TERM PAPER OF ANIMAL BIOTECH.

(BTY305) TOPIC: NEURON CELL & ITS APPLICATION

SUBMITTED TO

SUBMITTED TO: PRITI SINGH REG.NO. :- 3440070133 B.TECH BIOTECH (MBA) ROLL NO. B7703A13

ACKNOWLEDGEMENT

I, priti hereby take the advantage to thank my teacher Mr for assigning me such a wonderful topic for my term paper& extending me consistent help, support & guiding throughout the project.

Also, I will like to thank my friends for aiding me with the requisite materials & information for my project. My immeasurable gratitude to my roommates & my parents cannot be expressed in words for the support they have provided.

PRITI SINGH

INTROCUCTION
NEURONS

A typical neuron has all the parts that any cell would have, and a few specialized structures that set it apart. The main portion of the cell is called the soma or cell body. It contains the nucleus, which in turn contains the genetic material in the form of chromosomes.

Neurons have a large number of extensions called dendrites. They often look likes branches or spikes extending out from the cell body. It is primarily the surfaces of the dendrites that receive chemical messages from other neurons.

One extension is different from all the others, and is called the axon. Although in some neurons, it is hard to distinguish from the dendrites, in others it is easily distinguished by its length. The purpose of the axon is to transmit an electro-chemical signal to other neurons, sometimes over a considerable distance. In the neurons that make up the nerves running from the spinal cord to your toes, the axons can be as long as three feet!

Longer axons are usually covered with a myelin sheath, a series of fatty cells which have wrapped around an axon many times. These make the axon look like a necklace of sausage-

shaped beads. They serve a similar function as the insulation around electrical wire.

At the very end of the axon is the axon ending, which goes by a variety of names such as the bouton, the synaptic knob, the axon foot, and so on (I do not know why no one has settled on a consistent term!). It is there that the electro-chemical signal that has travelled the length of the axon is converted into a chemical message that travels to the next neuron.

Between the axon ending and the dendrite of the next neuron is a very tiny gap called the synapse (or synaptic gap, or synaptic cleft), which we will discuss in a little bit. For every neuron, there are between 1000 and 10,000 synapses.

HISTOLOGY AND INTERNAL STRUCTURE

GOLGI-STAINED NEURONS IN HUMAN HIPPOCAMPAL TISSUE. Nerve cell bodies stained with basophilic dyes show numerous microscopic clumps of Nissl substance (named after German psychiatrist and neuropathology Franz Nissl, 18601919), which consists of rough endoplasmic reticulum and associated ribosomal RNA. The prominence of the Nissl substance can be explained by the fact that nerve cells are metabolically very active, and hence are involved in large amounts of protein synthesis. The cell body of a neuron is supported by a complex meshwork of structural proteins called neurofilaments, which are assembled into larger neurofibrils. Some neurons also contain pigment granules, such as neuromelanin (a brownish-black pigment, byproduct of synthesis of catecholamines) and lipofuscin (yellowish-brown pigment that accumulates with age).

PARTS OF THE NERVE CELL AND THEIR FUNCTIONS

Neurons are specialized cells. They are made to receive certains specific connections, to perform appropriate functions and pass their decision of a particular event to other neurons which are also concerned with those events. These specializations include a cell membrane, which is specialized to convey nerve signals as electrochemical pulses; the dendrite, which gets and delivers the signals, the axon, the conducting cable of electrical signals, and points of synaptic contacts, where information can be passed on from one cell to another

1 CELL BODY

The cell body (soma) is the factory of the neuron. It produces all the proteins for the dendrites, axons and synaptic terminals and contains specialized organelles such as the mitochondria, Golgi apparatus, endoplasmic reticulum, secretary granules, ribosome and polysomes to provide energy and make the parts, as well as a production line to assemble the parts into completed products. CYTOSOL - Is the watery and salty fluid with a potassium-rich solution inside the cell containing enzymes responsible for the metabolism of the cell. 1. Nucleus - Derived from the Latin word for "nux", nut, the nucleus is the archivist and the architect of the cell. As archivist it contains the genes, consisting of DNA which contains the cell history, the basic information to manufacture all the proteins characteristic of that cell. As architect, it synthesizes RNA from DNA and ships it through its pores to the cytoplasm for use in protein synthesis. The. Nucleolus is an organelle within the nucleus which is involved actively in ribosome synthesis and in the transfer of RNA to the cytosol.

2. Golgi Apparatus - membrane-bound structure that plays a role in packaging peptides and proteins (including neurotransmitters) into vesicles. 3. Polyribosome - there are several free ribosome attached by a thread. The thread is a single strand of mRNA (messenger RNA, a molecule involved in the synthesis of proteins outside the nucleus). The associated ribosome work on it to make multiple copies of the same protein. 4. Neuronal membrane 5. Mitochondria - this is the part of the cell responsible for the supply of energy in the form of ATP (adenosine triphosphate). Neurons need an enormous amount of energy. The brain is one of the most metabolically active tissues in the body.. 6. Rough Endoplasmic Reticulum and Smooth Endoplasmic Reticulum (7) - A system of tubes for the transportation of materials within the cytoplasm. It may have ribosomes (rough ER) or no ribosomes (smooth ER). With ribosomes, the ER is important for protein synthesis. Nissl Bodies - Groups of ribosomes used for protein synthesis.

NEURONALMEMBRANE

2.

The neuronal membrane serves as a barrier to enclose the cytoplasm inside the neuron, and to exclude certain substances that float in the fluid that bathes the neuron. The membrane with its mosaic of proteins is responsible for many important functions: The membrane is made of lipids and proteins - fats and chains of aminoacids. The basic structure of this membrane is a bilayer or sandwich of phospholipids, organized in such a way that the polar (charged) regions face outward and the non polar regions face inward. The external face of the membrane contains the receptors, small specialized molecular regions which provide a kind of "attachment port" for other external molecules, in a scheme analogous to a a key and a keyhole. 3.

DENDRITES

These structures branch out in treelike fashion and serve as the main apparatus for receiving signals from other nerve cells. They function as an "antennae" of the neuron and are covered by thousands of synapses. The dendritic membrane under the synapse (the post-synaptic membrane) has many specialized protein molecules called receptors that detect the neurotransmitters in the synaptic cleft..

4-

AXON

Usually a long process which often projects to distant regions of the nervous system. The axon is the main conducting unit of the neuron, capable of conveying electrical signals along distances that range from as short as 0.1 mm to as long as 2 m. Many axon split into several branches, thereby conveying information to different targets. Many neurons do not have axons. In these so-called amacrine neurons, all the neuronal processess are dendrites. Neurons with very short axons are also found. The cells that wrap around peripheral nerve fibers - that is, nerve fibers outside of the brain and spinal cord - are called Schwann cells (because they were first described by Theodor Schwann). The cells that wrap around axons within the central nervous system (brain and spinal cord) are called oligodendrocytes. The axon, with its surrounded sheath, is called a nerve fiber. Between each pair of sucessive Schwann cells is a gap of a node of Ranvier. The Axon Hillock The axon hillock is where the axon is joined to the cell. It is from here that the electrical firing known as an action potential usually occurs.

5. NERVE ENDING (PRESYNAPTIC TERMINALS)

Synapses are the junctions formed with other nerve cells where the presynaptic terminal of one cell comes into 'contact' with the postsynaptic membrane of another. It is at these junctions that neurons are excited, inhibited, or modulated. There are two types of synapse, electrical and chemical. Electrical synapses occur where the presynaptic terminal is in electrical continuity with the

postsynaptic. Ions and small molecules passing through, thus connecting channels from one cell to the next, so that electrical changes in one cell are transmitted almost instantaneously to the next. Ions can generally flow both ways at these junctions i.e. they tend to be bidirectional, although there are electrical junctions where the ions can only flow one way, these are know as rectifying junctions. Rectifying junctions are used to synchronise the firing of nerve cells. Chemical synaptic junction is more complicated. The gap between the post- and presynaptic terminals is larger, and the mode of transmission is not electrical, but carried by neurotransmitters, neuroactive substances released at the presynaptic side of the junction. There are two types of chemical junctions. Type I is an excitatory synapse, generally found on dendrites, type II is an inhibitory synapse, generally found on cell bodies. Different substances are released at these two types of synapse. The direction of flow of information is usually one way at these junctions. Each terminal button is connected to other neurons across a small gap called a synapse. The physical and neurochemical characteristics of each synapse determines the strength and polarity of the new input signal. This is where the brain is the most flexible, and the most vulnerable. Changing the constitution of various neurotransmitter chemicals can increase or decrease the amount of stimulation that the firing axon imparts on the neighbouring dendrite. Altering the neurotransmitters can also change whether the stimulation is excitatory or inhibitory.

TYPES OF NEURONS
While there are many different kinds of neurons, there are three broad categories based on function:

1. SENSORY NEURONS are sensitive to various non-neural stimuli. There are sensory neurons in the skin, muscles, joints, and organs that indicate pressure, temperature, and pain. There are more specialized neurons in the nose and tongue that are sensitive to the molecular

shapes we perceive as tastes and smells. 2. MOTOR NEURONS are able to stimulate muscle cells throughout the body, including the muscles of the heart, diaphragm, intestines, bladder, and glands.

3. INTERNEURONS are the neurons that provide connections between sensory and motor neurons, as well as between themselves. The neurons of the central nervous system, including the brain, are all interneurons.

Most neurons are collected into "packages" of one sort or another, sometimes visible to the naked eye. A clump of neuron cell bodies, for example, is called a ganglion (plural: ganglia) or a nucleus (plural: nuclei). A fiber made up of many axons is called a nerve. In the brain and spinal cord, areas that are mostly axons are called white matter, and it is possible to differentiate pathways or tracts of these axons. Areas that include large number of cell bodies are called gray matter.

FUNCTION

THE ACTION POTENTIAL

when chemicals contact the surface of a neuron, they change the balance of ions (electrically charged atoms) between the inside and outside of the cell membrane. When this change reaches a threshold level, this effect runs across the cell's membrane to the axon. When it reaches the axon, it initiates the action potential, which is a rapidly moving exchange of ions.

The surface of the axon contains hundreds of thousands of miniscule mechanisms called ion channels. When the charge enters the axon, the ion channels at the base of the axon allow positively charged ions to enter the axon, changing the electrical balance between inside and

outside. This causes the next group of ion channels to do the same, while other channels return positive ions to the outside, and so on all the way down the axon.

THE SYNAPSE

When the action potential reaches the axon ending, it causes tiny bubbles of chemicals called vesicles to release their contents into the synaptic gap. These chemicals are called neurotransmitters. These sail across the gap to the next neuron, where they find special places on the cell membrane of the next neuron called receptor sites.

The neurotransmitter acts like a little key, and the receptor site like a little lock. When they meet, they open a passage way for ions, which then change the balance of ions on the outside and the inside of the next neuron. And the whole process starts all over again.

While most neurotransmitters are excitatory -- i.e. they excite the next neuron -- there are also inhibitory neurotransmitters. These make it more difficult for the excitatory neurotransmitters to

have their effect.

RECOGNITION NEURONS One form of learning that we all use every minute of every day may be the best chance of substantiating a direct link between a form of learning and an experimentally derived form of synaptic plasticity - visual recognition memory and LTD. The visual recognition memory system that resides in a region of the brain known as the perirhinal cortex . Certain neurons in this area respond in such a way as to discriminate between objects that have not been seen before (novelty neurons), those that have been seen before (familiarity neurons) and those that have been seen recently (recency neurons). In each case, the response of the neuron is decreased following stimulation. Thus, a novelty neuron responds strongly when presented with a novel object, but less strongly when that object is presented SPONTANEOUS OBJECT RECOGNITION

There are many different tasks that can be used to investigate recognition memory. One of the simplest is the spontaneous object recognition task. In this task, a rat or mouse is placed in an arena with two identical objects and allowed to explore them. After a while, the animal is removed for a pre-determined period of time and then returned to the arena where an identical copy of the original object (familiar object) is still in place along with a new object that the animal has not seen before (novel object). The rat or mouse will then tend to explore the novel object more than the familiar one. And its not just rodents that do this - we do it as well! Loss of function in the perirhinal cortex results in a loss in the ability to perform this task .... ie the animal loses the ability to recognise that they've seen the object before COMMUNICATION

Neurons communicate at structures called synapses in a process called synaptic transmission. The synapse consists of the two neurons, one of which is sending information to the other. The sending neuron is known as the pre-synaptic neuron (i.e. before the synapse) while the receiving neuron is known as the post-synaptic neuron (i.e. after the synapse). Although the flow of information around the brain is achieved by electrical activity, communication between neurons is a chemical process. When an action potential reaches a synapse, pores in the cell membrane are opened allowing an influx of calcium ions (positively charged calcium atoms) into the presynaptic terminal. This causes a small 'packet' of a chemical neurotransmitter to be released into a small gap between the two cells, known as the synaptic cleft. The neurotransmitter diffuses across the synaptic cleft and interacts with specialized proteins called receptors that are embedded in the post-synaptic membrane. These receptors are ion channels that allow certain types of ions (charged atoms) to pass through a pore within their structure. The pore is opened following interaction with the neurotransmitter allowing an influx of ions into the post-synaptic terminal, which is propagated along the dendrite towards the soma

APPLICATION

y NEURON CELL STICKINESS MAY HOLD KEY TO EVOLUTION OF THE HUMAN BRAIN
In a paper published in the Nov 3, 2006 issue of the journal Science, a team of researchers led by Edward Rubin, MD, director of both JGI and Berkeley Labs Genomics Division, report on a comparative genomics study of conserved noncoding sequences (CNSs) - sequences of DNA shared by many different organisms that do not code for proteins but play an important role in regulating gene expression. In their Science paper, the researchers identified 992 CNSs whose sequences were specifically modified in humans and enriched near genes involved in neuronal cell adhesion. This is the first genome-wide unbiased study to detect clear evidence of humanspecific evolution in brain-related sequences. After further comparisons, the researchers concluded these CNSs may have contributed to the uniquely human features of brain development and function.

y COMPUTATIONAL PREDICTION OF NEURAL PROGENITOR CELL FATES

Understanding how stem and progenitor cells choose between alternative cell fates is a major challenge in developmental biology. Efforts to tackle this problem have been hampered by the scarcity of markers that can be used to predict cell division outcomes. Here we present a computational method, based on algorithmic information theory, to analyze dynamic features of living cells over time. Using this method, we asked whether rat retinal progenitor cells (RPCs) display characteristic phenotypes before undergoing mitosis that could foretell their fate. We

predicted whether RPCs will undergo a self-renewing or terminal division with 99% accuracy, or whether they will produce two photoreceptors or another combination of offspring with 87% accuracy. Our implementation can segment, track and generate predictions for 40 cells simultaneously on a standard computer at 5 min per frame. This method could be used to isolate cell populations with specific developmental potential, enabling previously impossible investigations.

y STEM CELL INFORMATION

Researchers use the signaling molecules that selectively adhere to the receptors on the surface of the cell as a tool that allows them to identify stem cells. Many years ago, a technique was developed to attach to the signaling molecule another molecule (or the tag) that has the ability to fluoresce or emit light energy when activated by an energy source such as an ultraviolet light or laser beam (see Figure E.i.1. Identifying Cell Surface Markers Using Fluorescent Tags). At the researchers' disposal are multiple fluorescent tags with emitted light that differ in color and intensity.

Figure

E.i.1.

Identifying

Cell

Surface

Markers

Using

Fluorescent

Tags.

Described here are two approaches of how researchers use the combination of the chemical

properties of fluorescence and unique receptor patterns on cell surfaces to identify specific populations of stem cells.

Figure E.i.2. Looking for a Needle in a Haystack: How Researchers Find Stem Cells. A second method uses stem cell markers and their fluorescent tags to visually assess cells as they exist in tissues. Often researchers want to assess how stem cells appear in tissues and in doing so they use a microscope to evaluate them rather than the FACS instrument. In this case, a thin slice of tissue is prepared, and the stem cell markers are tagged by the signaling molecule that has the fluorescent tag attached. The fluorescent tags are then activated either by special light energy or a chemical reaction. The stem cells will emit a fluorescent light that can easily be seen under the microscope.

Genetic and molecular biology techniques are extensively used to study how cells become specialized in the organism's development. In doing so, researchers have identified genes and transcription factors (proteins found within cells that regulate a gene's activity) that are unique in stem cells. Scientists use techniques such as polymerase chain reaction (PCR) to detect the presence of genes that are "active" and play a role guiding the specialization of a cell. This technique has is helpful to researchers to identify "genetic markers" that are characteristic of stem cells. For example, a gene marker called PDX-1 is specific for a transcription factor protein that initiates activation of the insulin gene. Researchers use this marker to identify cells that are able to develop islet cells in the pancreas. Recently, researchers have applied a genetic engineering approach that uses fluorescence, but isn't dependent on cell surface markers. The importance of this new technique is that it allows the tracking of stem cells as they differentiate or become specialized. Scientists have inserted into a stem cell a "reporter gene" called green fluorescent protein or GFP [2]. The gene is only activated or "reports" when cells are undifferentiated and is turned off once they become specialized. Once activated, the gene directs the stem cells to produce a protein that fluoresces in a brilliant green color (see Figure E.i.3. Microscopic Image of Fluorescent-Labeled Stem Cell). Researchers are now coupling this reporting method with the FACS and microscopic methods described earlier to sort cells, identify them in tissues, and now, track them as they differentiate or become specialized.

Figure

E.i.3.

Microscopic

Image

of

Fluorescent-Labeled

Stem

Cell.

These discovery tools are commonly used in research laboratories and clinics today, and will likely play important roles in advancing stem cell research. There are limitations, however. One of them is that a single marker identifying pluripotent stem cells, those stem cells that can make

any other cell, has yet to be found. As new types of stem cells are identified and research applications of them become increasingly complex, more sophisticated tools will be developed to meet investigators' needs. For the foreseeable future, markers will continue to play a major role in the rapidly evolving world of stem cell biology

y POLYGLUTAMINE DISEASE AND NEURONAL CELL DEATH

Research in the past decade has uncovered a new class of inherited neurodegenerative diseases, the polyglutamine (polyQ) expansion diseases (1). In each, the underlying mutation is an expansion of a CAG trinucleotide repeat that encodes polyQ in the respective disease proteins (Table 1). All are progressive, ultimately fatal disorders that typically begin in adulthood and progress over 10 to 30 years. The clinical features and pattern of neuronal degeneration differ among the diseases, yet increasing evidence suggests that polyQ diseases share important pathogenic features. In particular, abnormal protein conformation(s) promoted by polyQ expansion seem to be central to pathogenesis (2). PolyQ diseases thus join a growing group of neurodegenerative disorders, including Alzheimer's disease and many other dementias, in which abnormal protein folding and aggregation are implicated.

Neural stem cells and neurospheresre-evaluating the relationship

For most of the past century, the prospect of replacing lost or damaged cells in the central nervous system (CNS) was hampered by the opinion that the adult mammalian CNS was incapable of generating new nerve cells. This belief, like most dogmas, was essentially founded on a lack of experimental evidence to the contrary. The overturning of this 'no new neuron' hypothesis began midway through the twentieth century with a series of reports documenting neurogenesis in the postnatal and adult brain1, continued with the isolation and in vitro culture of neurogenic cells from the adult mammalian brain, and culminated in the discovery of a population of multipotent, self-renewing cells in the adult CNS (that is, bona fide neural stem cells) Although a variety of techniques were initially used, the neurosphere assay (NSA) rapidly

emerged as the assay of choice and has since become a valuable tool for isolating, and understanding the biology of, embryonic and adult CNS stem cells. Like all technologies, it is not without its limitations. In this article we will highlight several shortcomings of the assay related to its application and interpretation that we believe have led to a significant body of research whose conclusions may well be misleading.

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WWW.OVERVIEW OF NEURON STRUCTURE AND FUNCTION -- MOLECULAR CELL BIOLOGY -- NCBI BOOKSHELF.MHT y y y y WWW.NURON\COMMUNICATION.MHT WWW.NURON\MAJOR COMPONENTS OF A TYPICAL NEURON.MHT WWW.NURON\PARTS OF THE NERVE CELL AND THEIR FUNCTION.MHT WWW.NURON\NEURON CELL STICKINESS MAY HOLD KEY TO EVOLUTION OF THE HUMAN BRAIN.MHT y y WWW.\NURON\PLASTICITY.MHT HTTP://WWW.GLOBALCELLSOLUTIONS.COM/AUTOMATED3DCULTUREOFN EURALSTEMCELLS.PDF