MCB 32 Introductory Human Physiology
Notes for Tuesday, September 12
Chapter 3, pps. 63-71, Chapter 4, pps.75-84.
OUTLINE FOR LECTURE
l. Synaptic Transmission
ll. Chemical Communication
lll. Neurophysiology
lV. Brain structure
l. Synaptic Transmission (Figure 3.15, p. 65)
The transfer of information from a neuron to another cell by chemical means is called synaptic
transmission.
The nerve impulse cannot pass from one neuron to the next because there is no direct connection
between the two neurons.
Communication between a neuron and another cell is the function of specialized junction called
the synapse.
The action potential produces the release of a chemical from the axon terminal of a presynaptic
neuron. The neurotransmitter, in turn, acts on a postsynaptic neuron.
The released chemical is called a neurotransmitter because of its function as a transmitter of
information and because it is released by a neuron.
Typically, the axon terminal of the presynaptic neuron synapses with the dendrite or cell body of
the postsynaptic neuron.
Keep in mind that although we are describing how information is passed from one neuron to the
another, neurons also form synapses with other cell types, including muscle cells, glands and
other tissues.
The Synapse
Th
axon terminal of a presynaptic neuron ends in a rounded structure called the presynaptic bulb.
The synaptic bulb contains packets of chemical neurotransmitter packaged in small membranebound vesicles.
When an action potential arrives at the synaptic bulb, a series of events is initiated that ultimately
result in movement of these vesicles to the cell membrane.
There the vesicles fuse with the cell membrane, releasing their contents into the space between
the presynaptic and postsynaptic cells; this space is known as the synaptic cleft.
Because the synaptic cleft is rather narrow, some of the neurotransmitter can reach the
postsynaptic cell membrane by diffusion. At the postsynaptic cell membrane the neurotransmitter
binds to the receptor, which results in changes in membrane permeability to certain ion such as
Na+.
This, in turn, produces a small graded depolarization of the postsynaptic cell membrane in the
area of the synapse.
The production of the graded potential that we talked about in the last lecture is in fact, the
graded potential produced by synaptic transmission.
The chemical substances that we alluded to earlier are the neurotransmitters released by
presynaptic neurons.
The development of graded potentials at the synapses on dendrites and cell body of a neuron, if
sufficiently summated result in an action potential. The action potential travels down the axon,
producing the release of neurotransmitter, which, in turn produces a graded potential in the next
neuron and so on.
Whether a postsynaptic neuron will generate an action potential depends on the sum of all the
graded potentials it receives.
In fact, a single synapse is unlikely to cause the generation of an action potential in the
postsynaptic neuron.
A postsynaptic cell may have hundreds synapses with dozens of presynaptic neurons.
Only when the en
re sum of positive and negative infuences from many synapses produces a net graded
depolarization at the axon
llock of about -55 mV will an action potential be initiated.
Termination of synaptic transmission
Earlier, we mentioned that graded potentials may be short-lived, decaying rather quickly over
time.
This is because the neurotransmitter substances remain in the synaptic cleft for only a short
period of time, and the increase in postsynaptic cell membrane permeability to Na+ is directly
related to the concentration of neurotransmitter.
There are three possible fates of neurotransmitter that is released into the postsynaptic cleft:
1) it may diffuse out of the synaptic cleft into the general circulation, where it is
ultimately destroyed
2) it may be degraded by special enzymes produced by either the pre- or postsynaptic
cell or
3) it may be taken back up by the presynaptic cell and repackaged into membranebound vesicles, to be used again.
The interference with neurotransmitter uptake accounts for most of the actions of of cocaine,
some antidepressive drugs.
Together, these three mechanisms of neurotransmitter removal ensure the stimulus can be
terminated as quickly as it can be initiated.
Speed of synaptic transmission
The rate of transmission of information across the synapse is considerably slower than the rate of
conduction of a nerve impulse down an axon.
This synaptic delay, on the order of 1/2000th of a second is due to the time it takes for
neurotransmitter to be released from the presynaptic cell, to diffuse across the synaptic cleft, and
to activate the postsynaptic cell to become permeable to Na+, as well as the time for Na+ to enter
the cell and produce a graded potential, and then a nerve impulse.
Given these steps, 1/2000th of a second seems relatively fast. Nevertheless, it is considerably
slower than the speed of conduction of action potentials.
Neurotransmitter substances and receptors
The human body actually uses several dozen different neurotransmitter substances, each with its
own particular mode of action and effect on the postsynaptic cell.
As mentioned earlier most neurotransmitters produce a depolarizing graded potential, increasing
the chance that the threshold will be reached and that an action potential will be generated by the
postsynaptic neuron or cell.
Others produce hyperpolarizing graded potentials in the postsynaptic cell, reducing the chance
that threshold for an action potential will be reached.
Most neurons produce primarily one neurotransmitter at their axon terminals.
Some neurotransmitter substances exert an excitatory influence on one postsynaptic cell type and
an inhibitory influence on another.
They can do this because different receptor subtypes can exist for a single neurotransmitter.
Activation of different receptor subtypes can produce very different postsynaptic events.
Four of the most common neurotransmitter substances are acetylcholine (ACh), norepinephrine,
(NE), epinephrine(E) and dopamine (DA).
Acetylcholine is the neurotransmitter found at the junction between a neuron and a skeletal
muscle, where it stimulates the muscle to contract.
It also inhibits the rate at which the heart beats.
ACh is an example of one neurotransmitter producing both stimulatory and inhibitory actions,
depending on type of receptor it actiates.
Norepinephrine, epinephrine, are found widely in the brain.
Norepinephrine is also the neurotransmitter for a branch of the nervous system that regulates
many of the automatic functions, such as blood pressure and rate of breathing.
Neural Information Processing
So far we have described how an action potential, or nerve impulse is generated in a nerve cell
and transmitted from a nerve cell to another cell. These nerve impulses form the basis of rapid
communication throughout the body.
If all information is in the form of identical electrical impulses, how can one perceive all of the
colors in a sunset, feel emotions, or guide a basketball into a hoop from a distance of 20 feet?
This is a very active area of research. Some of the biological phenomena that probably contribute
to information processing and integration are discussed below.
The areas of the brain that receive the nerve impulses and how they are processed by the brain are
very important in determining how information is perceived.
Convergence and divergence of neural information
Information is not transmitted strictly from one nerve cell to another in a straight line.
Many different presynaptic cells may form synapses with a single neuron; this joining of output
of many presynaptic cells onto one postsynaptic cell is called convergence.
In humans terms, an example might be the sight of a steak, the sizzling sound it makes on a grill,
and its smell may all provide information (via neurons and their synapses) to one neuron that
contributes to the feeling of hunger.
Furthermore, one nerve cell can provide information to a variety of postsynaptic cells, a process
called divergence.
In the example of a 20-foot jump shot, information from a single visual cell in the eye may
provide information to different areas of the brain, involved in vision, control of muscle
movement, memory, and even emotions.
Coding for stimulus intensity
The coding for stimulus intensity is in part determined by how many neurons in a given pathway
are active and by the number of action potentials per unit time in a given neuron. The latter can
vary from zero in an inactive neuron up to several hundred impulses per second.
Neurons vary considerably both in the threshold membrane potential required to initiate an action
potential and in the maximun number of action potentials per unit time.
Because action potentials are conducted in an all-or-none fashion and do not vary in amplitude as
they travel down a neuron, intensity is not encoded by action potential amplitude, but by
frequency.
Inhibitory versus stimulatory input
As mentioned previously, synaptic input to a neuron can either increase of decrease the
likelihood that the neuron will initiate an action potential. This depends on the type of
neurotransmitter released and the type of receptor present on the postsynaptic membrane.
Direct electrical communication.
Electrical impulses generated by neurons are usually transmitted to adjacent neurons by a
chemically mediated step because the distance between the two cells is too great for direct
electrical transmission.
However, there are important exceptions. A few excitable cells are capable of direct electrical
connections. The most important of these include certain muscle cells, particularly those of the
heart and digestive tract.
Cells in these muscles are joined together by special connections known as gap junctions. Gap
junctions are composed of membrane proteins that span the gap between adjacent cells, forming
a direct channel between them.
Muscle cells joined by gap junctions can transmit electrical information in the form of ions
directly from cell to cell, so that the action potential proceeds not just down the length of a single
cell, but through all the muscle cells in the tissue.
This is the basis for the coordinated contraction of the heart, and for the process to move food
through the digestive tract.
Some nerve cells also have gap junctions, called electrical synapses, but the chemical synapse is
by far the more common.
Chemical Communication
Every form of communication except direct electrical connections between certain muscle cells
relies, at least in part, on chemical messengers.
The classification of chemical messengers into subgroups relies primarily on the type of cell that
releases the chemical and on how the chemical reaches its site of action.
Hormones
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classical definition of a hormone is a chemical that is secreted by a gland into the bloodstream
traveling to other sites in the body to exert its effect.
The site at which the hormone acts is called the target. A single hormone may have only one
target tissue or organ or it may have many diverse targets and thus many regulatory effects.
Hormones control processes as diverse as the rate of urine formation, the amount of sugar in the
blood, and the rate of sexual maturation.
Hormones act on specific cells. This is because the target cell needs to have a specific receptor
for that hormone in order for it to respond.
To make things more complicated, different cells may have different receptor types for the same
hormone. It is the special properties of these receptors that determine the effect elicited by the
hormone.
Paracrine and Autocrine Factors.
Numerous chemical messengers have been discovered that do not fit the classical definition of
hormone.
Some cells communicate with nearby cells by releasing chemicals into the extracellular space.
These chemicals function as messengers even though they do not circulate in blood. Such local
chemical messengers are called paracrine factors.
Examples of paracrine factors are histamine and prostaglandins.
Histamine is a chemical released from specialized cells called mast cells that are present in most
tissues. It is responsible for local swelling of a tissue when it is damaged, and for some of the
effects of allergic reactions.
Prostaglandins are a family of fatty acids found in almost every tissue and organ in the body.
Prostaglandins have a variety of roles in local tissue function, including constriction or dilation of
blood vessels, blood clotting and promotion of inflammation. The various growth factors that
have been identified in a number of tissues and organs are also paracrine factors.
In general, paracrines factors are synthesized and released in the vicinity of their target cells.
Autocrines
Chemical messengers that act directly on the cells that produce them. Inhibitors of cell
reproduction are paracrines and autocrines. One of the defects of cancer cells may be that they
lack these inhibitors or do not respond to them, so that cell division continues unchecked.
Neurohormones
Some neurons called neuronendocrine cells do not synapse with another neuron; instead, their
axon terminals are located near blood vessels. Neuroendocrine cells release their chemical
messengers, call neurohormones, directly into the bloodstream.
An example of a neurohormone is oxytocin. Oxytocin is carried in the blood to the mammary
gland, where it is responsible for milk ejection.
Neurophysiology
The brain receives input from the external world and your internal world and integrates those
signals so as to adjust the output in order to maintain homeostatic balance.
It integrates many inputs such as vision, sound, touch and position and responds appropriately.
It Initiates movement, thought, speech and all that makes us uniquely human.
The brain is also the organ that controls that most illusive property, consciousness.
Our understanding of brain function came slowly from careful anatomical observations and from
many animal experiments in which parts of the brain were removed or stimulated electrically.
Early anatomists recognized that the brain was not a homogeneous organ but rather is composed
of discrete parts, many of which could be easily identified.
Furthermore, the brain is attached to the spinal cord, from which numerous nerves exit and and
travel to the muscles and organs of the body.
Indeed, no part of the body is free of innervation. Thus, the brain seemed to be an organ centrally
located and well designed to coordinate body functions.
By the middle of the nineteenth century, anatomists performed ablation (surgical removal)
experiments in an attempt to understand the brain’s function.
Among the first were studies in which they removed small parts of the brain from hens.
Depending on which part of the brain was surgically removed, they observed a different deficit.
Removing parts of the lower brain, the medulla, interrupted normal respiration.
If parts of the outermost brain, or cerebrum, were ablated the hen “lost instincts”, meaning it
would no longer eat or perform other normal activities.
These types of crude studies clearly indicated that the brain controls many functions, and that
different areas of the brain serve different functions.
Electrical studies were an outgrowth of the realization that specific brain areas have specific
functions.
As you learned in earlier lecture, a weak electrical current applied to a nerve causes the nerve to
generate an action potential that is then propagated down the nerve. This led researchers to test
the results of stimulating the brain surface with a weak electrical current.
They demonstrated that electrical stimulation of a discrete area of the brain of an anesthetized
animal might cause a limb to move in a particular direction. Stimulation of another spot on the
surface of the brain might cause a digit to contract. Stimulation of a specific brain area always led
to the same effect.
Anatomical studies, coupled with electrophysiological ones, detailed much of what we know
about brain function.
Structure of the Nervous System
The nervous system is composed of all the neural elements of the body.
A clear division can be made between the elements contained in the bony structures of the body,
the skull and the spinal column, and the neural elements outside the bony case.
The former is called the central nervous system (CNS).
The latter, which includes all the neural elements not contained in the CNS, is called the
periperal nervous system (PNS).
The peripheral nervous system is composed of two branches. The first is the somatic nervous
system, which carries motor information from the CNS to the skeletal (voluntary) muscles via the
efferent nerves; and afferent nerves which carry sensory information from the muscles, joints,
skin, and bones back to the CNS
The other branch is called the autonomic nervous system (ANS), which carries information to
and from the glands, smooth muscles, and heart via the sympathetic and parasympathetic
subdivisions, and is involved in the regulation of homeostatic control.
Human Brain Anatomy
Viewed from the top, (superior view), it is evident that the brain is divided into two similar
parts, the left and right hemispheres. Running down the middle of the brain is the longitudinal
fissure, making the separation visible.
Below this fissure is a large tract of nerve fibers connecting the two hemispheres, called the
corpus callosum.
The outer portion of the brain, called the cerebral cortex or gray matter, as it lacks the white
myelin coating, is composed of a series of folded convolutions.
The elevated parts of the cortex are called gyri, and the depressions between the gyri are called
sulci. Gray matter contains mainly cell bodies and dendrites of the neurons.
Viewed from the lateral or side view, the cerebral cortex is divided into four separate areas, or
lobes; the occipital lobe, the parietal lobe, the frontal lobe and the temporal lobe.
The central sulcus separates the frontal lobe from the pariental lobe and the lateral sulcus
separates the temporal lobe from the parietal lobe.
A less evident separation exists between the parietal and occipital lobes.
Each of these lobes has a separate and unique function.
Lying just below the cortex is a thicker mass of brain tissue composed of myelinated fibers
having a whiter cast, appropriately called the white matter. Both gray matter and white matter
are also seen in the spinal cord.
Surrounding the brain is a composite of four tough membranes called the meninges, which
contain the jelly-like substance of the brain.
The meninges along with the bony skull, help to protect the brain from injury.
Cellular Elements of the Nervous System
The CNS is composed of nerve cells and associated cells.
The neurons can be considered the major working elements of the brain and spinal cord, despite
the fact that many other non-neural cell types are present. Each has a unique function, and the
proper functioning of each is a requirement for normal brain activity.
First, let us describe the non-neural elements of the brain.
Glia
Approximately half of the volume of the brain cavity is filled with a set of cells called glia. The
precise function of these elements is not completely known, but we do have some knowledge of a
few of the glial cell types. Glia act as a structural as well as functional units.
A
trocytes
star-shaped
regulate the ionic environment in which the neuronal elements reside.
Because precise ionic concentrations of K+ and Na+ in the fluids that bathe neurons are
necessary for normal activity, the astrocyte is an important cell.
may regulate blood flow to certain areas of the brain as neural activity is altered
Oligodendrocytes
produce the myelin sheath that wraps around the myelinated fibers.
in the periphery, the Schwann cells supply the axons with myelin
This is an extremely important function, as impairment in myelination results in severe
neuromuscular deficits.
In the disease multiple sclerosis, the insulating myelin becomes impaired, resulting in a severe
deficit in muscular control along with other neurological symptoms, such as alterations in
personality, memory loss, emotional instability, and pain. All these disorders may be traced to
the impairment of electrical conduction along the central neurons.
Vascular Cells
Most capillaries throughout the body are highly permeable, allowing most solutes to pass freely
across them into the interstitial space.
The capillaries of the brain are an exception. Oxygen, carbon dioxide and glucose may freely
cross the capillary membrane; however, many other bloodborne solutes that can easily cross other
capillaries are restricted in their movement across brain capillaries.
This limitation of the brain capillaries to the movement of certain solutes is called the bloodbrain barrier.
Adjacent endothelial cells of the brain capillaries are joined very tightly, forming what are called
tight junctions, so that solutes are unable to pass between adjacent cells.
In addition, astrocytes attach to the capillaries with foot-like processes.
This anatomical arrangement causes the capillary system of the brain to be less permeable to
bloodborne solutes than the other capillary networks of the body.
The blood-brain barrier serves to protect the brain from sudden changes in the environment
surrounding the neural elements.
This protection presents a serious problem, though, when physicians try to treat infections of the
brain.
Many drugs are unable to cross the blood-brain barrier and cannot reach the site of infection,
requiring the use of special drugs that are able to cross the blood-brain barrier.