– Reacting (motor) via muscle or glandular (effectors) stimulation
General Organization of NS
• Central vs. peripheral
– Central: brain & spinal cord
– Peripheral: cranial and spinal nerves
• Sensory (afferent) vs. motor (efferent)
• Somatic, autonomic & enteric
– Somatic (voluntary): sensory neurons from cutaneous and special sense receptors
and motor neurons to skeletal muscle
– Autonomic (involuntary): sensory neurons from visceral organs and motor neurons
to smooth & cardiac muscle and glands
– Enteric (involuntary): sensory neurons from chemical & stretch receptors in GI
tract, enteric plexus, motor neurons to smooth muscle and secretory functions
• Autonomic connections to CNS
• Sympathetic vs. parasympathetic
– Sympathetic: regulates energy expenditure
– Parasympathetic: regulates energy restoration and conservation
Organization of NS (graphic)
Histology of Nervous Tissue
• Major cell types
– Neurons (conducting cells) and neuroglia (support cells)
• Neuroglia
– Glia - glue; but much more
– 5-50X the number of neurons
– Can mitotically divide
Neuroglia
• Types
– Astrocytes: manage interstitial environment - metabolism of neurotransmitters,
balance of K+ ions, help form blood-brain barrier
– Microglia: protect CNS from foreign and damaged materials through phagocytosis
(derived from mesodermal cells that also give rise to monocytes & macrophages)
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Zoology 142
Nervous Tissue – Ch 12
Dr. Bob Moeng
– Ependymal cells: epithelial cells that line ventricles of brain & central canal of
spinal cord, produce CSF and promote its circulation (many are ciliated)
– Oligodendrocytes: most common glial cell in CNS, form myelin (w/o neurolemma)
– Neurolemmocytes (Schwaan cells): form neurolemma and myelin sheath around
neurons in PNS
– Satellite cells: support cell bodies in PNS ganglia
Types of Neuroglia (graphic)
Myelin
• Composed of lipid & protein concentrically laid membrane (up to 100 layers)
• Enhances rate of conduction of excitation and “insulates”
• Myelination different between CNS and PNS
• Presence of neurolemma increases probability of neuron regrowth
• Myelination increases during early childhood increasing rapidity and coordination of
response
• Multiple sclerosis
– Myelin produced by oligodendrocytes deteriorates
– Auto-immune response
– Slows conduction and short-circuits excitation
Formation of Myelin (graphic)
Gray and White Matter
• In CNS, clear difference between myelinated and unmyelinated tissue
• Gray - areas w/o myelin including unmyelinated regions of myelinated neurons,
unmyelinated neurons and neuroglia
• Brain: gray matter on outside of cerebrum and cerebellum and inner nuclei
(groupings of cell bodies and dendrites)
• Spinal cord: H-shaped gray matter inside
Gray vs. White (graphic)
Neuronal Structure
• Size
– Varying length: <1mm in CNS to >1.5 m in PNS
– Varying diameter: 5-135m which along with myelin affect conduction rates (1280mph)
• Major parts
– Dendrites (afferent) usually not myelinated, include rough ER (Nissl bodies),
mitochondria, and other cell organelles
– Cell body (or soma) include nucleus, Golgi, mitochondria, Nissl bodies, and other
cell organelles
• Clustered cell bodies in PNS form ganglia
– Axon (efferent) plus axon hillock, initial segment, axon terminal
• Nerve: in PNS, both sensory and motor neurons arranged in bundles
surrounded by connective tissue
• Tract: in CNS, bundled neurons w/o connective tissue
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Zoology 142
Nervous Tissue – Ch 12
Dr. Bob Moeng
– Synapse including synaptic end bulbs or varicosities with synaptic vesicles
Microanatomyof Neuron (graphic)
Tissue Cultured Neurons (graphic)
Relational Structure
• Multipolar - multiple dendrites and one axon
– Typical of brain and spinal cord
• Bipolar - one dendrite and one axon
– Typical of many sensory neurons including retina, inner ear and olfactory
• Unipolar - dendrite leads directly to axon
– Typical of sensory neurons for touch and pain
Sample Shapes (graphic)
Axonal Transport
• Slow axonal transport
– Similar to cytoplasmic movement in other cells but usually only toward axon
– 1-5 mm per day
• Fast axonal transport
– Organelle or molecular movement by protein motor, bi-directional
– 200-400 mm per day
– Important for long axonal lengths
– Various viruses and toxins transported this way
• Herpes & rabies virus, toxin from tetanus bacteria
Physiology of Excitable Cells
• Membrane potential: voltage difference between inside and outside of cell due to
ionic concentration differences (e.g. Na+, K+, Cl- and others)
– Resting potential - little current (ionic) flow
– Graded potential - varying current flow over a short distance
– Action potential - predictable current flow over a long distance
• Current flow due to combined ion movement through channels and pumps
Ion Channels
• Leakage (non-gated) channels (some always open)
• Gated channels (either opened or closed)
– Voltage gated - respond directly to changes in membrane potential
–
Ligand (chemically) gated - respond to neurotransmitters, hormones, H+ and Ca2+
• Direct or G protein/2nd messenger mediated
– Mechanically gated - respond to vibration, pressure or stretch
Ion Channels (graphic)
Resting Potential
• Polarization due to separation of charge across cell membrane
– Ranges from -40mV to -90mv in neurons (typical ~-70 mV)
– Due to concentration gradients of ions across membrane and relative permeability
of the ions through the membrane
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Zoology 142
Nervous Tissue – Ch 12
Dr. Bob Moeng
• Na+ and C- outside, K+ inside
• Permeability of K+ 50-100 > than Na+ (leakage channels)
– K+ equilibrium potential (-90 mV) has greatest influence over resting potential
• Membrane permeability greater for K+ than Na+ or Cl– Na/K electrogenic pump moves ions in 3:2 ratio
– Anions (Cl-) have little effect
Ions Across Membrane (graphic)
Graded Potentials
• Voltage change due to ion flow through chemically (ligand) or mechanically gated
channels
• Amount of voltage change (graded) dependent on # of gates open at one time and
how long
– Change is localized (not conducted)
– Change may be depolarization or hyperpolarization
• Usually limited to dendrites and cell body of neurons, and many sensory cells
• Synapse - postsynaptic potential, Sensory receptor - receptor potential, Sensory
neuron - generator potential
Graded Potentials (graphic)
Action Potential
• An all or none voltage change that starts when the neuron is depolarized to a
threshold level by graded potential(s)
• Carried (or conducted) over long distances
• Amplitude, period (about 1 msec) and conducting rate are dependent on nature of
neuron
• Primary carrier of information in nervous system either alone, in sequence or spatially
Phases of AP (graphic)
AP Depolarization
• Caused by rapid opening of voltage-gated Na+ channels to where polarization is
reversed
• Channels open at a threshold level (neuron specific) - ~-55mv
• Initially Na+ is driven by both concentration & electrical gradients
• Voltage-gated Na+ channels have an activation & inactivation gate
• Activation gates opened by super-threshold voltage
• Inactivation gates closed after specific period of time (a few 10,000th of a sec)
• Number of Na+ ions that move are small relative to total concentration outside cell
thus little change in gradient (important for next AP)
• Electrogenic pump return the Na+ ions to exterior
• Local anesthetics frequently prevent opening of Na+ channels (e.g. Novocaine or
Lidocaine), also tetrodotoxin
AP Gate Action (graphic)
AP Repolarization
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Nervous Tissue – Ch 12
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Dr. Bob Moeng
Voltage-gated K+ channels also open at threshold, but slowly
K+ ion movement more evident (repolarization) as Na+ channels close
Voltage current is reversed bringing neuron back to resting potential (usually some
hyperpolarization prior to all K+ channels closing)
Refractory Period
• Absolute refractory period - neuron cannot be re-stimulated (Na+ channels are
inactivated with both gates closed)
• Relative refractory period - neuron can be stimulated by suprathreshold level (K+
channels are still open)
• Refractory period determines rate of AP generation (frequency)
– large diameter cells - ARP about 0.4 msec (2500 APs per sec)
– small diameter cells - ARP about 4 msec (250 APs per sec)
AP Conduction
• Or propagation
• In unmyelinated neuron, current flow in one membrane region affects voltage in
adjacent region - continuous conduction
– If Na+ channels are in resting state, they are activated
– If Na+ channels are in inactive state, there is no effect
– Thus APs are conducted in one direction
• In myelinated neuron, current flow is through nodes of Ranvier only - saltatory
conduction
– Na+ and K+ channels open in nodal regions only
– Thus AP jumps from node to node increase rate of conductance
– Fewer membrane channels open per unit length of neuron decreasing the required
work of the electrogenic pump
AP Conduction (graphic)
Conduction Rates
• Conduction rate is dependent on neuron diameter as well as presence of myelin
• A fibers - diameter of 5-20 m, short absolute refractory period, with conduction rates
12-130 m/sec
– Typical of sensory and motor neurons needed for quick response
• B fibers - diameter of 2-3 m, longer absolute refractory period, with conduction rates
15 m/sec
– Typical of visceral sensory and ANS motor neurons to autonomic ganglia
• C fibers - diameter of 0.5-1.5 m, longest absolute refractory period, with conduction
rates 0.5-2 m/sec
– Typically unmylenated neurons, many peripheral neurons associated with pain,
and post-ganglionic ANS motor neurons
Synapse
• Functional junction between neurons and between neuron and effector
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Zoology 142
Nervous Tissue – Ch 12
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Dr. Bob Moeng
Gap junctions are a form of electrical synapse (e.g. intercalated discs of heart muscle,
also CNS) - two way flow & fast
• Chemical synapses (e.g. NMJ) - one way flow & slower
– Review components
– Synaptic delay about 0.5 msec
Synaptic Action
• AP arrives at presynaptic region of axon
• Voltage-gated Na+ and Ca2+ channels open
• Ca2+ moves inward
• Ca2+ initiates exocytosis of synaptic vesicles
• Neurotransmitter diffuses across synaptic cleft (20-50nm) and bind to receptors
• Neurotransmitter receptors on postsynaptic membrane open ligand- gated ion
channels
• Na+, Ca2+ inflow - excitatory
• K+ outflow or Cl- inflow - inhibitory
Synaptic Action (graphic)
Postsynaptic Potentials
• Excitatory or inhibitory potentials depend on the neurotransmitter, receptor, and
channels opened (EPSP or IPSP)
• They are graded potentials (not propagated, varying amplitude, no refractory period)
• Excitatory - opening of cation channels allowing flow of Na+, Ca2+, and K+
– Since Na+ furthest away from its equilibrium potential, more Na+ flow
• Inhibitory - opening of Cl- or K+ channels
Excitatory Synapse (graphic)
Removal of Neurotransmitter
• Diffusion
• Enzymatic breakdown
– e.g. acetycholinesterase
• Recycling uptake
– By presynaptic neuron or neuroglia
– Involves neurotransmitter transporters in membrane
– Cocaine blocks transporters of dopamine (brain NT) causing heightened
stimulation
– Prozac (anti-depressant) inhibits uptake of serotonin
Postsynaptic Summation
• CNS neurons may have 1000s of synapses
• Spatial summation
• Temporal summation
• Summed effect on postsynaptic cell
– Excitatory PSP
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Zoology 142
Nervous Tissue – Ch 12
Dr. Bob Moeng
– Action potential (sufficient EPSP at initial segment)
– Inhibitory PSP
Examples of Summation (graphic)
Neurotransmitters
• 100 or so possible substances
• Modulation
– Rate of synthesis
– Blocked or enhanced release
• Botulinum toxin inhibits release of ACh
– Inhibited or enhanced removal
– Blocked or enhanced active site
• Curare blocks ACh receptors
• Agonist vs. Antagonist
– Therapeutic/drug related
Acetylcholine
• PNS neurons and some CNS neurons
• Excitatory in NMJ
• Inhibitory at heart via G protein/2nd messenger (parasympathetic vagus)
Amino Acids
• Glutamate and aspartate
– Excitatory in CNS (some w/Ca+ gates)
– Glutamate ~half of brain synapses and removed by transporters
• Gamma aminobutyric acid (GABA) and glycine
– Inhibitory via Cl - channels
– GABA most prevalent inhibitory transmitter in brain
– Valium (diazepam) is an agonist for GABA
– In spinal cord, both about equally found
Biogenic Amines
• Catecholamines including nor-epi, epi and dopamine
– Derived from tyrosine
– Can be either excitatory or inhibitory
– Removed by transporters to pre-syn. membrane
– Rigidity of skeletal muscle in Parkinson’s disease due to relatively low dopamine
production (inhibitory in brain)
• Serotonin (5-hydroxytryptamine)
Adenosine Derivatives
• Adenosine, ATP, ADP, AMP
• Excitatory in CNS & PNS
• Frequently co-released with other transmitters
Nitric Oxide Gas
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Derived from arginine
Not packaged, but enzymatically formed as released
Short-lived (10 sec)
Lipid soluble (diffuses through membrane) - no vesicles, no receptor channels; 2nd
messenger (GMP) in post-synaptic cell
• Produced by endothelial cells of vessels to relax smooth muscle (↓BP); Viagra ↑ NO
effect
• Transmitter in brain and ANS
Neuropeptides
• CNS & PNS
• Excitatory & inhibitory
• Manufactured in cell body
• First found when looking for effects of opiates
• Include enkephalins, endorphins, dynorphins
• Bodies natural painkillers? Effects of acupuncture?
• Substance P – for communication of pain (PNS to CNS)
– Inhibited by enkephalins
• Others: Angiotensinogen II, CCK, releasing and inhibiting hormones from
hypothalamus
Neural Circuits
• Simple series - no integration
• Diverging
– Increased number of terminal neurons; distribution to multiple regions
• Converging
– Increases likelihood of excitation or inhibition of terminal neuron or effector
• Reverberating
– Causes repetitive stimulation in terminal neuron
– Inhibition required to stop
– May be important for breathing, muscle coordination, short-term memory
• Parallel after-discharge
– Causes extra EPSP or IPSP in terminal neuron
Integrating Circuits (graphic)
Regeneration
• Plasticity - new dendrites, synapses
• In PNS, dendrite or axon w/o neurolemma damage may repair
– Chromatolysis (breakdown of Nissl bodies), Wallerian (distal) degeneration, mitotic
division of neurolemmocytes and formation of regeneration tube
• In CNS, neither unmylenated or mylenated (by oligodendrocytes) neurons regenerate
– Astrocytes fill space
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– Research - stem cells & epidermal growth factor
Regeneration (graphic)
Epilepsy
• READ
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Dr. Bob Moeng