STRUCTURE OF NEURONs Dr.NIKHIL.G.PANPALIA Guide: Dr.K.R.NAIK
Historical background
HISTORY OF NEURONS Cell theory In 1838 Theodore Schwann and Matthias Schleiden proposed that the cell was the basic functional unit of all living things. The complexity and small size of most neurons made elucidating the structure of the neuron the most formidable task in the field of histology, and the debate about the fine structure of the nervous system spanned most of the nineteenth century.
Purkinje’s work One of the first people to use the new compound microscopes to investigate nervous tissue was Johannes Evangelista Purkinje D opaminergic midbrain neurons Cerebellar cells which bear his name. Purkinje’s speculations on the functions of the entities he had discovered suggest that he contributed more to the Neuron Doctrine : “With reference to the importance of the corpuscles…they are probably central structures…because of their whole organization in three concentric circles [i.e. cytoplasm, nuclear membrane and nucleolus] which may be related to the elementary brain and nerve fibres …as centres of force are related to the conduction pathways of force, or like the ganglia to the nerves of the ganglion, or like the brain substance to the spinal cord and cranial nerves. This means they would be collectors, generators and distributors of the neural organ.” Johannes Evangelista Purkinje
Golgi contribution Staining method – Camillo Golgi (1843-1926, right). Golgi staining or Golgi impregnation - involves hardening of tissue in potassium bichromate and ammonia immersion in a silver nitrate solution. In 1873, Golgi published descriptions of hippocampal and cerebellar tissue that he had stained using his new technique. Golgi reasserts his belief that the nervous system consists of a reticulum . Camillo Golgi Hippocampus Cerebellum
Cajal work Santiago Ramón y Cajal (1852-1934) - neuron was the anatomical and functional of the nervous system. Cajal examined nervous tissue from embryos, - the axon and dendrites grow out of the cell body of the neuron. Cajal describes the basket cells in the molecular layer of the cerebellar cortex: “They are small, globular, and irregular…[and] supplied with numerous protoplasmic prolongations [dendrites]. The special character of these cells is the striking arrangement of their nerve filament [axon], which arises from the cell body but also very often from any thick, protoplasmic expansion [dendrite].” Chicken cerebellum by Santiago Ramony y Cajal
Neuron doctrine The neuron is the fundamental structural and functional unit of the nervous system Neurons are discrete cells which are not continuous with other cells The neuron is composed of 3 parts – the dendrites, axon and cell body, and Information flows along the neuron in one direction (Dendrites to the Axon, via the Cell body).
Neuron Term introduced in 1891. The axis cylinder Axon was coined by RudolphVon Kollicker protoplasmic processes Dendrites was termed by WilhelmHis Charles Sherrington described the junction between nerve and muscle, and named it the Synapse
Introduction
What is neuron ? Excitable cells specialized for reception of stimuli and conduction of impulses. Brain, Spinal cord and Ganglia No division and replication The human nervous system is estimated to consist of roughly 360 billion non-neural glial cells and 90 billion nerve cells. Neurons are post mitotic structures therefore they donot divide.
Neurons vs. Other Cells Similarities with other cells: Neurons and other body cells both contain a nucleus that holds genetic information. Neurons and other body cells are surrounded by a membrane that protects the cell. The cell bodies of both cell types contain organelles that support the life of the cell, including mitochondria, Golgi bodies, and cytoplasm. Differences that make neurons unique: Unlike other body cells, neurons stop reproducing shortly after birth. Neurons have a membrane that is designed to sends information to other cells. The axon and dendrites are specialized structures designed to transmit and receive information. The connections between cells are known as a synapses. Neurons release chemicals known as neurotransmitters into these synapses to communicate with other neurons.
Neurons consist of a main part called the cell body , which contains the nucleus and various organelles. Cell Body Nucleus Nucleolus
Neurons also contain cell body “extensions” called processes or neurites , which carry impulses to and from the cell body. axon Dendrites Two different types of processes can come from the cell body. The first is called the dendrite and the other the axon .
Dendrites , also called afferent processes , carry impulses TOWARDS the cell body. Axons , also called efferent processes , carry impulses AWAY from the cell body.
Types of neurons
Types of neurons Classified according three methods 1) Morphology 2) Size 3) Function
Unipolar neurons Unipolar neurons - cell body has a single neurite that divides a short distance from the cell body into two branches, one proceeding to some peripheral structure and the other entering the central nervous system . Examples -found in the posterior root ganglion. Unipolar neurons Cell body Dendrites
Multipolar neurons Multipolar neurons have a number of neurites arising from the cell body . With the exception of the long process, the axon, the remainder of the neurites are dendrites. Most neurons of the brain and spinal cord are of this type.
Bipolar neurons Bipolar neurons possess an elongated cell body, from each end of which a single neurite emerges . Examples of this type of neuron are found in the retinal bipolar cells and the cells of the sensory cochlear and vestibular ganglia.
According to size Golgi type I neurons have a long axon. Pyramidal cells of the cerebral cortex Purkinje cells of the cerebellar cortex Motor cells of the spinal cord Golgi type II neurons have a short axon cerebral and cerebellar cortex Pyramidal cells (Golgi Type I neurons Golgi Type ii Neuron Golgi Type ii Neuron
Functional classification Sensory or afferent neuron Motor or efferent neuron Interneuron or association neuron
Sensory neurons or Afferent neurons Periphery of the body to the Central nervous system. These neurons are usually concentrated in areas called ganglia and their dendrite branches extend to the skin or to sensory organs and act as sensory receptors (either directly or indirectly).
Motor neurons or Efferent neurons These neurons carry impulses Away from the cell body and thus the central nervous system to muscles, gland, or some other “ effector ” to produce a certain action. Most of the neurons in the spinal cord and many of those in the brain are motor neurons.
Interneurons or Association neurons This type of neuron is restricted to the central nervous system. They are also called connector neurons. These neurons act as bridges between sensory and motor neurons or relay impulses to various functional centers of the brain or spinal cord.
Structure of neuron
Structure of neurons Cell body and its organelles Plasma membrane Nerve cells processes
Main structures of Cell body Nucleus Cytoplasmic organelles
Nucleus of cell body Large, rounded Appears Pale, chromatin widely scattered; single prominent nucleolus; Barr body present in female Located centrally placed, displaced to periphery in cell injury Functions in controlling cell activity Meshwork of neuronal and glial processes are collectively termed as neuropil Dendrites Nucleus Nucleolus Body of nerve cell neuropil Photomicrograph - Section Anterior grey column of Spinal cord
Nucleolus Structure - Small circular structure(s) within nucleus Function(s) -Synthesis and partial assembly of ribosomes
Cytoplasm and its organalles Cytoplasm is rich in granular and agranular substance. Suspends the organelles within the cell Fills the cell and gives it shape Allows nutrients to move about the cell Following are the cytoplasmic organalles
Nissls substance Nissl substance consists of granules that are distributed throughout the cytoplasm of the cell body, except for the region close to the axon, called the axon hillock . The granular material also extends into the proximal parts of the dendrites; it is not present in the axon. Appearance : Nissl substance is composed of rough-surfaced endoplasmic reticulum arranged in the form of broad cisternae stacked one on top of the other.
Many of the ribosomes are attached to the surface of the endoplasmic reticulum. Since the ribosomes contain RNA, the Nissl substance is basophilic and can be well demonstrated by staining with toluidine blue or other basic aniline dyes and using the light microscope.
Functions of N issls substance The Nissl substance is responsible for synthesizing protein, which flows along the dendrites and the axon and replaces the proteins that are broken down during cellular activity .
Ribosomes Structure - Dot-like organelles attached to the rough ER or free in the cytosol Function(s) – Reads RNA to synthesize proteins
Rough Endoplasmic Reticulum Structure – a system of membranous tubes and sacs covered with dark dots ( ribosomes ) Function(s) - Makes alterations to proteins produced by ribosomes - Folds proteins into the correct shape
Smooth Endoplasmic Reticulum Structure - A system of membranous tubules and sacs Function(s) - helps move lipids, steroids, and fatty acids within the cell (intracellular highway); regulates calcium levels; breaks down toxic substances
Golgi complex The Golgi complex, when seen with the light microscope after staining with a silverosmium method , appears as a network of irregular wavy threads around the nucleus . In electron micrographs, it appears as clusters of flattened cisternae and small vesicles made up of smooth-surfaced endoplasmic reticulum.
Functions of G olgi complex The protein produced by the Nissl substance is transferred to the inside of the Golgi complex in transport vesicles, where it is temporarily stored. Golgi complex is specialized for different types of enzymatic reaction. At the trans side of the complex, the macromolecules are packaged in vesicles for transport to the nerve terminals. The Golgi complex is also thought to be active in lysosome production and in the synthesis of cell membranes.
Mitochondria Mitochondria are found scattered throughout the cell body, dendrites, and axons . They are spherical or rod shaped. In electron micrographs, the walls show a characteristic double membrane . The inner membrane is thrown into folds or cristae that project into the center of the mitochondrion. Mitochondria possess many enzymes , which are localized chiefly on the inner mitochondrial membrane. These enzymes take part in the tricarboxylic acid cycle and the cytochrome chains of respiration . Therefore , mitochondria are important in nerve cells, as in other cells, in the production of energy.
Mitochondria
Electron micrograph of a Neuron Nucleus & Number of cytoplasmic organelles
Neurofibrils Neurofibrils , as seen with the light microscope after staining with silver, are numerous and run parallel to each other through the cell body into the neurites . With the electron microscope, the neurofibrils may be resolved into bundles of Neurofilaments each filament measuring about 10 nm in diameter . The neurofilaments form the main component of the cytoskeleton.
Figure 2-13 Photomicrograph of a silver-stained section of a neuron showing the presence of large numbers of neurofibrils in the cytoplasm of the cell body and the neurites . Silver stained section of a Neuron showing presence of large numbers of neurofibrils in cytoplasm of the cell body & neurites
Microfilaments Microfilaments measure about 3 to 5 nm in diameter and are formed of actin . Microfilaments are concentrated at the periphery of the cytoplasm just beneath the plasma membrane where they form a dense network. Together with microtubules, microfilaments play a key role in the formation of new cell processes and the retraction of old ones. They also assist the microtubules in axon transport.
M icrotubules They measure about 25 nm in diameter and are found interspersed among the neurofilaments . They extend throughout the cell body and its processes The microtubules and the microfilaments provide a stationary track that permits specific organelles to move by molecular motors. They are responsible for cell transport.
Cell transport involves the movement of membrane organelles, secretory material, synaptic precursor membranes, large dense core vesicles, mitochondria, and smooth endoplasmic reticulum. Cell transport can take place in both directions in the cell body and its processes . It is of two kinds: rapid (100 to 400 mm per day) and slow (0.1 to 3.0 mm per day).
Rapid transport (100 to 400 mm per day) is brought about by two motor proteins associated with the microtubule adenosine triphosphate (ATP)- ase sites; Kinesin for anterograde (away from the cell) movement Dynein for retrograde movement.
Slow transport (0.1 to 3.0 mm per day) involves the bulk movement of the cytoplasm and includes the movement of mitochondria and other organelles. Slow axonal transport occurs only in the anterograde direction.
Electron micrograph of dentrites showing presence of neurofilament & microtubules within their cytoplasm (B) Transverse section of a dentrites (A) Longitudional section of two adjacent dentrites
Lysosomes Lysosomes are membrane-bound vesicles measuring about 8 nm in diameter. They serve the cell by acting as intracellular scavengers and contain hydrolytic enzymes. Lysosomes exist in three forms: (1) primary lysosomes , which have just been formed; ( 2) secondary lysosomes , which contain partially digested material (myelin figures ) ( 3) residual bodies, in which the enzymes are inactive and the bodies have evolved from digestible materials such as pigment and lipid. Digesting enzymes
Centrioles Structure - Cylindrical bodies that appear during cell division Function(s) – Help move DNA during division in animal cells Found In - Animal cells only
cell membrane cell boundary controls movement of materials in & out recognizes signals cytoplasm jelly-like material holding organelles in place vacuole & vesicles transport inside cells storage mitochondria make ATP energy from sugar + O 2 nucleus protects DNA controls cell ribosomes builds proteins ER helps finish proteins makes membranes Golgi apparatus finishes, packages & ships proteins lysosome food digestion garbage disposal & recycling
2) Plasma membrane It is the site for the initiation and conduction of the nerve impulse The plasma membrane is composed of an inner and an outer layer of very loosely arranged protein molecules separated by a middle layer of lipid . Certain protein molecules lie within the phospholipid layer and span the entire width of the lipid layer. These molecules provide the membrane with hydrophilic channels through which inorganic ions may enter and leave the cell.
Resting state
Excited state
Returns to resting state
Ion Channels and the AP
Properties of the Action Potential The action potential: Is an “all or none” event: membrane potential either passes threshold or doesn’t Is propagated down the axon membrane Has a fixed amplitude: AP’s don’t change in height to signal information ( nondegremental ) Has a conduction velocity (meters/sec) Has a refractory period in which stimulation will not produce an AP (limits the firing rate) .
Saltatory Conduction The “jumping” of an impulse between the “Nodes of Ranvier ” dramatically increasing it’s speed.
3) Nerve cell processes Dendrites Axons
Dendites The membrane of the neuron functions as a receptive surface over its entire extent; however, specific inputs (termed afferents) from other cells are received primarily on the surface of the cell body and on the surface of the specialized processes known as dendrites. The dendritic processes may branch extensively and are often covered with projections known as dendritic spines .
Spines provide a tremendous increase in the surface area available for synaptic contacts. Dendrites contain numerous orderly arrays of microtubules and fewer neurofilaments . The microtubule associated proteins (MAPs) in the dendrite have a higher molecular weight than those found in the axon. An example is MAP2.
Why do dendrites have so much branches? Dendrites provide an enlarged surface area to receive signals from the terminal buttons of other axons allowing for a chemical signal to pass simultaneously to many target cells.
Dendrites Figure :Diagrammatic representation of the neuron dendrite, emphasizing the areas of contact by other afferent inputs to the neuron.
Axon hillock The cone-shaped region of the cell body where the axon originates is termed the axonhillock . This area is free of ribosomes and most other cell organelles, with the exception of cytoskeletal elements and organelles that are being transported down the axon. The region between the axon hillock and the beginning of the myelin sheath is known as the initial segment . In many cases, this region is the anatomical location for the initiation of the action potential. .
Axons The other type of process in the idealized neuron is the axon. Each neuron has only one axon and it is usually straighter and smoother than the dendritic profiles. Axons also contain bundles of microtubules and neurofilaments and scattered mitochondria . Microfilaments within the axon are usually associated with an area adjacent to the plasmalemma and often are the most dense at the nodes of Ranvier . Axon Hillock Initial segment of axon Microtubules
The axon itself is often surrounded by a membranous material, called the myelin sheath, formed by glia cells. The myelin sheath acts to insulate the plasmalemma of the axon in a way that necessitates the more rapid spread of the depolarization of the plasmalemma and increases the speed of conduction of the nerve impulse. At the distal-most end of the axon and its collaterales are small branches whose tips are button-shaped cytoplasmic enlargements called terminal boutons or nerve endings
AXON vs DENDRITE AXON Only one axon is present in a neuron. It is a thin long process of uniform thickness and smooth surface. The branches of axon are fewer and at right angles to the axon. Axon contains neurofibrils and no Nissl’s granules. It forms the efferent component of the impulse. DENDRITE Dendrites are usually multiple in number in a neuron. These are short multiple processes. Their thickness diminishes as these divide repeatedly. The branches are studded with spiny projections. The dendrites branch profusely and are given off at acute angles. Dendrites contain both neurofibrils and Nissl’s granules. Dendrites form the afferent component of the impulse
Synapse
Synapse It is the site of interneuronal communication There is a physical gap between pre- and post-synaptic membranes. Presynaptic membrane is typically an axon and it contains Mitochondria that provide energy for axon functions Vesicles (round objects) that contain neurotransmitter Cisternae that are a part of the Golgi apparatus: recycle vesicles Postsynaptic membrane can be A dendrite ( axodendritic synapse) A cell body ( axosomatic synapse) Another axon ( axoaxonic synapse)
Most neurons make synaptic connection to 1000 or more neurons and receive upto 10,000 connections from other neurons.
Types of synapses There are two fundamentally different types of synapses: Electrical synapse Chemical synapse.
Electrical synapse In an electrical synapse , the presynaptic and postsynaptic cell membranes are connected by special channels called gap junctions that are capable of passing electric current, causing voltage changes in the presynaptic cell to induce voltage changes in the postsynaptic cell. The main advantage of an electrical synapse is the rapid transfer of signals from one cell to the next. They are rare in human CNS. They can be bidirectional while chemical synapse are unidirectional.
Chemical synapse In a chemical synapse , electrical activity in the presynaptic neuron is converted (via the activation of voltage-gated calcium channels ) into the release of a chemical called a neurotransmitter that binds to receptors located in the plasma membrane of the postsynaptic cell. The neurotransmitter may initiate an electrical response or a secondary messenger pathway that may either excite or inhibit the postsynaptic neuron.
Chemical synapses can be classified according to the neurotransmitter released: glutamatergic (often excitatory), GABAergic (often inhibitory), cholinergic (e.g. vertebrate neuromuscular junction ), and adrenergic (releasing norepinephrine ).
Neurotransmitter Release Vesicles lie “docked” near the presynaptic membrane The arrival of an action potential at the axon terminal opens voltage-dependent CA ++ channels CA ++ ions flow into the axon CA ++ ions change the structure of the proteins that bind the vesicles to the presynaptic membrane A fusion pore is opened, which results in the merging of the vesicular and presynaptic membranes The vesicles release their contents into the synapse Released transmitter then diffuses across cleft to interact with postsynaptic membrane receptors
81
Postsynaptic Receptors Molecules of neurotransmitter (NT) bind to receptors located on the postsynaptic membrane Receptor activation opens postsynaptic ion channels Ions flow through the membrane, producing either depolarization or hyperpolarization The resulting postsynaptic potential (PSP) depends on which ion channel is opened Postsynaptic receptors alter ion channels Directly ( ionotropic receptors) Indirectly, using second messenger systems that require energy ( metabotropic receptors)
Postsynaptic Potentials PSPs are either excitatory (EPSP) or inhibitory (IPSP) Opening NA + ion channels results in an EPSP Opening K + ion channels results in an IPSP PSPs are conducted down the neuron membrane Neural integration involves the algebraic summation of PSPs A predominance of EPSPs at the axon will result in an action potential If the summated PSPs do not drive the axon membrane past threshold, no action potential will occur
Neuromodulator Modulate and modify the activity of postsynaptic neuron They donot have direct effect rather they enhance, prolong and inhibit the effect of principal neurotransmitter on postsynaptic membrane. Act on G protein coupled receptors Ex. Acetycholine , serotonin, histamine and adenosine
Source of information Snells neuroanatomy Grays anatomy