# Structural Biochemistry/Cell Signaling Pathways/Nervous System

The nervous system is a network of specialized cells that coordinate the actions of an animal and send signals from one part of its body to another. These cells send signals either as electrochemical waves traveling along thin fibers called axons, or as chemicals released onto other cells. The nervous system is composed of neurons and other specialized cells called glial cells (plural form glia).
In most animals the nervous system consists of two parts, central and peripheral. The central nervous system contains the brain and spinal cord. The neurons of the central nervous system are interconnected in complex arrangements and transmit electrochemical signals from one to another. The peripheral nervous system consists of sensory neurons, clusters of neurons called ganglia, and nerves connecting them to each other and to the central nervous system. Sensory neurons are activated by inputs impinging on them from outside or inside the body, and send signals that inform the central nervous system of ongoing events. Motor neurons, situated either in the central nervous system or in peripheral ganglia, connect neurons to muscles or other effector organs. The interaction of the different neurons form neural circuits that regulate an organism's perception of the world and its body and behavior.
Nervous systems are found in most multicellular animals, but vary greatly in complexity. Sponges have no nervous system, although they have homologs of many genes that play crucial roles in nervous system function, and are capable of several whole-body responses, including a primitive form of locomotion. Radiata, including jellyfish, have a nervous system consisting of a simple nerve net. Bilaterian animals, which include the great majority of vertebrates and invertebrates, all have a nervous system containing a brain, spinal cord, and peripheral nerves.
A human nerve cell is composed of various components: the soma, or cell body (which has a nucleus), the axon (by which nerve signals travel), the myelin sheath, which provides conductivity and allows electrical signals to travel through nerve cells, dendrites, which receive signals from other nerve cells, and axon terminals, which nerve cells use to communicate with each other via the release and binding of neurotransmitters.
Neurons communicate with each other using neurotransmitters, which travel across synapses (the space between axon terminals of one nerve cell and the dendrites of another nerve cell) and bind to their appropriate receptors. However, inter cellular communication between nerve cells depends on action potentials, which are voltage differences across membranes. Action potentials are initiated by the movement of charged ions, such as potassium and sodium, across the cell membrane through voltage dependent ion gates. These gates are opened by binding of neurotransmitters to post-synaptic cells. Thus, when a neurotransmitter binds and causes the voltage dependent ion gates to open, ions flow across the membrane, causing a voltage difference which results in an action potential.
These action potentials travel along the axon, and axon terminals and dendrites allow these potentials to move through various nerve cells. Action potentials function on the all or nothing principle. In other words, if a particular stimuli or neurotransmitter concentration does not reach required levels, no action potential will occur. Thus, if a mosquito lands on your hand, you may not feel it because the pressure changed caused by the mosquito landing on you is not significant enough to generate an action potential. However, the pressure of, for example, a handshake, does, and therefore generates an action potential, causing you to feel the other hand. Under the all or nothing principle, action potentials either occur or they do not- an amplitude difference is irrelevant so long as the threshold for an action potential is reached. Instead, the varying feeling you get depends on the rate, or frequency, of action potentials. In other words, if someone threw a pencil at you, it would hurt less than if someone hit you with a car not because the amplitude of the action potential is higher when you are hit by a car, but because nerves are transmitting action potentials much faster.
The myelin sheath surrounding axons is critical to the propagation of action potentials. It essentially serves to maintain conductivity; without it, action potentials would travel much more slowly (so, for example, you would not be able to feel something hit you until after several seconds). This also improves efficiency and decreases the amount of energy required for nerve signaling. Multiple sclerosis is an example of disease caused by the degradation of the myelin sheath in nerve cells. The degradation of this sheath prevents nerve cells from communicating with each other by reducing the effect and velocity of action potentials. Because many important functions depend on a healthy nervous system, such as speech, movement, coordination, sensation, and vision, the degradation of the myelin sheaths can have a debilitating effect.

## Resting Potentials

All neurons exhibit a resting membrane potential which is the membrane potential of a resting neuron. Recall the definition of electricity, there is a voltage difference between the inside of the neuron and the extracellular space. The difference, resting potential, is usually about -70 mV between inside and outside of the neuron. However, the system then would want to equilibrate to 0 mV. Neurons use selective permeability to ions and the Na+/K+ ATPase to maintain a negative internal environment. The neuron also has a plasma membrane that is fairly impermeable to charged species. Ions are unlikely to cross the non-polar barrier, because it is energetically unfavorable. Inside the neuron, the concentration of potassium ion is high and concentration of sodium ion is low. Outside of the neuron has the opposite condition. The negative resting potential is generated by both permeability of the membrane to potassium ion compared with sodium ion. If potassium ion is more permeable and its concentration is higher inside, it will diffuse down its gradient out of the cell. In terms of charge movement, potassium ion is positively charged, so its movement out of the cell results in a cell interior that is negative. If we assume that the membrane starts at zero, and we take away a positive one, we end up with a negative one on the inside of the cell. Sodium ion cannot readily enter at rest, so the negative potential is maintained.
The Na+/K+ ATPase is important for restoring the gradient after action potentials have been fired. They transport three Na+ out of the cell for every two K+ into the cell at the expense of one ATP with a Na+/K+ pump. ATP is qualified as active transport. Each time the pump works, it results in the inside of the cell becoming relatively more negative, as two positive charges are moved in for every three that moved out.
Are neurons the only cells with the resting membrane potential? No. All cell have the resting membrane potential. Neurons and muscle tissues are unique in using the resting membrane potential to generate action potentials.
Modeling of the Resting Potential • Resting potential can be modeled by an artificial membrane that separates two chambers: --1. The concentration of KCl is higher in the inner chamber and lower in the outer chamber. --2. K+ diffuses down its gradient to the outer chamber. --3. Negative charge builds up in the inner chamber. • At equilibrium, both the electrical and chemical gradients are balanced. • The equilibrium potential (Eion) is the membrane voltage for a particular ion at equilibrium and can be calculated using the Nernst equation:
Eion = 62 mV (log[ion]outside/[ion]inside)
* The equilibrium potential of K+ (EK) is negative, while the equilibrium potential of Na+ (ENa) is positive. • In a resting neuron, the currents of K+ and Na+ are equal and opposite, and the resting potential across the membrane remains steady.

## Neurons, types of neurons, and supporting cells

Neurons are the cell of the nervous systems. Neurons carry electrical signals and communicate with each other via junction called synapse. Neurotransmitters, mainly hormones (epinephrine), are chemical that is released at synapse. Neurons uses membrane portention. The resting neuron membrane potential is -70mV. A neuron is composed of a soma - the cell body, and lots of dendrites. There are three types of neurons: Sensory neurons, interneurons, and motor neurons. Sensory Neurons are found in the Peripheral Nervous System. They communicate the signals from the external and internal environment to the Central Nervous System. Interneurons can only communicate between neurons. These are found in the Central Nervous System. Interneurons integrate signals and synapse with other neurons. Motor neurons carry out the signals from the Central Nervous System out to the effectors. Glial cells are supporting cells. Types of glial cells include astrocytes, oligodendrocytes, schwann cell, and myelination. Astrocytes are associated with capillary beds. It prevents capillary beds from leaking. It forms the barriers between the blood and the brain and there is great selectivity. Oligodendrocytes form insulating myelin sheath in the Central Nervous System. Schwann cells insulate myelin sheath associated with axon, it is found in the Peripheral Nervous System. Myelination wrap around axons and serves as electrical insulation. Multiple Sclerosis is a disorder caused by the deterioration of the myelin sheath.

## Action Potentials

Action potentials are a means of communicating between neurons. An action potential is started when the membrane is depolarized to a certain threshold. Action potentials are all or none, so depolarizations that do not meet the threshold do not do anything for the neuron. The threshold is a point when the charge is -55 mV. The resting potential of a neuron, which is the charge at equilibrium, is around -70 mV. The threshold is 15 mV above the resting potential, and only when the cell depolarizes to this point will the action potential initiate. The action potential starts when voltage gated sodium channels are activated. These channels allow an influx of sodium. Potassium channels also open up, which causes an efflux of potassium ions. The efflux of potassium ions causes the membrane to hyperpolarize (makes more negative) the cell. If the current of potassium exceeds the current of sodium, then the voltage of the cell returns to -70 mV, which is the resting potential. If the voltage increases past the threshold level, then the sodium current is larger than the potassium current. This induces a positive feedback, where more sodium channels are opened (slowly) from this effect, and even more sodium ions enter the cell. This sharp increase in the flow of sodium ions causes the cell to depolarize rapidly, which results in the cell “firing”, which produces an action potential. The rapid depolarization is ended when the sodium channels open all the way. This causes the membrane voltage to reach a maximum. The voltage shuts the sodium channels off, and the channels are inactivated. At the same time, the voltage opens voltage gated potassium channels. The result of these two actions is the repolarization of the membrane. As potassium ions leak out and sodium channels can no longer diffuse across the membrane, the cell is brought to its equilibrium potential.

## Various phase of the action potential

An action potential consists of various phases. (1) At the resting potential, voltage-gated sodium channels are closed. Some potassium channels are open, but most voltage-gated potassium channels are closed. (2) When the membrane depolarizes, some voltage-gated sodium channels open, allowing the influx of sodium ions. The sodium ion influx causes further depolarization, which more voltage-gated sodium channels will open, causing more sodium ions to flow in. (3) Once threshold is reached, an action potential will occur. The positive-feedback cycles of opening of sodium channels depolarize the membrane rapidly (4) Voltage-gated sodium channels will inactive after opening, stopping the influx of sodium ions. Voltage-gated potassium channels will open and potassium ions will flow out. (5) The gated potassium channels eventually close, and the membrane potential returns to the resting potential. (6) The refractory period is a result of the closing of the sodium channels, which cannot be opened again until the refractory period is over.

## Postsynaptic Potentials

Information transmitting occurs at the synapses. There are two types of synapses - Electrical synapses and Chemical synapses. At the electrical synapses, the electric current flows from one neuron to another neuron through gap junction. At the chemical synapses, chemical neurotransmitter carries the information through the synaptic cleft.

## Central Nervous System

The central nervous system consists of the brain and the spinal cord. The spinal cord is a long nervous tissue that extends along the vertebral column from the head to the lower back. It is composed of many distinct structures working together to coordinate the body. The most important is the brain, which has several components:
The cerebrum is the largest portion of the brain and it controls consciousness. It is in control of voluntary movement, sensory perception, speech, memory, and creative thought.
The cerebellum helps to fine-tune voluntary movement, but is not directly involved in it. It makes sure that movements are coordinated and balanced.
The brainstem is a part of the medulla oblongata and is responsible for the control and regulation of involuntary functions. These functions include breathing, cardiovascular regulation, and swallowing. The medulla oblongata is needed to sustain life and processes a great deal of information.
The hypothalamus is the source of posterior pituitary hormones and releasing hormones acting on the anterior pituitary. It is also responsible for homeostasis maintenance, which includes regulation of temperature, hunger, thirst, water balance, generation of emotion, as well as roles in sexual and mating behaviors.
Brain
It is responsible for integration of sensory information, coordination of motor movement, and cognition. The myelination that we saw around axon is also present in the brain. Its presence allows us to distinguish between gray matter, which is unmyelinated, and white matter. The brain of all vertebrates develops from dividing it into the forebrain, the mid-brain, and the hindbrain.
-Forebrain is the most recently acquired part of the CNS in terms of evolutionary development. It is further broken down into the telencephalon and diencephalon. Telencephalon consists of a pair of large left and right hemispheres that can be further sectioned into the frontal, parietal, occipital and temporal lobes. A group of structures located deep with the cerebrum that makes up the diencephalon. A large portion of the diencephalon is the cerebral cortex, a region of highly convoluted gray matter that can be seen on the surface of the brain. The cortex is responsible for the highest-level functioning in the nervous system, including creative thought and future planning. It also integrates sensory information and controls movement. Each hemisphere is independent, however, they do communicate through a large connection called the corpus collosum.
-Midbrain serves as a relay point between more peripheral structures and the forebrain. It passes sensory and visual information to the forebrain, while receiving motor instructions from the forebrain and passing them to the hindbrain.
-The hindbrain contains three “main structures” that are medulla oblongata, pons, and cerebellum. Together, they make the brainstem. Medulla oblongata is the most highly conserved part of the brain that is responsible for modulating ventilation rate, heart rate, and gastrointestinal rate. “The pons seems to serve as a relay station carrying signals from various parts of the cerebral cortex and cerebellum. The pons also participates in the reflexes that regulate breathing.” The cerebellum is a quality control agent that checks the motor signal sent from the cortex is in agreement with the sensory information coming from the body. It is what prevents us from falling over when we trip. It rapidly realizes that the motor signal to take a step was not successfully carried out, as we tripped. Instead of letting us fall on our faces, the cerebellum helps the cortex to adjust to the new situation so that we catch ourselves.
The Spinal Cord
The spinal cord is divided into 4 distinct regions. These distinct regions in the spinal cord organize neurons segmentally. Within a single segment, neurons are grouped and located according to their function throughout the rest of the body. These four segments are the cervical region (8 segments), thoracic region (12 segments), lumbar region (5 segments), and the sacral region (5 segments). Each region is responsible for different parts of the human body. For example, the cervical region is responsible for controlling the arms and the lumbar region is responsible for controlling the legs. Axons usually enter the nerves near each segment in this innervated structure (e.g. fibers that innervate the arm run in the cervical spinal nerves while fibers that innervate the leg run in the lumbosacral spinal nerves). Sensory and motor neurons lie in separate portions of the spinal cord. In general, cells in the dorsal spinal cord and axons in the dorsal spinal nerves serve an afferent function (sensory fibers), while the cells in the ventral spinal cord and axons in the ventral spinal nerves serve as motor in function (efferent fibers). In specific, however, position of ascending pathways carrying fine touch, pressure, and information about the position of muscles and joints are found in the dorsal and lateral columns of each spinal segment. The dorsal column pathway runs on the same side of the spinal cord and crosses at the brain stem, goes through the medial lemniscus, and travels to the cerebral cortex. The position of fibers carrying pain information and pressure information are found in the anterolateral pathway. Information is carried in contralateral anterolateral tracts: the spinothalamic and spinoreticular tracts. Spinoreticular tract ends in the brain stem while spinothalamic tract ends in the thalamus. The anterolateral pathway crosses at the spinal cord and travels to the cerebral cortex. For motor information (efferent information), positions of descending fibers are found in the dorsolateral and ventromedial columns.
The Peripheral Nervous System
This system consists of a sensory system that carries information from the senses to the central nervous and then back to the body. Vertebrate PNS structurally consist of left and right pairs of cranial and spinal nerves and associated ganglia. The cranial nerves start from the brain and end mostly in organs of the head and upper body. The spinal nerves start in the spinal cord and spreads into parts of the body below the head. It also consists of a motor system that branches out from the central nervous system, so it targets certain muscles or organs. The motor system can be divided into the somatic system and the autonomic system.
The Somatic Nervous System
The somatic nervous system is responsible for voluntary movement. We described the interface between the neuron and muscle as the neuromuscular junction. Release of acetylcholine fom the nerve terminal onto the muscle leads to contraction. The acetylcholine binding to its receptor on the muscle ultimately leads to muscle depolarization. The somatic nervous system is also responsible for providing us with reflexes, which are automatic. They do not require input or integration from the brain o function. There are two types of reflex arcs: monosynaptic and polysynaptic. Reflexes usually serve a protective purpose. For example, we’d pull our hand away from a hot stove before our brain processes that it is hot.
-Monosynaptic
In a monosynaptic reflex arc, there is a single synapse between the sensory neuron that received the information and the motor neuron that responds. An example will be the knee jerk reflex. When the patellar tendon is stretched, information travels up the sensory neuron to the spinal cord, where it interfaces with the motor neuron to contract the quadriceps muscle. The net result is a straightening of the leg, which lessens the tension to the patellar tendon. However, this reflex is responding to a potentially dangerous situation. If the patellar tendon is stretched too far, it may tear, damaging the knee joint. This reflex helps to protect us.
-Polysynaptic
In a polysynaptic reflex arc, there is at least one interneuron between the sensory and motor neuron. An example will be your reaction to stepping on a tack, which involves the withdrawal reflex. The foot that steps on the tack will be simulated to jerk up (monosynaptic reflex). However, if we are to maintain our balance, we need out other foot to go down and plant itself on the ground. For this to occur, the motor neuron that controls the opposite leg must to be stimulated. Interneuron in the spinal cord provide the connection from the incoming sensory information on the leg being jerked up to the motor neuron for the supporting leg.
On the other hand, the autonomic system controls tissues other than skeletal muscles, such as cardiac muscle, glands, and organs. This system controls processes that are involuntary, such as heartbeat, movements in the digestive tract, and contraction of the bladder. Autonomic neurons are able to either excite or inhibit target muscles or organs. This nervous system is subdivided into sympathetic division and parasympathetic division. These 2 systems work antagonistically and usually have opposite effects.
The Autonomic Nervous System
The autonomic nervous system is a part of the peripheral nervous system that controls visceral functions. The autonomic nervous system affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils, urination, and sexual arousal. Although most of this system's actions are voluntary, some actions, such as breathing, are involuntary. The autonomic nervous system is divided into the sympathetic nervous system and the parasympathetic nervous system. These two subsystems work together to produce homeostasis. Both subsystems are made up of a two-neuron chain between the central nervous system and the peripheral nervous system.
In the sympathetic and parasympathetic nervous systems, pre-ganglionic neurons are in the central nervous system, but they synapse to post-ganglionic neurons in the peripheral nervous system. These post-ganglionic neurons will then synapse to the target cells.
In the sympathetic nervous system, the preganglionic transmitter is acetylcholine, and they bind to nicotinic cholinergic receptors on post-ganglionic cells. Post-ganglionic cells transmit nor-epinephrine, which bind to adrenergic receptors on target cells. The parasympathetic nervous system releases acetylcholine as well as the pre-ganglionic transmitter, and bind to nicotinic cholinergic receptors on post-ganglionic cells. The transmitter from these cells is acetylcholine, and they bind to muscarinic cholinergic receptors on target cells.
Increased activity in the sympathetic nervous system includes increase of heart rate, increase in blood pressure of smooth muscles, and decrease of gut motility. Parasympathetic activity decrease heart rate and increases gut motility.
Reflex Arcs
Occurs when a signal from the peripheral nervous system travels straight to another site in the body, triggering an involuntary reaction with the signal entering the central nervous system and traveling to the brain for processing before a reply signal is sent back. This results in a much faster reaction time and is typically used in situations where bodily harm is imminent.
Sympathetic Nervous System
The sympathetic nervous system controls the body's resources under stress, otherwise known as the fight-or-flight response. However, the sympathetic nervous system is constantly active in order to maintain homeostasis. An example would be that when heart beats faster, the liver would convert glycogen to glucose, bronchi of the lungs would expand to support increased gas exchange.
Examples of sympathetic system action. :
| Organ | Effect |
| Eye | Dilates pupil |
| Heart | Increases rate and force of contraction |
| Lungs | Dilates bronchioles |
| Digestive tract | Inhibits peristalsis |
| Kidney | Increases renin production |
| Penis | Promotes ejaculation |
Parasympathetic Nervous System
The parasympathetic nervous system controls activities that occur when the body is at rest such as salivation, lacrimation, urination, digestion, and defecation. It's actions are often described as "rest and digest." It works in conjunction with the sympathetic nervous system to maintain homeostasis in the body. An example would be the increase activity in parasympathetic division decreases heart rate would increase glycogen production and enhance digestion.
Examples of parasympathetic system action. :
| Organ | Effect |
| Eye | Constricts pupil |
| Heart | Decreases rate and force of contraction |
| Liver | Glycogen synthesis |
| Digestive system | Increases activity |
| Kidney | Increases urine production |
| Tear Glands | Secretion |
What is Mental Inertia and what causes this symptom. It is the involuntary or the unwillingness to perform something. In the other hands, we can say it is slacking in people’s mind to think of something or come up with a plan. People usually call that in a normal way is laziness that is hidden somewhere inside each of us. And based on each person’s function, it will display different level of the laziness. Therefore, the immunity is also different. So when we can break this slacking and laziness, we can create the impulse. There are many types that that cause by mental inertia: - By incorrectly established result - By adherence to a faulty technique - By the incorrect understanding of mechanism of action - By improper controls Now we know what causes this symptom so we can find a way to overcome it. Here is just an example of how to overcome it. There are several ways to handle it. By mentally, try to see the result of our action and capture it. Then we will start moving to physically and let our brains follow the suit. We just try to start very slow to see the actual result from the small step. The most important thing is just believe in ourselves that we can do everything. It is very easy to break and control once we know how to overcome it.

## Nervous system disorders

Depression is a disorder characterized by depression mood, for example, appetite, sleep and energy level. There are two forms of depressive illness: major depressive disorder and bipolar disorder. Major depressive disorder maybe last many months with no pleasure and no interest. Bipolar disorder involves swings of mood form high to low and affects very rarely to people.
Schizophrenia is a very rare yet severe mental disturbance characterized by psychotic episodes in which patients have a distorted perception of reality. People with this illness usually suffer from hallucination and delusions.
Alzheimer’s disease is a mental deterioration, or dementia characterized by confusion and many other symptoms. This disease is progressive, with patients gradually becoming less able to function. The disease is mainly associated with the development of senility as a result of a buildup in β-amyloid plaques. However, the causes for the disease are not only genetically related, but they can stem from any damage to the axonal transport system which itself might arise from structural changes or even traumatic brain injury. The resulting damage incurred into the axonal transport system has the potential for vesicles containing chemical precursors to build up and create damaging plaques, as is the case with Alzheimer’s disease. Various other defects in axonal transport systems or mutations in gene coding can cause this neurodegenerative disorder. Which could lead to the death of neurons in many areas of the brain.
Parkinson’s disease is characterized by difficulty in initiating movement and slowness of movement. Its symptoms result from the death of neurons in the midbrain. At present, there is no cure for Parkinson’s disease.

## References

http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CNS.html#SpinalCord
http://www.emc.maricopa.edu/faculty/farabee/BIOBK/BioBookNERV.html#Central Nervous System
Gorazd B. Stokin and Lawrence S.B. Goldstein, "Axonal Transport and Alzheimer's Disease". Annual Review of Biochemistry Vol. 75: 607-627 (Volume publication date July 2006) Print