Notes
on the Web
Nervous
System: Histology and Physiology
Bruce G. Stewart
Related Textbook Readings
Selected Images of Histological Materials From Laboratory Studies
Related Human Anatomy Coloring Book Assignments
Lecture Outlines
I. Nervous System and Tissue Fundamentals
A. Basic functions
1. As a controlling and communicating system of body
a. works with endocrine system to regulate and maintain homeostasis
b. more rapid than endocrine system
2. Detects, interprets and reacts to internal and external changes
a. sensory input from stimuli
- stimulus - a change that can be detected by the NS
b. integration - interpretation and decision-making
c. motor output - activates muscles, organs and glands
B. Organization (refer to appropriate text figure and memorize)
1. Two major subdivisions
a. Central nervous system (CNS)
- components - brain and spinal cord
- general functions - integration and control centers
b. Peripheral nervous system (PNS)
- components - cranial, spinal and associated nerves
- general functions - communication lines between CNS and rest of body
- subdivisions of PNS
- sensory (afferent) division - carries impulses to the CNS
- somatic afferents - from skin, skeletal muscles, and joints
- visceral afferents - from visceral organ
- motor (efferent) division - carries impulses from CNS to the other body organs, muscles and glands
- divisions of the motor division
- somatic (SNS) - from CNS to muscles of skeleton - voluntary control
- autonomic (ANS) - from CNS to smooth muscles, cardiac muscles, and glands - involuntary control
- divisions of the autonomic nervous system
- sympathetic and parasympathetic - have contrasting actions of stimulating (mobilizing the body for emergencies) and inhibiting (slowing down activities to conserve energy when possible)
II. Histology of Nervous Tissue
A. Cell Types
1. Neuroglia - cells that perform functions of support and protection.
a. ectodermal origin and 5-10x more common than neurons
b. twine around neurons or form linings in brain and spinal cord
c. types
- astrocytes - bind neurons to supporting structures and to blood vessels
- oligodendocytes - produce phospholipid (myelin) sheath around nerve fibers (axons) of CNS and bind nerves to each other
- microglia - phagocytic
- ependyma - ciliated and line ventricles of brain and central canal of spinal cord help; circulate cerebrospinal fluid
d. glial cells are a common source of tumors
2. Neurons- cells that conduct nerve impulses
a. basic structure
- cell body (= soma or perikaryon)
- has typical organelles but lacks the mitotic apparatus (usually)
- also has many intermediate filaments that serve roles in transport
- dendrites - cytoplasmic processes that receive stimuli and send to cell body
- axon - single, long slender cytoplasmic process that conducts impulses away from cell body
- axoplasm has abundant mitochondria and neurofibrils
- range from 1 mm (e.g. in brain) to 1 m (between spinal cord and toes)
- movement of synthesized materials
- axoplasmic flow - unidirectional, slow diffusion based flow (e.g. 1 mm/day)
- axonal transport - bidirectional, rapid movement (e.g. 300 mm/day)
- telodendria - branching end of axon with specialized terminals for communicating information to next cell (glandular, muscular or nervous)
- synaptic end bulbs
- synaptic vesicles
- neurotransmitters
- myelin sheath - white phospholipid coil (often 20-30 coils) around the nerve fiber (generally the axon)
- in the PNS - produced by neurolemmocytes (= Schwann cells)
- in thePNS - the cell body and membrane with most of the Schwann cell cytoplasm is called the neurilemma; this part is especially important in axon and dendrite repair (and thus nerve repair)
- in CNS - oligodendrocytes produce a myelin sheath but there is not a neurilemma component; this does not allow fiber repair
- in both PNS and CNS the myelin sheath facilitates neurotransmission
- neurofibril nodes (= Nodes of Ranvier) - gaps between Schawnn cells of PNS which allow for a fast and efficient type of transmission called saltatory conduction
- CNS possesses continuous myelination along fibers
- 1st laid down in latter part of fetal development - increases with age and accounts in part for increases in response time and coordination during developmetn after birth
b. growth and activity - affected by hormones such as the Nerve Growth Factor
c. Note the many structural variations in neuron types in textbook; we will review these in lecture class.
Laboratory Exercise - Nerve Tissue Histology
At this point we will conduct laboratory studies of a number of nerve tissue slides. You will look in detail at nerve cross-sections and medullated nerves. Here are some of the required structures for each.
Other demonstration slides will be shown with the videomicroscope and projected on the screen in the classroom. These include an H&E stained preparation of a nerve cross-section, a slide showing teledendria and synaptic end bulbs associated with innervated skeletal muscle tissue, and some miscellaneous brain tissue preparations. Required knowledge of these slides will be noted in lecture or lab.
Video
Histology Series - Nerve Tissue
Dr.
David Moran - Colorado State University
At this point we will view an excellent video histology presentation by Dr. David Moran. You can consider him to be a "visiting lecturer" throughout the semester since we will view video histology presentations by him on almost all major tissue types found in the human body systems we cover. We will always view these after we have completed our own lab exercises so that you will be better prepared to understand the presentations. Do not take these lightly since they can add a useful perspective on tissue structure, and Dr. Moran presents images taken with types of microscopes we do not have (e.g. scanning electron, transmission electron, Nomarski interference contrast, and phase contrast microscopes). He also shows images of materials prepared with different histological stains and techniques that enhance the quality of images.
Lecture Outlines (continued)
III. Physiology of Nerve Impulses
A. Two major features of neurons:
1. highly developed ability for generating and conducting electrical messages (=impulses)
2. limited ability to regenerate
B. Nerve impulses
1. membrane potentials - differences in ion concentration outside vs. inside the plasma membrane
a. resting neuron has difference of -70mV (note that 1.5-volt battery will power a flashlight)
- negative charge indicates that the inside is less positive than outside
b. potentials are created due to differences in simple ions including K+, Na+, and organic phosphate and protein anions
- note that the large anions cannot move through membrane and thus are held on inside
- sodium-potassium pump is responsible for differential
- uses ATP
- pumps Na+ out and K+ in but in 3:2 ratio
- Na+ is 14x in much greater outside at resting while K+ is 28-30x more concentrated inside (but note difference in concentration of both of Na+ and various anions)
- also K+ leaks out (100x more leaky than Na+ leaking in) and this further reinforces the negative resting potential
2. Excitability - ability of nerve cells to respond to stimuli and convert them into impulses
a. stimulus - any condition capable of altering the resting potential
- threshold stimulus - adequately strong to cause an impulse
b. voltage-sensitive sodium channels - protein pathways that can open and allow Na+ influx
- Na+ follows its own diffusion gradient and is attracted to anions inside cell
- depolarization - change in membrane potential after channels open
- moves from -70mV to +30mV
- each channel has activation gate and inactivation gate: the later closes shortly after Na+ influx (only few thousandth of a second later!) and allows recovery
c. nerve impulse (nerve action potential)
- positive feedback from one area spreads down neuron as other channels open
- about 1 msec long
d. repolarization
- voltage-sensitive potassium channels open after sodium channels close
- K+ diffuses outward
- active transport with sodium-potassium pump restores resting potential
- refractory periods (r.f.)
- absolute r.f. - time for another impulse to be possible (e.g. 1/2500 sec or .4 msec for large fibers and 1/250 sec or 4 msec for small fibers)
- relative r.f. - time when stronger than normal threshold stimulus can start impulse
e. Muscle Action Potentials (MAPS) are similar to Nerve Action Potentials (NAPS) but some differences exist (e.g. -90mv membrane potential and slower impulse of 1-5 msec and velocity is 1/18th of nerve action potential
f. All-or-none principle
- threshold stimulus required to initiate impulse
- subthreshold stimulus does not initiate impulse unless cummulative
3. Saltatory conduction vs. continuous conduction
a. continuous conduction occurs in non-myelinated neurons
b. saltatory conduction occurs in myelinated neurons
- depolarization occurs in neurofibril nodes
- impulse "leaps" to next node by ion flow in axoplasm and extracellular fluids
- is faster and saves ATP energy since Na+/K+ pumping needs are less
4. Speed
a. A fibers - fastest (130 m/sec)
myelinated, large, short refractory period
typical of sensory neurons such as in touch, pressure, position of joints, heat and cold.
also typical of motor neurons that control response muscles
b. B fibers - medium (10 m/sec)
- myelinated, medium size
- skin and viscera to brain and spinal cord and some efferents from lower brain to ganglia that link to smooth muscles and glands
c. C fibers - slow (.5 m/sec)
- myelinated, smallest
- similar function as B fibers (e.g. functions of the autonomic nervous system)
C. Conduction across synapses and junctions
1. Neuroeffector junctions
a. neuromuscular junction
b. neuroglandular junction
2. Synapses
a. general structure and types
- presynaptic neuron vs. postsynaptic neuron
- synaptic cleft (20 nm)
- synaptic end bulbs
- axodendritic (dendrite) vs. axosomatic (cell body) vs. axoaxonic (axon hillock)
- divergence (serves several neurons) vs. convergence
- electrical (with gap junctions) vs. chemical (most common and with neurotransmitters)
b. chemical synapses
- neurotransmitters
- produced in cell body and transported to end bulb
- held in 1000's of synaptic vesicles with 10,000-100,000 molecules each
- impulse causes release of neurotransmitters into synaptic cleft
- neurotransmitter molecules attach to receptors on postsynaptic neuron and cause depolarization
- size, shape, and arrangement of charges on all molecules is crucial to their function (analogous to a lock and magnetic card key)
- one-way conduction
c. excitatory transmitter-receptor interactions
- lower (make less neg.) the postsynaptic membrane potential (facilitation)
- spatial summation (from different end bulbs)
- temporal summation (from repeated firing of single end bulb)
- --> last about 15 msec so second firing must happen quickly
d. neurotransmitter receptors (channels for Na+ vs. enzymatic activation)
- first mechanism - neurotransmitters e.g. acetylcholine bind to proteins on post synaptic plasma membrane and opens Na+ gates
- second mechanism - neurotransmitters e.g. catecholamines (norepinephrine, epinephine, and dopamine) bind to receptors and activate an enzyme (adenylate cyclase)
- adenylate cyclase converts ATP into cyclic AMP which activates other enzymes which open sodium channels
- --> the first messenger is the neurotransmitter
- --> the second messenger is the cyclic AMP
D. Inhibitory Transmission
1. Inhibitory transmitter-receptor interaction
a. hyperpolarization - making the membrane potential more negative (thus increasing the threshold stimulus required)
- Inhibitory postsynaptic potential (IPSP) caused by greater permeability to Cl- and K+ (lasts only milli-seconds)
b. presynaptic inhibition - inhibitory neurons synapse also with excitatory synapse and can depress response (lasts several minutes)
E. Integration
1. Postsynaptic neuron is integrator
a. can react differently depending on relative strengths of inhibitory and excitatory stimuli.
F. Some Other Neurotransmitter Examples
1. Acetylcholine (ACh) - protein which is released from synaptic end bulbs after the arrival of the nerve action potential which causes Ca2+ influx which causes synaptic vesicles to be released.
a. deactivated by acetylcholinesterase (AChE) which is found on outer edge of subneural clefts within 1/500th sec.
- broken down into acetate and choline
b. choline reenters synaptic end bulb and is combined with acetate again (enzyme - choline acetyltransferase)
c. cycle repeated
d. ACh is generally excitatory in a variety of muscle types and neuroglandular junctions (but inhibitory at vagus nerve X which affects the heart)
2. gamma aminobutyric acid (GABA) - inhibitory in CNS by causing hyperpolarization
a. a medication, Baclofen, is a valuable molecular mimic of GABA and is used to reduce muscle spasms due to spinal cord injury paralysis and some other injuries and illnesses. Baclofen can be taken orally, but sometimes its cerebral spinal fluid (CSF) concentration cannot reach clinically-useful levels. In such cases, a catheter can be used to inject the medication directly into the CSF by using a computerized pump to deliver the proper dosages. This bipasses the blood-cerebral spinal fluid barrier to accomplish the desired clinical results.
3. glycine - amino acid that is inhibitory in certain spinal cord neurons
IV. Clinical Applications
A. Disease-related alterations in synaptic conduction
1. myasthenia gravis - antibodies attack ACh receptors on skeletal muscle fibers at neuromuscular junctions (messes up contractions)
2. alkalosis - increase pH above 7.45 causes increased excitability of neurons and results in
a. lightheadedness, numbness around mouth, tingling in fingertips, nervousness, muscle spasms, and convulsions
3. acidosis - decrease in pH below 7.35
a. can arise because of high blood sugar in people with diabetes
b. apathy, weakness, comatose state - can be mistaken for drunkenness
B. Medical drugs can alter synaptic conduction
1. Curare - drug that competes for ACh receptor sites
a. muscle relaxation (sometimes used during surgery)
2. Neostigmine and physostigmine - anti-acetylcholinesterase and thus increase affects of stimulation by ACh
a. neostigmine is used as an antidote for curare
b. both used to treat myasthenia gravis and glaucoma (drops of physostigmine constricts pupil)
3. Hypnotics, tranquilizers, and anesthetics - depress synaptic conduction by increasing the threshold for excitation of neurons
4. Benzedrine - example of a stimulator through facilitation of conduction
C. Many other chemicals have impacts on synaptic conduction
1. Diisopropyl fluorophosphate - nerve gas in many insecticides which inactivates acetylcholinesterase for weeks! Lethal.
2. Botulism toxin - inhibits ACh and is very potent (in amounts as small as .0001mg!) and is a deadly food poison
D. Drugs of abuse and recreation have impacts on synaptic conduction
1. Caffeine - a stimulant through facilitation of synaptic conduction
2. Nicotine - a highly addictive stimulant that acts as a facilitator of synaptic conduction
a. stimulates the reward system of the brain (we will discuss this later)
b. smokers misinterpret the "calming" affect of smoking; it is actually calming only in the sense that it removes withdrawal symtoms of craving.
c. one of the most abused central nervous system stimulant on earth, and produces great health damage to individuals and great economic and social damage to society.
3. Cocaine, Methamphetimines, Heroin, Morphine, and several other drugs will be covered in detail separately.(see: http://www.mscok.edu/~bstewart/bstewart/classes/anatomy/addictphys.htm)
a. preview note - cocaine interferes with dopamine reuptake in the mesolimbic dopamine system of the brain and therefore affects mood regulation.
b. at first euphoria results but also later creates shortage of neurotransmitters and results in depression and other serious mental malfunctions.
c. all addictive drugs (whether legal or illegal) have been implicated in stimulating the mesolimbic dopamine system. As noted previously, this important component of the central nervous system will be explored in detail in a separate set of Notes on the Web in this unit.
E. Physical pressure causes alterations in blood flow to nerves and sensory receptors and thereby alters the efficiency of synaptic conduction
1. Causes tingling due to build up of wastes and depressed circulation.
Reminder about Textbook Study
As with other topics, your textbook has excellent presentations of the materials on the histology and physiology of the nervous system. While you should focus on the specific material in the Notes on the Web, you should always use your textbook as a resource for illustrations and for understanding content that your notes cover.
As with all materials throughout the semester, you will have opportunities to ask questions or ask that any relevant material from your assignments be discussed in class.
Related Internet Resources