ASSIGNMENT “PHYSIOLOGY” NEURONS AND DIFFERENT TYPES, CONDUCTIVITY OF IMPULSE SUBMITTED TO: MISS KALSOOM (LECTURER) THE UNIVERSITY OF LAHORE SUBMITTED BY: IRFAN AHMAD BS. BIOCHEMISTRY 1ST SMESTER BB-307-033 fani3264@gmail.com www.imbb07.wordpress.com 1 Neurons Neurons Neuron is unit of Nervous system. Neurons are typically composed of a soma, or cell body, a dendritic tree and an axon. The majority of vertebrate neurons receives input on the cell body and dendritic tree, and transmits output via the axon. However, there is great heterogeneity throughout the nervous system and the animal kingdom, in the size, shape, and function of neurons. Neurons are usually considered amitotic; however, recent research shows that they do indeed undergo adult neurogenesis. Neurons communicate via chemical and electrical synapses, in a process known as synaptic transmission. The fundamental process that triggers synaptic transmission is the action potential, a propagating electrical signal that is generated by exploiting the electrically excitable membrane of the neuron. This is also known as a wave of depolarization. History The neuron's place as the primary functional unit of the nervous system was first recognized in the early 20th century through the work of the Spanish anatomist Santiago Ramón y Cajal. Cajal proposed that neurons were discrete cells that communicated with each other via specialized junctions, or spaces, between cells. This became known as the neuron doctrine, one of the central tenets of modern neuroscience. To observe the structure of individual neurons, Cajal used a silver staining method developed by his rival, Camillo Golgi. The Golgi stain is an extremely useful method for neuroanatomical investigations because, for reasons unknown, it stains a very small percentage of cells in a tissue, so one is able to see the complete microstructure of individual neurons without much overlap from other cells in the densely packed brain. Anatomy and histology Neurons are highly specialized for the processing and transmission of cellular signals. Given the diversity of functions performed by neurons in different parts of the nervous system, there is, as expected, a wide variety in the shape, size, and electrochemical www.physiology033.wordpress.com 2 Neurons properties of neurons. For instance, the soma of a neuron can vary from 4 to 100 micrometers in diameter. The soma is the central part of the neuron. It contains the nucleus of the cell, and therefore is where most protein synthesis occurs. The nucleus ranges from 3 to 18 micrometers in diameter. The dendrites of a neuron are cellular extensions with many branches, and metaphorically this overall shape and structure is referred to as a dendritic tree. This is where the majority of input to the neuron occurs. Information outflow (i.e. from dendrites to other neurons) can also occur, but not across chemical synapses; there, the backflow of a nerve impulse is inhibited by the fact that an axon does not possess chemoreceptors and dendrites cannot secrete neurotransmitter chemicals. This unidirectionality of a chemical synapse explains why nerve impulses are conducted only in one direction. www.physiology033.wordpress.com 3 Neurons The axon is a finer, cable-like projection which can extend tens, hundreds, or even tens of thousands of times the diameter of the soma in length. The axon carries nerve signals away from the soma (and also carries some types of information back to it). Many neurons have only one axon, but this axon may - and usually will - undergo extensive branching, enabling communication with many target cells. The part of the axon where it emerges from the soma is called the 'axon hillock'. Besides being an anatomical structure, the axon hillock is also the part of the neuron that has the greatest density of voltage-dependent sodium channels. This makes it the most easily-excited part of the neuron and the spike initiation zone for the axon: in neurological terms it has the most negative hyperpolarized action potential threshold. While the axon and axon hillock are generally involved in information outflow, this region can also receive input from other neurons. The axon terminal contains synapses, specialized structures where neurotransmitter chemicals are released in order to communicate with target neurons. Although the canonical view of the neuron attributes dedicated functions to its various anatomical components, dendrites and axons often act in ways contrary to their so-called main function. Axons and dendrites in the central nervous system are typically only about one micrometer thick, while some in the peripheral nervous system are much thicker. The soma is usually about 10–25 micrometers in diameter and often is not much larger than the cell nucleus it contains. The longest axon of a human motoneuron can be over a meter long, reaching from the base of the spine to the toes. Sensory neurons have axons that run from the toes to the dorsal columns, over 1.5 meters in adults. Giraffes have single axons several meters in length running along the entire length of their necks. Much of what is known about axonal function comes from studying the squid giant axon, an ideal experimental preparation because of its relatively immense size (0.5–1 millimeters thick, several centimeters long). www.physiology033.wordpress.com 4 Neurons Types of Neurons 1) Sensory Neurons 2) Accessory Neurons 3) Motor Neurons Sensory neurons are nerve cells within the nervous system responsible for converting external stimuli from the organism's environment into internal electrical motor reflex loops and several forms of involuntary behavior, including pain avoidance. In humans, such reflex circuits are commonly located in the spinal cord. In complex organisms, sensory neurons relay their information to the central nervous system or in less complex organisms, such as the hydra, directly to motor neurons and sensory neurons also transmit information to the brain, where it can be further processed and acted upon. For example, olfactory sensory neurons make synapses with neurons of the olfactory bulb, where the sense of olfaction (smell) is processed. At the molecular level, sensory receptors located on the cell membrane of sensory neurons are responsible for the conversion of stimuli into electrical impulses. The type of receptor employed by a given sensory neuron determines the type of stimuli it will be sensitive to. For example, neurons containing mechanoreceptors are sensitive to tactile stimuli, while olfactory receptors make a cell sensitive to odors. Associate neurons An interneuron (also called relay neuron, association neuron or bipolar neuron) is a term used to describe a neuron which has two different common meanings. PNS In the peripheral nervous system, an interneuron is a neuron that communicates only to other neurons. Interneurons are the neurons that provide connections between sensory www.physiology033.wordpress.com 5 Neurons and motor neurons, as well as between themselves. Contrast to sensory neurons or motor neurons, which respectively provide input from and output to the rest of the body. CNS According to the PNS definition, the neurons of the central nervous system, including the brain, are all interneurons. However, in the CNS, the term interneurons is also used for the general group of small, locally projecting neurons of the central nervous system. These neurons are typically inhibitory, and use the neurotransmitter GABA or glycine. However, excitatory interneurons using glutamate also exist as do interneurons releasing neuromodulators like acetylcholine. A human brain contains about 100 billion interneurons. An example of interneurons are inhibitory interneurons in the neocortex which selectively inhibit sections of the thalamus based on synaptic input both from other parts of the neocortex and from the thalamus itself. This is theorized to help focus higher attention on relevant sensory input and help block out behavioraly irrelevant or unchanging input, such as the sensation of the backs of your thighs on a chair. The neurophysiological measure short-latency intracortical inhibition (SICI) is believed to be mediated by these inhibitory interneurons. Spinal interneurons 1a Inhibitory Neuron: Found in Lamina VII. Responsible for inhibiting antagonist motor neuron. 1a spindle afferents activate 1a inhibitory neuron. 1b Inhibitory Neuron: Found in Lamina V, VI, VII. 1b afferent or golgi tendon organ activates it. Cortical interneurons Parvalbumin-containing interneurons CCK-containing interneurons VIP-containing interneurons www.physiology033.wordpress.com 6 Neurons Cerebellar interneurons Molecular layer interneurons (basket cells, stellate cells) Golgi cells Granule cells Motor neuron Motor neuron Section through the spinal cord. Motor neuron projection through ventral root is shown in red. In vertebrates, the term motor neuron (or motoneuron) classically applies to neurons located in the central nervous system (CNS) that project their axons outside the CNS and directly or indirectly control muscles. Motor neuron is often synonymous with efferent neuron. Upper motor neuron Upper motor neurons are motor neurons that originate in motor region of the cerebral cortex or the brain stem and carry motor information down to the final common pathway, that is, any motor neurons that are not directly responsible for stimulating the target muscle. The main effector neurons for voluntary movement lie within layer V of the primary motor cortex and are called Betz cells. The cell bodies of these neurons are some of the largest in the brain, approaching nearly 100μm in diameter. These neurons connect the brain to the appropriate level in the spinal cord, from which point nerve signals continue to the muscles by means of the lower motor neurons. The www.physiology033.wordpress.com 7 Neurons neurotransmitter glutamate transmits the nerve impulses from upper to lower motor neurons where it is detected by glutamatergic receptors. Lower motor neuron Lower motor neurons (LMNs) are the motor neurons connecting the brainstem and spinal cord to muscle fibers, bringing the nerve impulses from the upper motor neurons out to the muscles. The lower motor neuron's axon goes through a foramen and terminates on an effector (muscle). Classification The axons of lower motor neurons are a type of motor fibers. Lower motor neurons are classified based on the type of muscle fiber they innervate: Alpha motor neurons (α-MNs) innervate extrafusal muscle fibers, the most numerous type of muscle fiber and the one most involved in muscle contraction. Gamma motor neurons (γ-MNs) innervate intrafusal muscle fibers, which are involved with muscle spindles and the sense of body position. Structural classification Polarity Most neurons can be anatomically characterized as: Unipolar or pseudounipolar: dendrite and axon emerging from same process. www.physiology033.wordpress.com 8 Bipolar: axon and single dendrite on opposite ends of the soma. Multipolar: more than two dendrites: o Neurons Golgi I: neurons with long-projecting axonal processes; examples are pyramidal cells, Purkinje cells, and anterior horn cells. o Golgi II: neurons whose axonal process projects locally; the best example are the granule cells. Other Furthermore, some unique neuronal types can be identified according to their location in the nervous system and distinct shape. Some examples are: Basket cells, neurons with dilated and knotty dendrites in the cerebellum. Betz cells, large motor neurons. Medium spiny neurons, most neurons in the corpus striatum. Purkinje cells, huge neurons in the cerebellum, a type of Golgi I multipolar neuron. pyramidal cells, neurons with triangular soma, a type of Golgi I. Renshaw cells, neurons with both ends linked to alpha motor neurons. Granule cells, a type of as Golgi II neuron. anterior horn cells, motoneurons located in the spinal cord. Functional classification Direction Afferent neurons convey information from tissues and organs into the central nervous system and are sometimes also called sensory neurons. Efferent neurons transmit signals from the central nervous system to the effector cells and are sometimes called motor neurons. www.physiology033.wordpress.com 9 Neurons Interneurons connect neurons within specific regions of the central nervous system. Afferent and efferent can also refer generally to neurons which, respectively, bring information to or send information from the brain region. Afferent nerve In the nervous system, afferent neurons--otherwise known as sensory or receptor neurons--carry nerve impulses from receptors or sense organs toward the central nervous system. This is the case vice versa as well. This term can also be used to describe relative connections between structures. Afferent neurons communicate with specialized interneurons. (The opposite activity of direction or flow is efferent.) In the nervous system there is a "closed loop" system of sensation, decision, and reactions. This process is carried out through the activity of afferent neurons, interneurons, and efferent neurons. A touch or painful stimulus, for example, creates a sensation in the brain only after information about the stimulus travels there via afferent nerve pathways. Afferent neurons are pseudounipolar neurons, that have a single long dendrite and a short axon, and a smooth and rounded cell body. The dendrite is structurally and functionally similar to an axon, and is myelinated; it is these axon-like dendrites that make up the afferent nerves. Just outside the spinal cord, thousands of afferent neuronal cell bodies are aggregated in a swelling in the dorsal root known as the dorsal root ganglion. Efferent nerve In the nervous system, efferent nerves – otherwise known as motor or effector neurons – carry nerve impulses away from the central nervous system to effectors such as muscles or glands (and also the ciliated cells of the inner ear). The term can also be used to describe relative connections between nervous structures. The opposite activity of direction or flow is afferent. www.physiology033.wordpress.com 10 Neurons The motor nerves are efferent nerves involved in muscular control. The cell body of the efferent neuron is found in the central nervous system where it is connected to a single, long axon and several short dendrites projecting out of the cell body itself. This axon then forms a neuromuscular junction with the effectors. The cell body of the motor neuron is satellite-shaped. The motor neuron is present in the grey matter of the spinal cord and medulla oblongata, and forms an electrochemical pathway to the effector organ or muscle. Action on other neurons Excitatory neurons excite their target neurons. Excitatory neurons in the central nervous system, including the brain, are often glutamatergic. Neurons of the peripheral nervous system, such as spinal motoneurons that synapse onto muscle cells, often use acetylcholine as their excitatory neurotransmitter. However, this is just a general tendency that is not always true. It is not the neurotransmitter that decides excitatory or inhibitory action, but rather it is the postsynaptic receptor that is responsible for the action of the neurotransmitter. Inhibitory neurons inhibit their target neurons. Inhibitory neurons are often interneurons. The output of some brain structures (neostriatum, globus pallidus, cerebellum) are inhibitory. The primary inhibitory neurotransmitters are GABA and glycine. Modulatory neurons evoke more complex effects termed neuromodulation. These neurons use such neurotransmitters as dopamine, acetylcholine, serotonin and others. Discharge patterns Neurons can be classified according to their electrophysiological characteristics: Tonic or regular spiking. Some neurons are typically constantly (or tonically) active. Example: interneurons in neurostriatum. Phasic or bursting. Neurons that fire in bursts are called phasic. www.physiology033.wordpress.com 11 Neurons Fast spiking. Some neurons are notable for their fast firing rates, for example some types of cortical inhibitory interneurons, cells in globus pallidus. Thin-spike. Action potentials of some neurons are more narrow compared to the others. For example, interneurons in prefrontal cortex are thin-spike neurons. Neurotransmitter released Some examples are cholinergic neurons GABAergic neurons glutamatergic neurons dopaminergic neurons 5-hydroxytryptamine neurons (5-HT; serotonin) Connectivity Synapse Neurons communicate with one another via synapses, where the axon terminal of one cell impinges upon a dendrite or soma of another (or less commonly to an axon). Neurons such as Purkinje cells in the cerebellum can have over 1000 dendritic branches, making connections with tens of thousands of other cells; other neurons, such as the magnocellular neurons of the supraoptic nucleus, have only one or two dendrites, each of which receives thousands of synapses. Synapses can be excitatory or inhibitory and will either increase or decrease activity in the target neuron. Some neurons also communicate via electrical synapses, which are direct, electrically-conductive junctions between cells. In a chemical synapse, the process of synaptic transmission is as follows: when an action potential reaches the axon terminal, it opens voltage-gated calcium channels, allowing calcium ions to enter the terminal. Calcium causes synaptic vesicles filled with neurotransmitter molecules to fuse with the membrane, releasing their contents into the www.physiology033.wordpress.com 12 Neurons synaptic cleft. The neurotransmitters diffuse across the synaptic cleft and activate receptors on the postsynaptic neuron. The human brain has a huge number of synapses. Each of the 1011 (one hundred billion) neurons has on average 7,000 synaptic connections to other neurons. It has been estimated that the brain of a three-year-old child has about 1016 synapses (10 quadrillion). This number declines with age, stabilizing by adulthood. Estimates vary for an adult, ranging from 1015 to 5 x 1015 synapses (1 to 5 quadrillion). Mechanisms for propagating action potentials The cell membrane in the axon and soma contain voltage-gated ion channels which allow the neuron to generate and propagate an electrical impulse (an action potential). Substantial early knowledge of neuron electrical activity came from experiments with squid giant axons. In 1937, John Zachary Young suggested that the giant squid axon can be used to study neuronal electrical properties. As they are much larger than human neurons, but similar in nature, it was easier to study them with the technology of that time. By inserting electrodes into the giant squid axons, accurate measurements could be made of the membrane potential. Electrical activity can be produced in neurons by a number of stimuli. Pressure, stretch, chemical transmitters, and electrical current passing across the nerve membrane as a result of a difference in voltage can all initiate nerve activity. The narrow cross-section of axons lessens the metabolic expense of carrying action potentials, but thicker axons convey impulses more rapidly. To minimize metabolic expense while maintaining rapid conduction, many neurons have insulating sheaths of myelin around their axons. The sheaths are formed by glial cells: oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. The sheath enables action potentials to travel faster than in unmyelinated axons of the same diameter, whilst using less energy. The myelin sheath in peripheral nerves normally runs along the axon in sections about 1 mm long, punctuated by unsheathed nodes of Ranvier which www.physiology033.wordpress.com 13 Neurons contain a high density of voltage-gated ion channels. Multiple sclerosis is a neurological disorder that results from demyelination of axons in the central nervous system. Some neurons do not generate action potentials, but instead generate a graded electrical signal, which in turn causes graded neurotransmitter release. Such nonspiking neurons tend to be sensory neurons or interneurons, because they cannot carry signals long distances. Histology and internal structure Nerve cell bodies stained with basophilic dyes show numerous microscopic clumps of Nissl substance (named after German psychiatrist and neuropathologist Franz Nissl, 1860–1919), which consists of rough endoplasmic reticulum and associated ribosomes. 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). There are different internal structural characteristics between axons and dendrites. Axons typically almost never contain ribosomes, except some in the initial segment. Dendrites contain granular endoplasmic reticulum or ribosomes, with diminishing amounts with distance from the cell body. The neuron doctrine The neuron doctrine is the now fundamental idea that neurons are the basic structural and functional units of the nervous system. The theory was put forward by Santiago Ramón y Cajal in the late 19th century. It held that neurons are discrete cells (not connected in a meshwork), acting as metabolically distinct units. Cajal further extended this to the Law of Dynamic Polarization, which states that neural transmission goes only in one direction, from dendrites toward axons. As with all doctrines, there are some exceptions. For example glial cells may also play a role in information processing. Also, www.physiology033.wordpress.com 14 Neurons electrical synapses are more common than previously thought, meaning that there are direct-cytoplasmic connections between neurons. In fact, there are examples of neurons forming even tighter coupling; the squid giant axon arises from the fusion of multiple neurons that retain individual cell bodies and the crayfish giant axon consists of a series of neurons with high conductance septate junctions. The Law of Dynamic Polarization also has important exceptions; dendrites can serve as synaptic output sites of neurons. And axons can receive synaptic inputs. Neurons in the brain The number of neurons in the brain varies dramatically from species to species. One estimate puts the human brain at about 100 billion (1011) neurons and 100 trillion (1014) synapses. By contrast, the nematode worm Caenorhabditis elegans has just 302 neurons making it an ideal experimental subject as scientists have been able to map all of the organism's neurons. By contrast, the fruit fly Drosophila melanogaster has around 300,000 neurons (which do spike) and exhibits many complex behaviors. Many properties of neurons, from the type of neurotransmitters used to ion channel composition, are maintained across species, allowing scientists to study processes occurring in more complex organisms in much simpler experimental systems. How do neurons communicate with each other? 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). Now, 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 pre-synaptic 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 www.physiology033.wordpress.com 15 Neurons 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. Synaptic transmission can be excitatory or inhibitory Neurotransmission excitatory, i.e. can it be increases either the possibility of the post-synaptic neuron firing an action potential, or inhibitory. In this case, the inhibitory signal reduces the likelihood of an action potential being generated following excitation. So how does inhibition work? Well, this is where things get a little more complicated! We have seen that the action potential is propagated by the leading edge of a depolarization wave activating sodium channels further down the axon. We have also seen that the activation of these sodium channels is achieved by a small depolarization the of neuronal membrane. But what happen would if the membrane potential was stabilised? The depolarisation inside the neuronal axon would dissapate and the action potential would not be able to propagate any further - i.e. it would be inhibited. How, what, where, I hear you ask? The stabilisation of the membrane potential is achieved by an influx of negatively charged chloride ions that is unaffected by the www.physiology033.wordpress.com 16 Neurons depolarisation wave coming down the axon. Formerly, this is equivalent to an efflux of positively charged sodium ions. Thus it is like punching a hole in a hose so that water will leak out through the puncture and not get to the sprinkler! Chemical synapses Are specialized junctions through whom the cells of the nervous system signal to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow the neurons of the central nervous system to form interconnected neural circuits. They are thus crucial to the biological computations that underlie perception and thought. They provide the means through which the nervous system connects to and controls the other systems of the body. A chemical synapse between a motor neuron and a muscle cell is called a neuromuscular junction; this type of synapse is well-understood. The human brain contains a huge number of chemical synapses; young children have about 1016 synapses (10 quadrillion). This number declines with age, stabilizing by adulthood. Estimates for adults vary from 1015 to 5 × 1015 (1-5 quadrillion) synapses. The word "synapse" comes from "synaptein", which Sir Charles Scott Sherrington and his colleagues coined from the Greek "syn-" ("together") and "haptein" ("to clasp"). Chemical synapses are not the only type of biological synapse: electrical and immunological synapses exist as well. Without a qualifier, however, "synapse" commonly refers to a chemical synapse. The signal across a synapse may be regarded as neurocrine, analogous to the types of signaling of the endocrine system (endocrine, paracrine and autocrine). www.physiology033.wordpress.com 17 Neurons References 1):- López-Muñoz, F.; Boya, J., Alamo, C. (16 October 2006). "Neuron theory, the cornerstone of neuroscience, on the centenary of the Nobel Prize award to Santiago Ramón y Cajal". Brain Research Bulletin 70: 391–405. doi:doi:10.1016/j.brainresbull.2006.07.010. PMID 17027775. Retrieved on 2007-04-02. 2):- Grant, Gunnar (9 January 2007 (online)). "How the 1906 Nobel Prize in Physiology or Medicine was shared between Golgi and Cajal". Brain Research Reviews. doi:doi:10.1016/j.brainresrev.2006.11.004. PMID 17027775. Retrieved on 2007-04-02. www.physiology033.wordpress.com