My note about nervous system

My Note about nervous system

By : Nanda E.S Sejati

We will show them Our signs in the horizons and within themselves until it becomes clear to them that it is the truth. But is it not sufficient concerning your Lord that He is, over all things, a Witness?

(Fushilat : 53)

Nervous system is amazing system in our body (actually all of our body system is amazing but nervous system is special).  they just have mass about 2 kg, or 3 % in our body, but they control of all body component to work well. They control how our heart to pump the blood, how we maintain our breath, how we move, and so many others. Small damage on them can result imbalance in our body. And our life will not the be the same again.

Nervous system are created by connection between one neuron and others neuron, its really complex. We have approximately 100 billion of neuron in the brain and 100 million neuron in spinal cord.  Neuron is the smallest stuctural and functional unit of nervous. So nervous and neuron is different. Neuron is nervous cell. Neuron is special cells because they can remember (so do lymphocyt, but they more complex and perfect), saving information for many years, and create a integrative “film” from puzzle of infomation, simple example of this is imagination and dream.

Neuron, like other cell, to support their function they need some organels. They are nucleus, ribosom, renticulum endoplasma, mitochondrion, microfibrils (in neuron called neurofibrils), microtubules, and lysosome.

Endoplasmic reticulum that bind ribosom (rough endoplasmic reticulum) in neuron is called Nissl Bodies. So because nissl bodies contain ribosom, they role in protein synthesis that needed neuron to maintain their life. Microfibril/Neurofibril act as cytoskeleton for neuron, it give neuron shape. Microtubule assist moving material between axon and cell body.

Most neuron have three main part, they are Cell Body, Axon, and Dendrites. Cells body also known as perykarion or soma, which contain nucleus. Axon is structure that have function like a “way” for impulse to transmit between one neuron and others. An Axon is thin, cylindrical projection, but the part of axon that join with cell body become more bigger in the proximal part, and make structure like “cone” called axon hillock. Axoplasm is a fluid/cytoplasm in axon, an axon will surrounded by a plasm membrane called axolemma. Axon can also has branch, this branch is called axon collateral . Axon is covered by schwan cells. And between axolemma and schwan cell contain multilayered lipid and protein covering the axon called myelin sheath. Axon, which covered by myelin sheath are called myelinated and axon whic uncovered with myelin sheath are called unmyelinated. Axon then will terminante in Axon terminal . Dendrites is structure like “tree without leave” that spread from cell body, their function mainly is receive “impulse” from other neuron (from axon terminal of other neuron). Impuls is a action potential from stimulus that transmitted from one neuron to others ( I will elaborate it later). Actually one neuron with other neuron not really connected (axon terminal bind with dendrites), instead there are a gap between one neuron and others, and this gap is called synapse.

There are mainly 3 type of neuron in our body

Not all neuron in our body have same structure and function. Neuron are classified into three main division, Unipolar, Bipolar, and Multipolar. (Fig. 1)

Unipolar : Their axon and dendrites are not separated by cell body, instead they fuse together. They also called Pseudouniplar neuron , because they actually develop from bipolar neuron.

Bipolar : This type neuron have one main dendrites and axon. Their main dendrites then branched form smaller dendrites. They are found mainly in retina eye, olfactory, and inner ear.

Multipolar : This neuron have several dendrites and one axon, they are majority found in brain and spinal cord.

Based on function, neuron are classified in three term, they are sensory neuron / afferent neuron, motor neuron / efferent neuron, interneuron / association neuron .

Sensory / Afferent Neuron : This neuron role in ‘catching” the stimulus from outside or from inside. Stimulus from outside for instance is pressure, heat, pain, etc. and stimulus from inside for instance blood pressure, hungry, exhausted, etc.  This neuron contain receptor, which being “the catcher” for stimulus. There so many receptor in our body. In common, receptor are categorized into five type, they are : mechanoreceptor, thermoreceptor , chemical receptor, nocireceptor,  electromagnetic receptor, and chemoreceptor.

a.       Mechanoreceptor respond into compression or streching of tissue adjacent to the receptor. Kind of this receptor is : muscle spindle, golgi tendon receptor, barroreceptor, merkel disc, meissner corpuscle, krause’ corpuscle, etc.

b.      Temperature receptor : respond into change of temperature. Kind of this receptor are cold receptor and warmth receptor

c.       Nocireceptor : respond into pain sensation. Detecting damaged area of the tissue. Kind of this receptor is free neve ending

d.      Electromagnetic receptor : respond to light sense, this receptor are located in retina. Kind of this receptor is cones and rod cells

e.      Chemoreceptor : respond to chemical change like taste, smell, chemical concentration molecule like oxygen level in the arterial blood vessel, carbon dioxide concentration, blood glucose and other factor that correlate with chemical mechanism. Kind of this receptor is receptor of taste buds, receptor of olfactory epithelium,  receptor in hypothalamus

(Guyton, 2007)

Stimulus that catch by receptor will bring to CNS by spinal nervous or cranial nervous. Most of sensory neuron is unipolar neuron ( Tortora, 2009)

Motor Neuron : This neuron have function to innervate muscle or gland in our body as a respond a command from brain or spinal cord to the effector. Most of motor neuron is multipolar.

Interneuron : This neuron act like bridge between sensory neuron and motor neuron. They are mainly located in CNS.

Neuron support by cells called Neuroglia.

Neuroglia in CNS consist oligodendrocyte, astrocyte, epindhymal , and microglia. Which each of them has different function. Oligodendrocyte function is to myelinated neuron in CNS, astrocyte mainly role in provide blood-brain barrier in CNS. Epindymal role in provide blood-cerebrospinal barrier  and also regulate CSF by produce, monitoring, and assist circulation. Microglia act “like-macropahge” for neuron.  they remove cellular debris formed during

normal development of the nervous system and phagocytize microbes and damaged nervous tissue.

Neuroglia in PNS (Peripheral-nervous-system) consist Scwan cell and Satelite cell. Scwan cell  act mainly in myelinated neuron and satelite cell act  mainly regulate exchange material between neuron cell body and interstitial fluid.

Nervous system is divided into CNS and PNS

Actually nervous system is divided into two different system, CNS and PNS. They are divided because they have different function and structure that involve in each system . CNS is central nervous system. This system include brain and spinal cord. And PNS is peripheral nervous system. This system was located in outside of CNS . Although they are separated, they are work together to mantain our body to work well.

·         CNS

CNS is a complex system. Actually, not only one way or one region that use by this system, but they need many way as an integrative process. This system is source of think, sleep, fright, hungry, emotion, and others. This system involve Brain ( Cortical and subcortical level) and spinal cord

·         PNS

PNS is a system that located in outside of CNS. This involve cranial nervous, spinal nervous, ganglia, and sensory receptor. Their majority function is like a “detector” and then send to CNS for processing. PNS was divided into 3 division. SNS (somatic nervous system), ANS (autonomic nervous system), and ENS ( enteric nervous system)

a.       SNS (somatic nervous system)

SNS is voluntary system, and the part where they operate is in skeletal muscle

b.      ANS (autonimic nervous system)

ANS is involumtary system, they consist of sympathetic and parasympathetic. They have opposite function (but not all of their function is opposited). For instance sympathetic nerve will regulate in increasing heart rate and parasympathetic nerve will decreasing. They work together for provide appropriate condition for us. Sympathetic support exercise or emergency action called “fight or flight” and parasympathetic role in “rest and digest” activity

c.       ENS (Enteric Nervous System)

ENS role in Gastro Intestinal (GI) mainly in the gut. Although some of their neuron also communicate with CNS via sympathetiv and parasympathetic but many of their neuron function independenly. Their role include contraction of GI tract smooth muscle to propel food through the GI tract, secretions of the GI tract organs such as acid from the stomach, and activity of GI tract endocrine cells, which secrete hormones.

How Neuron can communicate with each other ?

We know that neuron is not really bind with other, but they remain a gap called synapse. If there are a gap, how neuron transmit their information. Okey, before it, we should know what the information that used neuron to communicate first. Information that use neuron to communicate with other called impulse or action potential and graded potential. They are  different in function. Impulse mainly use to communicate in a long way., and gradedd potential mainly use to communicate in short way.  

A.   Nerve action potential

Action potential in nerve called nerve action potential. Like muscle cell, this action potential use term of depolarize and hyperpolarize, this mechanism basicly used ions to cause depolarize or hyperpolarize.

 Neuron are fully charge with ion (Cl^-, K⁺, Na⁺, PO₄^2- and Ca²⁺⁾ along their outer surface or in the inner surface. In resting condition (no impulse) Inner charge is more negative than outer charge because uneven concentration Phospate  ion (this phospate is come from ATP) and K ion. The range is about -40 mV until -90 mV. But commonly is -70 mV. This called resting membrane potential. Neuron contain ion channel where allow the specific ion to enter and out to make the change in membran potential.

Some type ion channel was found and has been identified their function

·         Na⁺ - K⁺ Leakage Channel

This channel is permeable both of Na⁺ or K⁺, but more permeable for K⁺ until 100 times than Na⁺

·         Ligand-gate Channel

This channel only can be opened by the presence of ligand in their binding site. The ligand including hormone, neurotransmitter, and particular ion. Example of this channel is cholinergic and andrenergic receptor for depolarization (allow Na⁺ or K⁺ ) and glycine receptor for hyperpolarization (Allow Cl^-).

·         Mechanical gate channel

Open and close by stimulation of mechanic stimulus such vibration or sound, touch, pressure, and tissue stretching. The force distorts the channel from its resting position, opening the gate. Examples of mechanically gated channels are those found in auditory receptors in the ears, in receptors that monitor stretching of internal organs, and in touch receptors and pressure

receptors in the skin.

·         Voltage gate channel

This channel respond in stimulus of voltage that change membrane potential. This channel are found in all of neuron.

To become impulse, a stimulus should reach a threshold potential, the amount is usually +40 mV. When the stimulus can reach this threshold, nerve action potential will apear, and it will distribute along the pathway with the same amount (potential) from which it firstly appear.

How the mechanism impulse rise from the stimulus?

As we talk before, when in resting condition, membrane potential of nerve is about -70 mV (depend on what type of the neuron), when the stimulus come, it cause the permeability membrane of Na⁺ incraese, and Na⁺ influx will also increase This happen because voltage-gate channel for Na⁺ open. The influx cause the inner membrane become depolarize until threshold potential and generate the impuls. After it, the voltage-gate K⁺ open, allow K⁺ to flow out and cause decrease in potential membrane into resting potential membrane (each neuron type has different resting potential membrane)., this called repolarize. If this voltage remain opened when resting potential membrane has been reached, it will make potential membrane more negative than resting potential, and this is called after-hyperpolarizing  . Action potential appear from  part of axon near axon hillock called triger zone. And then propagate along the neuron until axon terminal. Action potential propagation in myelinated neuron is more rapid than in unmyelinated neuron. It happen because myelinated neuron has node ranvier, which rich of ion channel. Conversely, there are poor ion channel in region where myelin sheath cover with axolemma. So there are uneven distribution of ion channel in myelinated axon. This will make action potential propagate like “jumping” from one node to other node, this is called “saltatory conduction”. In contrast, unmyelinated axon doesnt have node ranvier, and the distribution of ion channel in axon is equal every region, so the action potential propagate like “walk regularly” until reach axon terminal, this is called “continous conduction” (Fig 2).

Rate of transmission/propagation action potensial depend on :

1.       Amount of myelin sheath : as we talk before, propagation in myelinated neuron is more rapid than unmyelinated neuron, because the amount of ion channel that distributed

2.       Diameter of axon : Neuron which have large diameter of axon propagate more rapid than small diameter.

3.       Temperature : Temperatu1         `re also influence the rate of  propagation. In cold condition, impulse propagate more slowly, so this is the reason why in some injury, they firstly compressed with cold material (ice, chemical, etc)

There are a known as “refractory period” in action potential

An action potential in not a continous waves, instead need a perioad to propagate impulse again, when neuron generate first action potential, they need a time to generate second action potential.  This time is  called “refractory period”. Refractory period separate into two term. Absolute Refractory Period and Relative refractory period.

a.       Absolute Refractory Period

Absolute refractory period happen when an action potential cannot generate even with strong stimulus. This periode coincide with Na⁺ channel activation and inactivation. When Na⁺ channel inactivated, they will not activated again until the potential membrane bact to resting potential membrane first.

In large diameter of axon, they have brief refractory period, only about 0.4 msec. so they can generate impulse up to 1000 impulse per second. In smal-diameter axon, they have refractory period 10 time longer than large-diameter, about 4 msec. and enabling them to transmit 250 impulse per second.

b.      Relative Refractory Period

Relative refractory period happen when an action potentital cannot generate impuls by normal stimulus but they can generate it with strong stimulus. It coincides with the period when the

voltage-gated K⁺ channels are still open after inactivated Na⁺ channels have returned to their resting state.

The Amplitude of impuse always same in every condition

The Amplitude or “the size” of Impuse/action potential is not depend on how big the stimulus that stimulate him. As long as the stimulus can reach threshold, it can generate impulse, it have a current amplitude. Although there are big stimulus “suprathreshold stimulus” stimulate the neuron, it will have the same amplitude like normal stimulus. This work mechanism called “all or none”. Action potential depend on can or cannot a stimulus reach threshold, if they can, they will generate impus, if not, they cannot generate impulse.

Action potential cannot diminimish until they reach the site of their purpose

Graded Potential

Like what i talk before, graded potential is different from action potential. Graded potential mainly use to communicate in short distance between neuron. They dont generate impulse, because the stimulus never reach threshold level. They can be more polarize to more negative or less polarize to less negative. Their special characteristic is generate vary amplitude when tested using oscilloscope, and they depend in the strength of stimulus. Really contrast with action potential Graded potential mainly occur in the dendrite and cell body of neuron.

This is use ligand-gate or mechanically gated as the entrance of ion, and leakeage for the escape. Because this mechanism, graded potential can lost or die called decremental. Graded potential is not experiencing refractory period. If there are two continous stimulus, they will combine. And the result is like “calculation process” . if they are two stimulus or more that have the same desire to depolarizing  the membrane, the amplitute will add together into larger potential (more positive). If they are two stimulus or more that have the same desire to hyperpolarizing the membrane, the amplitude will add together into smaller potential (more negative). And if they are two stimulus or more that have opposite mechanism, the result potential is summation all of it like summation between positive and negative number.

Transmission between one neuron to other cells ( neuron, muscle, or gland)

We believe that there are a gap between neuron called synapse. Synapse is using for communication in neuron cells, both of neuron-neuron or neuron-other cells, there always present a synapse. In synapse, the part that send signal is called presynaptic . And part that accept the signal is called postsynaptic. At communication between neuron to neuron, its called presynaptic neuron and post synaptic neuron. In neuron synapse can happen between axon and dendrite (axodendritic), axon-cell body (axosomatic), and axon-axon (axoaxonic).

Type communication in synapse divided into two, electrical synapse and chemical synapse.

a.       Electrical Synapse

Action potential conduct directly in synapse through structure act like tunnel called conexon This connexon was located in structure called gap junction. Gap junction mainly located in visceral smooth muscle, cardiac muscle, and the developing embryo. They also occur in the CNS.

The adventages of this typical synapse are :

1.       They transmit impuls faster than in chemical synapse

2.       It can make synchronization. Example of this is in heart beat

b.      Chemical synapse

To transmit signal in this type, a neuron using neurotransmitter that save in a “pocket” called vesicle. This vesicle is located in presynaptic neuron. Presynaptic neuron and postsynaptic neuron was separated for about 20-50 nm, this space called “synaptic cleft”. Chemical synapse transmit slower than electrical synapse because there are “delayed-time” for about 0.5 msec. called synaptic delay. This time actually to obtain neurotransmitter (elaborate later) and generate other vesicle to release their neurotransmitter in axon terminal. Impulse transmission in chemical synapse occur only in one-way-dirrection, this is because neurotransmitter only located in presynaptic neuron

Neurotransmitter as a mediator to transmit impuls to one neuron to another neuron

After we know about impuls, arise a question, how impuls can transmit to another neuron whereas neuron is not really connected, instead make a gap called synapse? The answer is neuron using neurotransmitter. What is neurotransmitter? neurotransmitter is chemical substance that act with binding its receptor and open the specific channel to conduct their function. Many neurotransmitters have been identified. Major neurotransmitter in our body is cholinergic, adrenergic, GABA, glycine, serotonine, and histamine. But actually there are more than 50, which categorize into several subclass.

This is the categorization based on Guyton :

Class I	·         Acetylcholine
Class II: The Amines	·         Norepinephrine ·         Epinephrine ·         Dopamine ·         Serotonin ·         Histamine
Class III: Amino Acids	·         Gamma-aminobutyric acid (GABA) ·         Glycine ·         Glutamate ·         Aspartate
Class IV	·         Nitric oxide (NO)
Hypothalamic-releasing hormones	·         Thyrotropin-releasing hormone ·         Luteinizing hormone–releasing hormone ·         Somatostatin (growth hormone inhibitory factor)
Pituitary peptides	·         Adrenocorticotropic hormone (ACTH) ·         b-Endorphin ·         a-Melanocyte-stimulating hormone ·         Prolactin ·         Luteinizing hormone ·         Thyrotropin ·         Growth hormone ·         Vasopressin ·         Oxytocin
Peptides that act on gut and brain	·         Leucine enkephalin ·         Methionine enkephalin ·         Substance P ·         Gastrin ·         Cholecystokinin ·         Vasoactive intestinal polypeptide (VIP) ·         Nerve growth factor ·         Brain-derived neurotropic factor ·         Neurotensin ·         Insulin ·         Glucagon
From other tissues	·         Angiotensin II ·         Bradykinin ·         Carnosine ·         Sleep peptides ·         Calcitonin

Neurotransmitter is saved in vesicle through “ion pumping” mechanism

Major neurotransmitter are synthesized  in cytoplasm or outside of neuron but not in the vesicle. ATP-dependent transporter pump proton from the cytoplasm to the vesicle, thereby creating a proton gradient across the vesicle membrane. The electrochemical energy in this proton gradient is used to provide specialized neurotransmitter transporters with the fuel for active transport of neurotransmitter molecules from the cytoplasm into the vesicle.

Neurotransmitter Receptor

Neurotransmitter receptor has categorize into two based on wheter its neurotransmitter bindng site. They are Ionotopic Receptor and Metabotropic Receptor

a.       Ionotropic Receptor

Ionotropic receptor is type of receptor, which the ion channels and neurotransmitter binding site are located on the same protein (receptor is a kind of protein). This receptor represent of ligand-gated receptor. Example of this receptor is Acetylcholine receptor, β-receptor, α-receptor.

b.      Metabotropic Receptor

A metabotropic receptor is a type of neurotransmitter receptor that contains a neurotransmitter binding site, but lacks an ion channel as part of its structure.  Thus, it uses other ion channel to function well. To communicate with this ion channel, a metabolic receptor cooperate with G-protein, who it will activate second messenger to open the ion channel. Example of this receptor is metabotropic acethylcholine receptor, when it is opened, it will allow K+ to outward, and cause inhibitory postsynaptic potentital. (acetylcholine act different in different receptor)

How the process of neurotransmitter conduct transmission of information ?

·         First, when action potential occur, they lead for opening of Ca²⁺ Channel, thus Ca2+ enter to the neuron. Increasing Ca2+ influx will facilitate proteins that mediated bindinf of vesicle into axon terminal plasma membrane. This proteins are synapsin and SNARE ((soluble N-ethylmaleimide-sensitive factor [NSF]-attachment protein receptor)

·         Binding of vesicle into plasm membrane cause exocytosis, and vesicle release neurotransmitter into synaptic cleft.

·         Then, neurotransmitters bind to their receptor (ionotropic or metabotropic), and lead to opening channel to allow specific ion to enter and cause alteration in the postsynaptic potential, it can be excitatory or inhibitory, dependent on what type of neurotransmitter and what type of ions that enter the postsynaptic membrane.

·         This process occur very – very brief, usually, neurotransmitter then remove by removal enzyme (the most famous enzyme is acetylcholine esterase) or reuptake again by endocytosis process and then save in vesicle again for next transmission

Actually single postsynaptic neuron can receive from many presynaptic neuron (Fig. 3), and this presynaptic can same type of neuron, and also different type of neuron. This is called summation (as we learn in graded potential). There are two summation, spatial summation and temporal summation. Spatial summation is summation of postsynaptic potentials in response to stimuli that occur at different locations in the membrane of a postsynaptic cell at the same time. For example, spatial summation results from the buildup of neurotransmitter released simultaneously by several presynaptic end bulbs.  Temporal summation is summation of postsynaptic potentials in response to stimuli that occur at the same location in the membrane of the postsynaptic cell but at different times. For example, temporal summation results from buildup of neurotransmitter released by a single presynaptic end bulb two or more times in rapid succession. Thus, there are several occurance that maybe happen in communication of neurons in synaptic cleft.

1. EPSP. If the total excitatory effects are greater than the total inhibitory effects but less than the threshold level of stimulation, the result is an EPSP that does not reach threshold. Following an EPSP, subsequent stimuli can more easily generate a nerve impulse through summation because the neuron is partially depolarized.

2. Nerve impulse(s). If the total excitatory effects are greater than the total inhibitory effects and threshold is reached, one or more nerve impulses (action potentials) will be triggered. Impulses continue to be generated as long as the EPSP is at or above the threshold level.

3. IPSP. If the total inhibitory effects are greater than the excitatory effects, the membrane hyperpolarizes (IPSP). The result is inhibition of the postsynaptic neuron and an inability to generate a nerve impulse.

SUMMARY

I don’t want to summarize this from the beginning to the end, because , this is actually a summary from text book plus my cogitation, hehe. Its my story, where is your story? (Ini ceritaku, mana ceritamu)……………………….. to be continue

Mainly Source :

Guyton AC, Hall JE. 2007. Textbook of medical physiology. 11^th ed. Elsevier

Tortura GJ, Derricson B. 2009. Principle of anatomy and physiology. 9^th ed. John Wiley and Son.

Sejati, NES. 2013. Cogitation and Integrative Thinking. First edition. Terbit Sendiri ( ^.^) *peace*

Figure 1. Neurons are categorize into multipolar, bipolar, and unipolar

 Figure 2. Transmission of neuron in myelinated neuron and unmyelinated neuron

Figure 3. postsynaptic neuron receive more than one of presynaptic neuron