GENERAL DESIGN OF THE NERVOUS SYSTEM
- The central nervous system contains more than 100 billion neurons.
- Incoming signals enter the neuron through synapses located mostly on the neuronal dendrites, but also on the cell body.
- For different types of neurons, there may be only a few hundred or as many as 200,000 such synaptic connections from input fibers.
- A special feature of most synapses is that the signal normally passes only in the forward direction, from the axon of a preceding neuron to dendrites on cell membranes of subsequent neurons. This feature forces the signal to travel in required directions to perform specific nervous functions.
SENSORY PART OF THE NERVOUS
SYSTEM SENSORY RECEPTORS
Most activities of the nervous system are initiated by sensory receptors.
MOTOR PART OF THE NERVOUS
The most important eventual role of the nervous system is to control the various bodily activities. This task is
achieved by controlling
(1) contraction of appropriate
skeletal muscles throughout the body,
(2) contraction of
smooth muscle in the internal organs, and
of active chemical substances by both exocrine and endocrine glands in many parts of the body.
These activities are collectively called motor functions of the nervous system and the muscles and glands are called effectors because they are the actual anatomical structures that perform the functions dictated by the nerve signals
FUNCTION OF THE NERVOUS SYSTEM
One of the most important functions of the nervous system is to process incoming information in such a way that appropriate mental and motor responses will occur. More than 99 percent of all sensory information is discarded by the brain as irrelevant and unimportant.
For instance, one is ordinarily unaware of the parts of the body that is in contact with clothing, as well as of the seat pressure when sitting. when important sensory information excites the mind, it is immediately channeled into proper integrative and motor regions of the brain to cause desired responses. This channeling and processing of information are called the integrative function of the nervous system.
ROLE OF SYNAPSES
IN PROCESSING INFORMATION
The synapse is the junction point from one neuron to the next. synapses determine the directions that
the nervous signals will spread through the nervous system. Some synapses transmit signals from one neuron
to the next with ease, whereas others transmit signals only with difficulty. Also, facilitatory and inhibitory signals from other areas in the nervous system can control synaptic transmission, sometimes opening the synapses for transmission and at other times closing them. In addition, some postsynaptic neurons respond with large numbers of output impulses, and others respond with only a few.
STORAGE OF INFORMATION MEMORY
Only a small fraction of even the most important sensory information usually causes an immediate motor response.
However, much of the information is stored for future control of motor activities and for use in the thinking
processes. Most storage occurs in the cerebral cortex, but even the basal regions of the brain and the spinal cord can
store small amounts of information. The storage of information is the process we call memory, and this, too, is a function of the synapses. Each time certain types of sensory signals pass-through sequences of synapses, these synapses become more capable of transmitting the same type of signal the next time, a process called facilitation. After the sensory signals have passed through the synapses a large number of times, the synapses become so facilitated that signals generated within the brain itself can also cause transmission of impulses through the same sequences of synapses, even when the sensory input is not excited. This process gives the person a perception of experiencing the original sensations, although the perceptions are only memories of the sensations.
Once memories have been stored in the nervous system, they become part of the brain processing mechanism for future “thinking.” That is, the thinking processes of the brain compare new sensory experiences with stored
memories; the memories then help to select the important new sensory information and to channel this into appropriate memory storage areas for future use or into motor areas to cause immediate bodily responses.
MAJOR LEVELS OF CENTRAL NERVOUS SYSTEM FUNCTION
Three major levels of the central nervous system have specific functional characteristics:
(1) the spinal cord level, (2) the lower brain or subcortical level, and (3) the higher brain or cortical level.
SPINAL CORD LEVEL:
Apart from channeling signals from periphery of the body to brain, many highly organized spinal cord functions also occur. For instance, neuronal circuits in the cord can caused (1) walking movements, (2) reflexes that withdraw portions of the body from painful objects, (3) reflexes that stiffen the legs to support the body against gravity, and
(4) reflexes that control local blood vessels, gastrointestinal movements, or urinary excretion. In fact, the upper
levels of the nervous system often operate not by sending signals directly to the periphery of the body but by sending
signals to the control centers of the cord, simply “commanding” the cord centers to perform their functions.
LOWER BRAIN OR SUBCORTICAL LEVEL
Many, if not most, of what we call subconscious activities of the body are controlled in the lower areas of the
a brain that is, in the medulla, pons, mesencephalon, hypothalamus, thalamus, cerebellum, and basal ganglia.
For instance, subconscious control of arterial pressure and respiration is achieved mainly in the medulla and
pons. Control of equilibrium is a combined function of the older portions of the cerebellum and the reticular
substance of the medulla, pons, and mesencephalon. Feeding reflexes, such as salivation and licking of the lips
in response to the taste of food, are controlled by areas in the medulla, pons, mesencephalon, amygdala, and hypothalamus. In addition, many emotional patterns such as anger, excitement, sexual response, reaction to pain,
and reaction to pleasure can still occur after the destruction of much of the cerebral cortex.
HIGHER BRAIN OR CORTICAL LEVEL
The cerebral cortex is an extremely large memory storehouse. The cortex never functions alone but
always in association with the lower centers of the nervous system. Without the cerebral cortex, the functions of the lower brain centers are often imprecise. The vast storehouse of cortical information usually converts these functions to
determinative and precise operations. Finally, the cerebral cortex is essential for most of our thought processes, but it cannot function by itself. In fact, it is the lower brain centers, not the cortex, that initiate wakefulness in the cerebral cortex, thus opening its bank of memories to the thinking machinery of the brain. Thus, each portion of the nervous system performs specific functions, but it is the cortex that opens a world of stored information for use by the mind.
CENTRAL NERVOUS SYSTEM SYNAPSES:
Information is transmitted in the central nervous system mainly in the form of nerve impulses, through a succession of neurons, one after another. However, in addition, each impulse (1) may be blocked in its transmission from one neuron to the next (2) may be changed from a single impulse into repetitive impulses, or (3) may be integrated with impulses from other neurons to cause highly intricate patterns of impulses in successive neurons. All these functions can
be classified as synaptic functions of neurons.
There are two major types of synapses
(1) chemical and (2) electrical.
In chemical synapses, the first neuron secretes at its nerve ending synapse a chemical substance called a
neurotransmitter (often called a transmitter substance), and this transmitter in turn acts on receptor proteins
in the membrane of the next neuron to excite the neuron, inhibit it, or modify its sensitivity in some other way. More than 40 important neurotransmitters have been discovered thus far. Some of the best known are acetylcholine, norepinephrine, epinephrine, histamine, gamma-aminobutyric acid (GABA), glycine, serotonin, and glutamate.
In electrical synapses, the cytoplasms of adjacent cells are directly connected by clusters of ion channels called
gap junctions that allow free movement of ions from the interior of one cell to the interior of the next cell.
Most synapses in the brain are chemical, electrical, and chemical synapses that may coexist and interact in the central nervous system. The bidirectional transmission of electrical synapses permits them to help coordinate the activities of large groups of interconnected neurons.
“One-Way” Conduction at Chemical Synapses:
Chemical synapses is always transmit the signals in one direction that is, from the neuron that secretes the neurotransmitter, called the presynaptic neuron, to the neuron on which the transmitter acts, called the postsynaptic neuron. This phenomenon is the principle of one-way conduction at chemical synapses, and it is quite different from conduction through electrical synapses, which often transmit signals in either direction.
PHYSIOLOGICAL ANATOMY OF THE SYNAPSE
Fig shows a typical anterior motor neuron in the anterior horn of the spinal cord. It is composed of three
major parts: the soma, which is the main body of the neuron; a single axon, which extends from the soma into
a peripheral nerve that leaves the spinal cord; and the dendrites, which are great numbers of branching projections of the soma that extend as much as 1 millimeter into the surrounding areas of the cord.
As many as 10,000 to 200,000 minute synaptic knobs called presynaptic terminals lie on the surfaces of the
dendrites and soma of the motor neuron, with about 80 to 95 percent of them on the dendrites and only 5
to 20 percent on the soma. These presynaptic terminals are the ends of nerve fibrils that originate from many
other neurons. Many of these presynaptic terminals are excitatory that is, they secrete a neurotransmitter that
excites the postsynaptic neuron. However, other presynaptic terminals are inhibitory that is, they secrete a neurotransmitter that inhibits the postsynaptic neuron.
Neurons in other parts of the cord and brain differ from the anterior motor neuron in
(1) the size of the cell body; (2) the length, size, and number of dendrites,
ranging in length from almost zero to many centimeters; (3) the length and size of the axon; and (4) the number of
presynaptic terminals, which may range from only a few to as many as 200,000. These differences make neurons
in different parts of the nervous system react differently to incoming synaptic signals and, therefore, perform
many different functions.
Presynaptic Terminals: They have varied anatomical forms, but most of them resemble small round or oval knobs and, therefore, are sometimes called terminal knobs, boutons, end-feet. The presynaptic terminal is separated from the postsynaptic neuronal soma by a synaptic cleft having a width usually of 200 to 300 angstroms.
The terminal has two internal structures important to the excitatory or inhibitory function of the synapse: the transmitter vesicles and the mitochondria.
The transmitter vesicles contain the neurotransmitter that, when released into the synaptic cleft, either
excites or inhibits the postsynaptic neuron. It excites the postsynaptic neuron if the neuronal membrane contains
excitatory receptors, and it inhibits the neuron if the membrane contains inhibitory receptors. The mitochondria ATP, which in turn supplies the energy for synthesizing new transmitter substances.
The mechanism by Which an Action Potential Causes Transmitter Release from
the Presynaptic Terminals—Role of Calcium Ions
the presynaptic membrane contains large numbers of voltage-gated calcium channels. When an action potential
depolarizes the presynaptic membrane, these calcium channels open and allow large numbers of calcium ions
to flow into the terminal. The quantity of neurotransmitters that are then released from the terminal into the synaptic cleft is directly related to the number of calcium ions that enter.
when the calcium ions enter the presynaptic terminal, they bind with special protein molecules on the inside
the surface of the presynaptic membrane called release sites. This binding, in turn, causes the release sites to open
through the membrane, allowing a few transmitter vesicles to release their transmitter into the cleft after each
single action potential. For the vesicles that store the the neurotransmitter acetylcholine, between 2000 and 10,000
molecules of acetylcholine are present in each vesicle, and there are enough vesicles in the presynaptic terminal to
transmit from a few hundred to more than 10,000 action potentials.
The action of the Transmitter Substance on the Postsynaptic Neuron—Function
of “Receptor Proteins”
The molecules of postsynaptic receptors have two important components:
(1) a binding component that protrudes
outward form the membrane into the synaptic cleft, where it binds the neurotransmitter coming from the presynaptic terminal, and
(2) an intracellular component that passes all the way through the postsynaptic membrane to the interior of the postsynaptic neuron.
Receptor activation controls the opening of ion channels in the postsynaptic cell in one of two ways:
(1) by gating ion channels directly and allowing passage of specified types
of ions through the membrane, or
(2) by activating a “second messenger” that is not an ion channel but instead
is a molecule that protrudes into the cell cytoplasm and activates one or more substances inside the postsynaptic
neuron. These second messengers increase or decrease specific cellular functions.
Neurotransmitter receptors that directly gate ion channels are often called ionotropic receptors, whereas
those that act through second messenger systems are called metabotropic receptors.
Ion Channels. The ion channels in the postsynaptic neuronal membrane are usually of two types: (1) cation
channels that most often allow sodium ions to pass when opened but sometimes also allow potassium and/or
calcium ions to pass, and (2) anion channels that mainly allow chloride ions to pass but allow minute quantities of
other anions to pass as well.
The cation channels that conduct sodium ions are lined with negative charges. These charges attract the
positively charged sodium ions into the channel when the channel diameter increases to a size larger than that
of the hydrated sodium ion. However, those same negative charges repel chloride ions and other anions and
prevent their passage.
The anion channels, when the channel diameters become large enough, chloride ions pass into the channels
and on through to the opposite side, whereas sodium, potassium, and calcium cations are blocked, mainly
because their hydrated ions are too large to pass.
A neurotransmitter that opens cation channels is called an excitatory transmitter. Conversely, opening anion channels allows negative electrical charges to enter, which inhibits the neuron. Therefore, neurotransmitters that open these channels are called inhibitory transmitters.
“Second Messenger” System in the Postsynaptic
In many instances, prolonged postsynaptic neuronal excitation or inhibition is achieved by activating a
“second messenger” chemical system inside the postsynaptic neuronal cell itself, and then it is the second messenger that causes the prolonged effect.
There are several types of second messenger systems. One of the most common types uses a group of proteins
called G proteins. Figure shows a membrane receptor G protein. The inactive G protein complex is free in
the cytosol and consists of GDP plus three components: an alpha (α) component that is the activator portion of the G protein, and beta (β) and gamma (γ) components that are attached to the alpha component. As long as the G protein complex is bound to GDP, it remains inactive. When the receptor is activated by a neurotransmitter, following a nerve impulse, the receptor undergoes a conformational change, exposing a binding site for the G protein complex, which then binds to the portion of the receptor that protrudes into the interior of the cell. This process permits the α subunit to release GDP and simultaneously bind guanosine triphosphate (GTP) while separating from the β and γ portions of the complex. The separated α-GTP complex is then free to move within the cytoplasm of the cell and perform one or more of multiple functions, depending on the specific characteristic of each type of neuron.
The following four changes that can occur are shown
- Opening specific ion channels through the postsynaptic cell membrane. potassium channel that is opened in response to the G protein; this channel often stays open for a prolonged time, in contrast to rapid closure of directly activated ion channels that do not use the second messenger system.
- Activation of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP) in the neuronal cell.
- Activation of one or more intracellular enzymes. The G protein can directly activate one or more intracellular enzymes. In turn, the enzymes can cause any one of many specific chemical functions in the cell.
- Activation of gene transcription. Activation of gene transcription is one of the most important effects of activation of the second messenger systems because gene transcription can cause the formation of new proteins within the neuron, thereby changing its metabolic machinery or its structure.
Inactivation of the G protein occurs when the GTP bound to the α subunit is hydrolyzed to GDP. This action
causes the α subunit to release from its target protein, thereby inactivating the second messenger systems, and
then to combine again with the β and γ subunits, returning the G protein complex to its inactive state.
Excitatory or Inhibitory Receptors in the Postsynaptic Membrane
The different molecular and membrane mechanisms
used by the different receptors to cause excitation or inhibition include the following.
- Opening of sodium channels to allow large numbers of positive electrical charges to flow to the interior of the postsynaptic cell. This action raises the intracellular membrane potential in the positive direction up toward the threshold level for excitation.
- Depressed conduction through chloride or potassium channels, or both. This action decreases the
diffusion of negatively charged chloride ions to the inside of the postsynaptic neuron or decreases
the diffusion of positively charged potassium ions to the outside.
- Various changes in the internal metabolism of the postsynaptic neuron excite cell activity
- Opening of chloride ion channels through the postsynaptic neuronal membrane. This action allows
the rapid diffusion of negatively charged chloride ions from outside the postsynaptic neuron to the
- Increase in conductance of potassium ions out of the neuron. This action allows positive ions to diffuse
to the exterior, which causes increased negativity inside the neuron; this is inhibitory.
- Activation of receptor enzymes that inhibit cellular metabolic functions that increase the number
of inhibitory synaptic receptors or decrease the number of excitatory receptors.
Small-Molecule, Rapidly Acting Transmitters
In most cases, the small-molecule types of transmitters are synthesized in the cytosol of the presynaptic terminal
and are absorbed by means of active transport into the many transmitter vesicles in the terminal. Then, each
time an action potential reaches the presynaptic terminal, a few vesicles at a time release their transmitter into
the synaptic cleft. This action usually occurs within a millisecond or less by the mechanism described earlier.
Recycling of the Small-Molecule Types of Vesicles.
Vesicles that store and release small-molecule transmitters are continually recycled and used over and over
again. After they fuse with the synaptic membrane and open to release their transmitter substance, the vesicle
membrane at first simply becomes part of the synaptic membrane. However, within seconds to minutes, the
vesicle portion of the membrane invaginates back to the inside of the presynaptic terminal and pinches off to
form a new vesicle. The new vesicular membrane still contains appropriate enzyme proteins or transport proteins required for synthesizing and/or concentrating new transmitter substance inside the vesicle.
Acetylcholine is a typical small-molecule transmitter that obeys the principles of synthesis and releases stated
Characteristics of Some Important Small-Molecule Transmitters
Acetylcholine is secreted by neurons in many areas of the nervous system but specifically by
(1) the terminals of the large pyramidal cells from the motor cortex, (2) several different types of neurons in the basal ganglia, (3) the motor neurons that innervate the skeletal muscles, (4) the preganglionic neurons of the
the autonomic nervous system, (5) the postganglionic neurons of the parasympathetic nervous system, and (6) some of
the postganglionic neurons of the sympathetic nervous system. In most instances, acetylcholine has an excitatory
effect; however, it is known to have inhibitory effects at some peripheral parasympathetic nerve endings, such as
inhibition of the heart by the vagus nerves.
Norepinephrine is secreted by the terminals of many neurons whose cell bodies are located in the brain stem
and hypothalamus. Specifically, norepinephrine-secreting neurons located in the locus ceruleus in the pons send
nerve fibers to widespread areas of the brain to help control overall activity and mood of the mind. Norepinephrine is also secreted by most postganglionic neurons of the sympathetic nervous system, where it
excites some organs but inhibits others.
Dopamine is secreted by neurons that originate in the substantia nigra. The termination of these neurons is
mainly in the striatal region of the basal ganglia. The effect of dopamine is usually inhibition.
Glycine is secreted mainly at synapses in the spinal
cord. It is believed to always act as an inhibitory transmitter.
GABA (gamma-aminobutyric acid) is secreted by nerve terminals in the spinal cord, cerebellum, basal
ganglia, and many areas of the cortex. It is believed to always cause inhibition.
Glutamate is secreted by the presynaptic terminals in many of the sensory pathways entering the central nervous
system, as well as in many areas of the cerebral cortex. It probably always causes excitation.
Serotonin is secreted by nuclei that originate in the median raphe of the brain stem and project to many brain
and spinal cord areas, especially to the dorsal horns of the spinal cord and to the hypothalamus. Serotonin acts as an inhibitor of pain pathways in the cord, and an inhibitor action in the higher regions of the nervous system is
believed to help control the mood of the person, perhapseven to cause sleep.
Nitric oxide is especially secreted by nerve terminals in areas of the brain responsible for long-term behavior and memory. Nitric oxide is different from other small-molecule transmitters in its mechanism of formation in the presynaptic terminal and in its actions on the postsynaptic neuron. It is not preformed and stored in vesicles in the presynaptic terminal as are other transmitters. Instead, it is synthesized almost instantly as needed and then diffuses out of the presynaptic terminals over a period of seconds rather than being released in vesicular packets. Next, it diffuses into postsynaptic neurons nearby. In the postsynaptic neuron, it usually does not greatly alter the membrane
potential but instead changes intracellular metabolic functions that modify neuronal excitability for seconds,
minutes, or perhaps even longer.
The neuropeptides are not synthesized in the cytosol of the presynaptic terminals. Instead, they are synthesized as
integral parts of large-protein molecules by ribosomes in the neuronal cell body.
The protein molecules then enter the spaces inside the endoplasmic reticulum of the cell body and subsequently
inside the Golgi apparatus, where two changes occur: First, the neuropeptide-forming protein is enzymatically
split into smaller fragments, some of which are either the neuropeptide itself or a precursor of it. Second, the Golgi
apparatus packages the neuropeptide into minute transmitter vesicles that are released into the cytoplasm. Then the transmitter vesicles are transported all the way to the tips of the nerve fibers by axonal streaming of the axon
cytoplasm, traveling at the slow rate of only a few centimeters per day. Finally, these vesicles release their transmitter at the neuronal terminals in response to action potentials in the same manner as for small-molecule transmitters. However, the vesicle is autolyzed and is not reused.
neuropeptides cause much more prolonged actions. Some of these actions include prolonged closure of calcium channels, prolonged changes in the metabolic machinery of cells, prolonged changes inactivation or
deactivation of specific genes in the cell nucleus, or prolonged alterations in numbers of excitatory or inhibitory receptors. Some of these effects last for days, but others last perhaps for months or years