Biopsychology Unit 2: Neuron PDF

Biopsychology UNIT 2: Neuron Structure and Functions of Neurons; Action Potential/ Nerve Impulse; Synaptic Transmission  Chapter Outline ▪ Basic Structure of a Neuron ▪ Internal Structure of a Neuron ▪ Types and Functions of Neurons ▪ Supporting Cells of the Nervous System ▪ Communicat...

Biopsychology UNIT 2: Neuron Structure and Functions of Neurons; Action Potential/ Nerve Impulse; Synaptic Transmission  Chapter Outline ▪ Basic Structure of a Neuron ▪ Internal Structure of a Neuron ▪ Types and Functions of Neurons ▪ Supporting Cells of the Nervous System ▪ Communication within a Neuron: Action Potential/Nerve Impulse ▪ Communication between Neurons: Synaptic Transmission  Neuron ▪ Our behaviour depends on the integration of numerous processes within the body. This integration is provided by the nervous system with the help of endocrine glands. ▪ The nervous system is made up of billions of specialized, mutually communicating cells called neurons. ▪ Neuron is the basic functional unit of the nervous system. It is a “miniature self-contained information processor” that is specialized for the reception, conduction, and transmission of electrochemical signals. ▪ In vertebrate animals, neurons are the core components of the brain, spinal cord and peripheral nerves.  Fun Facts about Neurons Some interesting statistics about neurons in humans (remember that these are averages because there is a lot of variability in the nervous system!): ▪ Average number of neurons in the human brain = 100 billion (about as many neurons as there are stars in the Milky Way). Note: One billion has 9 zeros and it looks like: 1,000,000,000! ▪ Each individual neuron can form thousands of links with other neurons, giving a typical brain well over 100 trillion synapses (up to 1,000 by some estimates) Note: One trillion has 12 zeros, and it looks like this: 1,000,000,000,000!  Fun Facts about Neurons ▪ Rate of neuron growth during fetal development throughout the course of pregnancy = 250,000 neurons/minute ▪ Diameter of a neuron = 4 microns (granule cell) to 100 microns (motor neuron in spinal cord) (1 micron= one-thousandth of a millimeter) ▪ Velocity of signal transmitted through a neuron = 1.2 to 250 miles/hour.  Fun Facts about Neurons What if we lined up all the neurons in our body? How long would that line stretch? Let’s assume that one neuron is about 10 microns long (Remember, this is just an example, because neurons come in all different sizes). So, if we line up 100 billion neurons which are 10 microns long… 100,000,000,000 neurons x 10 microns = 1,000 km or about 600 miles! Note: 1,000 microns (micrometer) = 1 millimeter (mm) 10 mm = 1 centimeter (cm) 100 cm = 1 meter (m) 1,000 m = 1 kilometer (km) Basic Structure of a Neuron Basic Structure of a Neuron  Basic Structure of a Neuron Neurons come in an incredibly variety of shapes and sizes; however, most of them have the following four structures: Cell body, or soma ▪ The neural cell body is the major biosynthetic center that provides for the life processes of the neuron. It has a single, centrally located nucleus that contains the nucleolus and chromosomes, necessary for the coded production of proteins within the cell. ▪ Its cytoplasm contains mitochondria, lysosomes, Golgi complex, an extensive endoplasmic reticulum and numerous inclusions.  Basic Structure of a Neuron Dendrites ▪ Dendrites are a vast number of short processes that branch extensively from the cell body. The branches increase in thickness as they coalesce and approach the cell body. ▪ The term dendrite comes from the Greek dendron, meaning “tree”, and the overall shape and structure of a neuron’s dendrites is called its dendritic tree. ▪ Along with the cell body, the dendrites serve as locations at which information from other neurons is received.  Basic Structure of a Neuron ▪ The dendrite’s surface is lined with specialized synaptic receptors, at which the dendrite receives information from other neurons. ▪ The greater the surface area of a dendrite, the larger the number of connections or synapses it can form with other neurons. ▪ Some dendrites branch widely and therefore have a large surface area. ▪ Some also contain dendritic spines, the short bud-like outgrowths that increase the surface area available for synapses.  Basic Structure of a Neuron ▪ The shape of dendrites varies enormously from one neuron to another and can even vary from one time to another for a given neuron. ▪ Because of the essential role that dendrites play in learning and memory, abnormal dendritic spines are an underlying cause of some types of human mental retardation.  Basic Structure of a Neuron Axon ▪ The axon is a long, slender cytoplasmic process capable of propagating a nerve impulse from the cell body to the terminal buttons. It is responsible for carrying neural messages to other neurons. ▪ Its diameter varies from a micrometer in certain nerves of the human brain to a millimeter in the giant fiber of the squid. ▪ It is cylindrical and relatively unbranched for most of its length, although it may give rise to a few branches called axon collaterals along the way.  Basic Structure of a Neuron ▪ The cone-shaped segment of axon that lies at the junction of the axon and the cell body is known as the axon hillock. Action potentials arise in the axon hillock and are then transmitted down the length of the axon. ▪ Many, but not all, axons in vertebrate nervous systems are covered by myelin sheath. It is a concentrically laminated fatty insulation layer that boosts the speed and efficiency of electrical signaling. (Amazingly, a large myelinated axon may have up to 250-300 turns of myelin wrapping around it!)  Basic Structure of a Neuron ▪ Myelin does not cover the entire length of an axon. The axon hillock is completely uncovered and between each myelin segment, there is a bare space of axon membrane known as a node of Ranvier. At these nodes (1-2 μm) , the axon is exposed to the extracellular space. ▪ Nodes of Ranvier occur somewhere between 0.2 mm to 2.0 mm apart down the length of the axon, depending on both the diameter and length of the axon. ▪ Large diameter axons have thicker myelin and greater distances between nodes of Ranvier.  Basic Structure of a Neuron There are important advantages to myelin: ▪ Myelin allows human axons to be smaller in diameter without sacrificing transmission speed. The smaller the diameter of our axons, the more neural tissue we can pack into our skulls, and the more information we can process. ▪ Myelin reduces the energy requirements of neurons by decreasing the amount of work done by sodium-potassium pumps.  Basic Structure of a Neuron Myelin is formed by certain types of glia that wrap themselves or their branches around segments of axon. ▪ Schwann cells make myelin in the peripheral nervous system (PNS). ▪ One Schwann cell forms a single myelin sheath.  Basic Structure of a Neuron ▪ Oligodendrocytes make myelin in the central nervous system (CNS). ▪ The oligodendrocyte sends cell processes to myelinate multiple segments on many axons.  Basic Structure of a Neuron Terminal button/ Synaptic knob ▪ The ends of many axons and its collaterals are divided into an extensive complex of fine terminal extensions, known as terminal arborizations or telodendria. As a result, a neuron with only one axon may still communicate with a large number of other cells. ▪ At the very end of each terminal arborization is a swelling, or a knob-like structure known as the terminal button/ synaptic knob/ axon terminal.  Basic Structure of a Neuron ▪ The terminal button has a large number of synaptic vesicles that contain neurotransmitters, the chemical messengers that have an excitatory or inhibitory effect on another neuron.  Basic Structure of a Neuron ▪ The messages that pass from one neuron to another are transmitted across the synapse, a junction between the terminal buttons of the sending cell and a portion of the somatic or dendritic membrane of the receiving cell. ▪ A neuron may receive information from dozens or even hundreds of neurons, each of which can form a large number of synaptic connections with it.  Basic Structure of a Neuron ▪ At each synapse, special ion channels serving as receptor sites are embedded in the neural membrane. ▪ These receptor sites interact with molecules of neurotransmitter released by adjacent neurons that float across the synaptic gap/ synaptic cleft, a fluid-filled space between the transmitting and receiving neurons.  Basic Structure of a Neuron Although all neurons have these general features, they vary greatly in size and shape. ▪ A neuron in the spinal cord may have an axon 3 to 4 feet long, running from the end of the spine to the muscles of the toe. ▪ A neuron in the brain may cover only a few thousandths of an inch. Internal Structure of a Neuron The Soma  The Soma ▪ The cell is filled with cytoplasm, a viscous semi-liquid substance that contains specialized structures. ▪ The most prominent structure is the nucleus, which contains the DNA that directs the cell’s functions. ▪ The nucleus also contains a substructure, known as the nucleolus. The nucleolus builds organelles known as ribosomes, which engage in protein synthesis.  The Soma ▪ The ribosomes produce proteins either on their own or in association with the endoplasmic reticulum, another small structure, or organelle, located in the cell body.  The Soma ▪ The endoplasmic reticulum may be divided into rough and smooth portions. ▪ The rough endoplasmic reticulum has many ribosomes bound to its surface, giving it the bumpy appearance responsible for its name. ▪ There are no ribosomes attached to the smooth endoplasmic reticulum.  The Soma ▪ After proteins are constructed by the ribosomes on the RER, they are moved by the SER to the Golgi apparatus. ▪ Golgi apparatus is a stack of membrane-enclosed disks that lie farthest from the nucleus. It sorts and packages newly synthesized proteins into vesicles for delivery to different parts of the neuron.  The Soma ▪ Mitochondria is the “power house” of the cell. It breaks down glucose, produces adenosine triphosphate (ATP). The chemical energy stored in the ATP is used to used to fuel most of the biochemical reactions of the neuron. ▪ Lysosomes are a concentrative mixture of degradative enzymes that are used for lifelong recycling of biomolecules and organelles. The Cell Membrane The Cell Membrane ▪ The cell membrane is a double layer of phospholipid molecules that defines the boundary of the cell and separates the intracellular and extracellular fluids. ▪ Suspended within the phospholipid membrane are a number of protein structures that control its permeability, the movement of substances across the cell membrane. The Cell Membrane ▪ Two types of protein structures of primary importance are: ion pumps and ion channels. These structures provide pores, or channels through which specific ions, or electrically charged particles, can move into or out of the neuron. ▪ Ion pumps (such as the sodium-potassium pump, calcium pump) use energy to move ions in and out of the cell. ▪ Ion channels allow ions to move passively without the expenditure of energy. The Cell Membrane ▪ Voltage-dependent ion channels open and close in response to the electrical status of adjacent areas of membrane, and play an important role in electrical signaling within the neuron. ▪ Ligand-gated ion channels open when they come in contact with specific chemicals, and are important for events taking place at the synapse. The Cell Membrane The cell membrane is important for several reasons: ▪ It controls the movement of ions that directly affect nerve signaling. ▪ It is the site of the electrical activity that is the basis of nerve impulse. ▪ It is the site of the action of peptides and hormones. ▪ It provides the sites for synapses where signals are transmitted from one neuron to another. The Cytoskeleton The cytoskeleton is a matrix of protein strands, linked to each other that forms a cohesive mass and gives a cell its shape. Three types of filament, or fibers, make up the neural cytoskeleton. The Cytoskeleton ▪ Microtubules are formed in the shape of hollow tubes with a diameter of about 25nm*.They are responsible for the movement of various materials within the cell. ▪ Movement along the microtubules from the cell body to the axon terminal is known as anterograde axoplasmic transport. ▪ Movement back to the cell body from the periphery of the neuron is known as retrograde axoplasmic transport. *One 1000th of a micrometer is a nanometer, or nm The Cytoskeleton ▪ Neurofilaments are usually about 10nm in diameter, and are quite strong for their size. They run parallel to the length of the axon and provide structural support. ▪ Microfilaments are the smallest fibers and range from 3 to 5 nm in diameter. Because most of the microfilaments are located in the branches of the neuron, they may participate in changing the shape and length of these structures during development and in response to learning.  Types of Neurons: Functional Classification ▪ Sensory (afferent) neurons: Are specialized to receive information about what’s going on inside and outside the body and transmit it to the central nervous system. ▪ The stimulus can come from exteroreceptors outside the body, for example light and sound, or from interoreceptors inside the body, for example blood pressure or the sense of body position. Types of Neurons: Functional Classification ▪ Sensory neurons are highly specialized receptors that translate many types of information, such as light or sound waves, into neural signals that the central nervous system can process. ▪ It is the sensory neurons that begin the process of sensation and perception. ▪ Sensory neurons can be unipolar or bipolar.  Types of Neurons: Functional Classification ▪ Motor (efferent) neurons: Transmit commands from the central nervous system to muscles, glands and organs throughout the body, thereby directly governing the behavior of the organism. ▪ Motor neurons have the most common type of ‘body plan’ for a nerve cell - they are multipolar, each with one axon and several dendrites.  Types of Neurons: Functional Classification ▪ Interneurons: Allow sensory and motor neurons to communicate with each other. As well as transferring signals between sensory and motor neurons, interneurons can also communicate with each other, forming circuits of various complexity. ▪ They constitute the bulk of the human nervous system and are involved in processing information, both in simple reflex circuits (like those triggered by hot objects) and in more complex functions such as learning and decision-making. ▪ They are multipolar, just like motor neurons, and are easily recognizable by their short axons. Types of Neurons: Functional Classification A simple Reflex Arc illustrates how these three types of neurons might work together.  Types of Neurons: Structural Classification ▪ Unipolar neurons have a single branch that extends from the cell body and then splits into two branches a short distance away. ▪ These neurons are typical of invertebrate nervous systems.  Types of Neurons: Structural Classification ▪ In vertebrates, unipolar cells are found in the sensory systems such as the somatosenses where they detect touch, pain, temperature changes and other sensory events that affect the skin. ▪ They are also found in the ANS where they detect events in the internal organs. ▪ Other unipolar neurons detects events in our joints, muscles.  Types of Neurons: Structural Classification ▪ Bipolar neurons – have two branches extending from the cell body at opposite ends: one axon and one dendrite. ▪ They play important roles in sensory systems of vision and audition. ▪ An example of a bipolar neuron is a retinal bipolar cell, which receives signals from photoreceptor cells that are sensitive to light and transmits these signals to ganglion cells that carry the signal to the brain.  Types of Neurons: Structural Classification ▪ Multipolar neurons – have many branches extending from the cell body, usually one axon and numerous dendrites. ▪ It is the most common structural type of neuron in the vertebrate nervous system, found throughout the CNS. ▪ The axons of these neurons make up the tracts of the brain and the motor nerves that extend from the CNS to the muscles.  Types of Neurons: Structural Classification ▪ On the basis of axonal length, multipolar neurons can be categorized into: Golgi type I (projection neuron), with long axons projecting to distant parts of the CNS, and Golgi type II (local circuit neuron), possessing short axons that establish contacts with local neighbouring neurons. ▪ Projection neurons, with their long axons, usually have large cell bodies. The local circuit neurons, with their short dendrites and small axons, usually have small, compact cell bodies.  Types of Neurons: Structural Classification Multipolar neurons can also be classified on the basis of their dendritic branching pattern and shape of the soma and include pyramidal, Purkinje, stellate cells etc. ▪ Pyramidal cells in the cerebral cortex and the hippocampus have cell bodies that are shaped like pyramids. They are excitatory neurons that have numerous apical and basal dendrites and a single axon that projects out of the cortex. ▪ Pyramidal cells are particularly prominent in motor and premotor areas.  Types of Neurons: Structural Classification ▪ The Purkinje cells of the cerebellum have dramatic dendritic trees that allow a single cell to form as many as 150,000 synapses. ▪ Stellate cells are star-shaped multipolar neurons that have short axons and make local synaptic contacts, tending to be enriched in sensory cortices. They are much smaller than pyramidal cells, and may be excitatory or inhibitory. Types of Neurons Types of Neurons  Neurons and Neuroanatomical Structure ▪ In general, there are two kinds of gross neural structures in the nervous system: those composed primarily of cell bodies and those composed primarily of axons. ▪ In the central nervous system, clusters of cell bodies are called nuclei (singular nucleus); in the peripheral nervous system, they are called ganglia (singular ganglion). ▪ In the central nervous system, bundles of axons are called tracts; in the peripheral nervous system, they are called nerves.  Functions of Neurons ▪ Receive and integrate inputs: The soma and dendrites form the somatodendritic zone, which receives a wide variety of signals from other neurons. The somatic zone also serves as a chemical integrator of incoming information. ▪ Generate a nerve impulse - The initial segment of the axon, the axon hillock, serves as an electrical integrator, and controls the firing of the neuron. If the total strength of the signal exceeds the threshold limit of the axon hillock, the structure will fire a signal (known as an action potential) down the axon, generating a nerve impulse in response to incoming electrical information.  Functions of Neurons ▪ Conduct electrical and chemical signals - The axon propagates the nerve impulse, with electrical signals traveling along the membrane of the axon and chemical signals traveling within its internal structural matrix. ▪ Transmit information to target cell (neuron, muscle, gland) - The presynaptic zone at the end of the axon contains unique structures that convert chemical and electrical signals into signal output which is transmitted to other neurons, muscles or glands.  Conducts action potential Axon hillock Generates action potential Receive and integrate inputs Transmits to target cell Supporting Cells of the Nervous System Neuroglia or glia (nerve glue) do not conduct impulses but provide the neurons with mechanical and metabolic support. There are five to ten times as many glia as neurons in the CNS. They perform the following functions: ▪ Physically and chemically insulate neurons from the rest of the environment. ▪ Lend structural support (particularly to axons). ▪ Supply important nutrients that neurons require. ▪ Destroy/digest dead neurons in a process called phagocytosis. Supporting Cells of the Nervous System Type Location Function Astrocyte Central nervous system Structural and nutritional support to neurons Blood-brain barrier Isolation of the synapse Regulation of chemical and ionic environment Debris cleanup Oligodendrocyte Central nervous system Myelination of axons Schwann Cell Peripheral nervous Myelination of axons system Microglia Central nervous system Debris cleanup Brain immune function Supporting Cells of the Nervous System Astrocyte Supporting Cells of the Nervous System Astrocyte: ▪ Astrocytes are large star-shaped glial cells of the CNS. ▪ They are the most common type of glia in the brain. ▪ Provide a structural matrix for the neurons. Form connections with the blood supply of the brain and transfer ▪ nutrients to the neurons. Along with the tissue that makes up the blood vessels, they form a ▪ blood-brain barrier which protects the neurons. Supporting Cells of the Nervous System Astrocyte: ▪ Surround and isolate the synapse, keeping the neurotransmitters from moving outside a restricted area. ▪ Control the chemical composition of the fluid surrounding neurons by actively taking up or releasing substances whose concentration must be kept at critical levels. ▪ Clean up debris within the brain by digesting dead neurons. Supporting Cells of the Nervous System Oligodendrocyte: Each oligodendrocyte in the CNS sends out branches that form myelin segments on an average of 15 different axons, and hence contribute to the structural stability of the brain and spinal cord. Supporting Cells of the Nervous System Schwann Cell: The Schwann cells perform a similar function in the peripheral nervous system, although each Schwann cell forms only one segment of myelin. Also, schwann cells can guide axonal regeneration (regrowth) after damage. Supporting Cells of the Nervous System Supporting Cells of the Nervous System Microglia: ▪ Microglia are tiny, mobile glial cells that serve as brain’s cleanup crew. They act as phagocytes, engulfing and breaking down cellular debris. ▪ Function like part of the immune system in the brain, protecting the brain from invading microorganisms. ▪ Uncontrolled activation of microglia, however, can damage the brain through their release of substances that produce inflammation. Communication within and between Neurons Communication within and between Neurons ▪ Neurons are specialized for communication. Like tiny batteries, they generate electricity that creates nerve impulses. They also release chemicals that allow them to communicate with other neurons and with muscles and glands. ▪ The way an action potential is generated and sent from the cell body down the axon to the terminal buttons, informing them to release some neurotransmitter, is described as a neural conduction (communication within a neuron) ▪ The way a message is transmitted from one neuron to another through a synapse is called as synaptic transmission (communication between neurons). Communication within a Neuron: Neural Conduction  Communication within a Neuron Neural conduction involves the following basic steps: ▪ At rest, the neuron has an electrical resting potential due to the distribution of positively and negatively charged chemical ions inside and outside the neuron. ▪ When a stimulation reaches the threshold level, a flow of ions in and out through the cell membrane reverses the electrical charge of the resting potential, producing an action potential in the axon of the sending neuron. ▪ The action potential or the nerve impulse is conducted down the membrane to the terminal buttons that turn the electrical charge into a chemical signal. ▪ The original ionic balance is restored, and the neuron is again at rest.  The Resting Membrane Potential ▪ The membrane potential is the difference in electrical charge between the inside and the outside of a cell. ▪ The difference in electrical charge across the neural membrane in a resting neuron is called the resting potential. ▪ Researchers can measure the resting potential by inserting a very thin microelectrode into the cell body and positioning a reference electrode outside the neuron in the extracellular fluid. ▪ The electrodes are then connected to a recording equipment.  The Resting Membrane Potential ▪ Connecting the electrodes to a voltmeter, we find that the neuron’s interior has a negative potential relative to its exterior. A typical level is –70 millivolts (mV), but it varies from one neuron to another. ▪ In its resting state, with the 70 mV charge built up across its membrane, a neuron is said to be polarized. The Resting Membrane Potential Measuring the Resting Potential  The Resting Membrane Potential Ionic basis of the Resting Potential The neuron is surrounded by extracellular fluid and is separated from this environment by the cell membrane. ▪ Extracellular fluid is similar to seawater, with large concentrations of sodium (Na+) and chloride (Cl-) but small concentrations of potassium (K+). ▪ Intracellular fluid has a large concentration of potassium but relatively little sodium and chloride. In addition, there are some large proteins in ion form (anions or A-) within the intracellular fluid that are negatively charged.  The Resting Membrane Potential Ionic basis of the Resting Potential: ▪ Because of the distribution of ions and other charged particles, particularly large, negatively charged proteins (that cannot pass through the cell membrane), the electrical environment inside the neuron is more negative than it is on the outside. ▪ This difference in electrical charge across the neural membrane in a resting neuron is called the resting potential, and the neuron is said to be in a state of polarization.  The Resting Membrane Potential The Movement of Ions: ▪ The Force of Diffusion: Diffusion is the tendency for molecules to distribute themselves equally within a medium such as air or water. In more formal terms, diffusion pressure moves molecules along a concentration gradient from areas of high concentration to areas of low concentration. ▪ The Force of Electrostatic Pressure: It is the attractive force between atomic particles charged with opposite signs or the repulsive force between atomic particles charged with the same sign.  The Resting Membrane Potential The Movement of ions: ▪Sodium-potassium pump – Consists of a large number of protein molecules embedded in the membrane driven by energy provided by the molecules of ATP. These molecules, known as sodium-potassium transporters, continuously exchange Na+ for K+, pushing three sodium ions out for every two potassium ions they push in. Movement of ions across the cell membrane Movement of ions across the cell membrane The Resting Membrane Potential The Movement of ions: ▪ In a resting neuron, diffusion and electrical force balance each other to determine an equilibrium for potassium and chloride. ▪ In contrast, both diffusion and electrical force act to push sodium into the neuron. ▪ The large protein molecules found in the intracellular fluid cannot move through the membrane due to their size. Because of their negative charge, they contribute to the relative negativity of the intracellular fluid.  The Action Potential ▪ Neuroscientists, Alan Hodgkin and Andrew Huxley found that if they stimulated the neuron’s axon with a mild electrical stimulus, the interior voltage differential shifted instantaneously from – 70 mV to + 40 mV. ▪ This rapid depolarization of the cell membrane, which lasts about a millisecond, is called the action potential, or nerve impulse.  The Action Potential The action potential is generated by a sequential opening and closing of ion channels that allows the movement of ions across the neural membrane. The following steps describe the ionic basis of the action potential: 1. As the threshold of excitation is reached, voltage-dependent sodium channels open up. Once the sodium gates open, sodium is free to move into the cell, and both diffusion and electrostatic pressure ensure that it does so rapidly. The influx of positively charged sodium ions produces a rapid change in membrane potential, from around −70mV to +40mV.  The Action Potential 2. Voltage-dependent potassium channels require a greater level of depolarization before they begin to open. Thus, they begin to open later than the sodium channels. 3. When the action potential reaches its peak (in approx. one millisec), the sodium channels become refractory – the channels become blocked and no more Na+ can enter the cell. 4. By now, the potassium channels open up, letting K+ ions move out. This makes the cell negative inside with respect to outside again.  The Action Potential 5. Once the membrane potential returns to normal, the potassium channels are closed. At around this time, the sodium channels reset so that another depolarization can cause them to open again. 6. The membrane actually overshoots its resting value (-70 mV). This is called as hyperpolarization and it occurs because of the accumulation of K+ ions outside the membrane. The extra K+ ions soon diffuse away. Sodium-potassium pump also retrieves the K+ ions that leaked out, and removes the Na+ ions that leaked in. The Action Potential  The Action Potential Refractory Periods: ▪ Absolute Refractory Period: Once the voltage-dependent sodium channels have been activated, they cannot be opened again until the cell has been restored to its resting potential. This interval, in which no stimulus whatsoever can produce another action potential, is known as the absolute refractory period. ▪ Relative Refractory Period: While the cell is relatively hyperpolarized following an action potential, it can respond, but only to larger than normal input. This period is known as the relative refractory period. The Action Potential Properties of the Action Potential ▪ An action potential is an “all or none” event (All-or-none law): ▪ Action potentials either occur or do not occur. ▪ All action potentials of a given axon have the same shape and are approximately equal in amplitude (intensity) and conduction velocity (meters/sec) ▪ The amplitude and velocity of an action potential are independent of the intensity of the stimulus that initiates it. ▪ Although the shape, amplitude, and velocity of action potentials are consistent over time for a given axon, they vary from one neuron to another. Properties of the Action Potential ▪ A single action potential is not the basic element of information, rather variable information is represented by an axon’s rate of firing. Large amounts of stimulation produce rapid neural firing, whereas less intense input produces slower rates of firing. Thus the all-or-none law is supplemented by the rate law. ▪ In addition to firing rate, the number of active neurons can vary with stimulus intensity. Intense input will recruit action potentials from many neurons, whereas lower levels of stimulation will activate fewer neurons. Properties of the Action Potential Refractory Periods: The refractory period is responsible for two important characteristics of neural activity. ▪ First, it is responsible for the fact that action potentials normally travel along axons in only one direction, from cell body to axon terminals. ▪ Because the segments of an axon over which an action potential has just traveled are left momentarily refractory, an action potential cannot reverse direction, and generally moves in one direction, from cell body to axon terminal. Properties of the Action Potential ▪ Second, the refractory period is responsible for the fact that the rate of neural firing is related to the intensity of the stimulation. If a neuron is subjected to a high level of continual stimulation, it fires and then fires again as soon as its absolute refractory period is over. ▪ However, if the level of stimulation is of an intensity just sufficient to fire the neuron when it is at rest, the neuron does not fire again until both the absolute and the relative refractory periods have run their course.  Properties of the Action Potential ▪ An axon potential propagates or reproduces along the axon membrane until it reaches the axon terminals. ▪ There is no loss in the strength of an action potential when it travels down the axon membrane. When it reaches a point where the axon branches, it splits but does not diminish in size. Propagation of an Action Potential ▪ Once a single action potential has been formed at the axon hillock, the next step is propagation, by which the signal reproduces itself down the length of an axon. ▪ This ability to reproduce the original signal ensures that the signal reaching the end of the axon is as strong as the signal formed at the axon hillock. ▪ By adding more electrodes down the length of the axon, we can record action potentials being formed at different points along the axon as they travel down the length of the axon. Propagation of an Action Potential ▪ Passive Conduction - The progress of an action potential in an unmyelinated axon is known as passive conduction. Action potential depolarizes each successive patch of membrane (thereby slowing conduction speed). ▪ Some sodium ions that enter the cells will leak out through the sodium-potassium pumps and other ion channels. ▪ Others that remain inside the cell drift to the adjacent axon segment due to the same diffusion pressure and electrical force that brought them into the cell. Propagation of an Action Potential ▪ At the same time, incoming positive sodium ions will also push positive potassium ions ahead into adjacent axon segments due to their like electrical charges. ▪ The arrival of these positively charged ions depolarizes the next segment, and an action potential is reproduced. Propagation of an Action Potential Passive conduction in unmyelinated axons  Propagation of an Action Potential ▪ Saltatory Conduction - In myelinated axons, the action potential jumps from node to node down the length of the axon: action potential depolarizes membrane at each node of Ranvier. ▪ The myelin prevents leakage of the sodium ions, at least until they reach a node of Ranvier. Just as water moves faster through the patched hose, so do the sodium ions move faster in the myelinated axon. Propagation of an Action Potential ▪ Once the sodium ions reach a node of Ranvier, they produce another action potential due to the presence of voltage-dependent channels in that area. ▪ The nodes are especially rich in these channels. The density of channels at a node of Ranvier is about ten times greater than the density of channels at any comparable location on an unmyelinated axon (Rasband & Schrager, 2000).  Propagation of an Action Potential Propagation in Unmyelinated and Myelinated Axons: (a) In passive conduction in unmyelinated axons, the action potential must be replicated at each successive segment. (b) Saltatory conduction in myelinated axons is much faster because action potentials occur only at the nodes of Ranvier. Propagation of an Action Potential Saltatory Conduction: ▪ Saltatory conduction speeds up conduction velocity. ▪ In a typical invertebrate unmyelinated axon, the action potential will be passively conducted at a rate of about 5 meters per second. ▪ In contrast, a typical human myelinated fiber can conduct action potentials at about 120 meters per second. Propagation of an Action Potential Saltatory Conduction: ▪ It conserves energy: Instead of admitting sodium ions at every point along the axon and then having to pump them out via the sodium-potassium pump, a myelinated axon admits sodium only at its nodes. ▪ Myelination allows smaller diameter axons to conduct signals quickly. So more axons can be placed in a given volume of brain.  Neural Conduction ▪ The preceding account of neural conduction is based heavily on the Hodgkin-Huxley model, first proposed in the early 1950s. The model was based on the study of squid motor neurons, and it must be applied to cerebral neurons with caution. ▪ Action potentials in cerebral neurons vary greatly in duration, amplitude, and frequency. Communication between Neurons: Synaptic Transmission  Structure of Synapses ▪ Synapses are junctions between the presynaptic membrane of one neuron and post-synaptic membrane of another neuron, that face each other across the synaptic cleft, the space between the presynaptic and postsynaptic neuron.  Structure of Synapses ▪ Presynaptic membrane is typically an axon terminal, or synaptic terminal of the neuron sending the message. ▪ The cytoplasm of the axon terminal contains mitochondria (to provide energy for axon functions), Golgi complex (responsible for packaging) microtubules (used in axoplasmic transport), and synaptic vesicles, small round organelles that contain the neurotransmitters.  Structure of Synapses ▪ Synaptic vesicles are found in greatest numbers around the part of the presynaptic membrane that faces the synaptic cleft – next to the release zone, the region from which neurotransmitter is released. ▪ Neurotransmitters are either synthesized in the terminal button and packaged in synaptic vesicles by the button’s Golgi complex, or assembled in the cell body, packaged in vesicles and transported by microtubules to the terminal buttons.  Structure of Synapses ▪ Postsynaptic membrane is located on the neuron that receives the message. ▪ It is somewhat thicker and denser than the membrane elsewhere because it contains receptor sites – specialized protein molecules that detect the presence of neurotransmitter molecules in the synaptic cleft and receive them. Structure of Synapses  Structure of Synapses ▪ Postsynaptic membrane is usually a dendrite of the other neuron (axodendritic synapse). ▪ Many axodendritic synapses terminate on dendritic spines (nodules of various shapes that are located on the surfaces of many dendrites).  Structure of Synapses ▪ Also common are axosomatic synapses- synapses of axon terminal buttons on somas (cell bodies). ▪ Although axodendritic and axosomatic synapses are the most common synaptic arrangements, there are several others.  Structure of Synapses ▪ For example, there are dendrodendritic synapses, which are interesting because they are often capable of transmission in either direction. ▪ Axoaxonic synapses are particularly important because they can mediate presynaptic facilitation and inhibition. Structure of Synapses Structure of Synapses  Structure of Synapses ▪ Postsynaptic cell may even be a muscle cell (neuromuscular junction), or an endocrine gland, (neuroglandular junction), or blood vessels, intestines etc.)  Structure of Synapses ▪ The synaptic cleft is the space between the presynaptic and postsynaptic membrane. It is usually 20 nm wide. ▪ It contains extracellular fluid through which the neurotransmitter diffuses. ▪ It also contains a meshwork of filaments that keeps the presynaptic and postsynaptic membranes in alignment.  Structure of Synapses ▪ In some synapses, particularly those which are prevalent in the invertebrates, very small gaps have been seen (about 3.5 nm wide). ▪ Information is passed across these junctions in an electrical way, rather than in the chemical process that is used in most vertebrate synapses.  Electrical and Chemical Synapses Electrical Synapses ▪ In an electrical synapse, the average gap between the presynaptic and postsynaptic neurons is only 3.5 nm wide. ▪ Because of this tiny gap, the presynaptic and postsynaptic cells at an electrical synapse are joined by special protein channels that essentially connect the two cells. ▪ These channels make it possible for positive current from the presynaptic neuron to flow directly into the postsynaptic neuron. Electrical and Chemical Synapses  Electrical and Chemical Synapses ▪ Transmission of a message from one cell to another is nearly instantaneous. Consequently, electrical synapses are frequently found in circuits responsible for escape behaviors, particularly in invertebrates. ▪ However, the only type of message that can be sent at an electrical synapse is an excitatory one. ▪ It takes a very large presynaptic neuron to influence a tiny postsynaptic neuron, due to the electrical requirements of this type of transmission.  Electrical and Chemical Synapses Chemical Synapses ▪ At chemical synapses, neurons stimulate adjacent cells by sending chemical messengers, or neurotransmitters, across the synaptic gap. ▪ The average gap between the presynaptic and postsynaptic neurons in a chemical synapse is about 20 nm wide. ▪ They take anywhere from 0.3 millisecond to several milliseconds to complete the series of steps involved with transmitting the message from one cell to the next. Electrical and Chemical Synapses The Chemical Synapse  Electrical and Chemical Synapses Chemical Synapses ▪ Chemical synapses allow for both excitatory and inhibitory messages to be sent. ▪ A very small presynaptic neuron using chemical messengers can still influence a very large postsynaptic neuron.  Steps in Synaptic Transmission ▪ Release of the Neurotransmitter ▪ Activation of Receptors ▪ Postsynaptic Potentials ▪ Termination of Postsynaptic Potential ▪ Neural Integration  Release of the Neurotransmitter ▪ The arrival of an action potential at the axon terminal opens voltage-dependent Ca++ channels ▪ Ca++ ions flow into the axon ▪ Ca++ ions release synaptic vesicles from their protein anchors, allowing them to migrate toward the release sites ▪ The vesicles fuse with the presynaptic membrane at the release sites, forming an omega-shaped channel  Release of the Neurotransmitter ▪ Neurotransmitter molecules are released into the synaptic gap through the channel (the process by which vesicles fuse with the membrane of the axon terminal to release neurotransmitter molecules is called exocytosis) ▪ After exocytosis, calcium pumps return calcium to the extracellular fluid and the vesicle material is recycled. ▪ Vesicles either return to neuron cell body via retrograde transport or are refilled at the axon terminal. Release of the Neurotransmitter  Activation of Receptors ▪ Molecules of the released neurotransmitter float across the synaptic gap and bind to receptors located on the postsynaptic membrane. ▪ The receptors are special protein molecules that have binding/ recognition molecules that respond only to certain types of neurotransmitter substance. ▪ The molecules of neurotransmitter function as keys that fit into the locks made by the recognition molecules. ▪ Once binding occurs, the postsynaptic receptors open ion channels, which permit the passage of specific ions into or out of the cell, changing the local membrane potential.  Activation of Receptors Please note: ▪ Any molecule that binds to another is referred to as its ligand, and a neurotransmitter is thus said to be a ligand of its receptor. ▪ Neurotransmitters bind to several different types of receptors. The different types of receptors to which a particular neurotransmitter can bind are called the receptor subtypes for that neurotransmitter.  Activation of Receptors Receptors are of two types and they cause the neurotransmitters to open ion channels by two methods: ▪ Ionotropic receptors: Ligand-activated ion channels; Direct ▪ Metabotropic receptors: Associated with signal proteins and G-proteins (guanosine-triphosphate sensitive proteins); Indirect (involving steps that require metabolic energy)  Activation of Receptors Ionotropic receptors have binding sites located on the ion channel. ▪ When a molecule of an appropriate neurotransmitter attaches to it, the ion channel opens. ▪ These one-step receptors provide a very fast response to the presence of neurotransmitters.  Activation of Receptors Metabotropic receptors are located in close proximity to internal messengers known as G proteins. ▪ When neurotransmitter molecules bind to the receptor, molecules of G protein are released that attach themselves to nearby ion channels and cause them to open.  Activation of Receptors ▪ Or G proteins activate an enzyme that stimulates the production of a chemical called a second messenger. ▪ Molecules of the second messenger travel through the cytoplasm, attach themselves to nearby ion channels, and cause them to open. ▪ Second messengers can also travel to the nucleus and other regions of the neuron.  Activation of Receptors Ionotropic Receptors Metabotropic Receptors Binding site + ion channel combined Binding site not directly associated with ion channel; mediated by G-protein or second messenger Have a short latency action; effects Because of the multiple steps involved, they respond begin, sometimes within less than a more slowly; effects emerge several millisec after the millisecond release of the neurotransmitter Ionotropic effects last for a short Metabotropic effects last seconds, minutes, or longer duration, only about 20-50 millisec Affect a small, local part of a cell Have wide-ranging and multiple influences within a cell, due to its ability to activate a variety of second messengers.  Activation of Receptors Ionotropic Receptors Metabotropic Receptors Ionotropic receptors contribute to vision and Metabotropic receptors contribute to hunger, hearing, as the brain needs rapid, quickly thirst, fear, and anger that constitute long-term changing information. changes. Also mediate at least some of the input for taste and pain, which are slower and more enduring experiences than vision or hearing Most ionotropic effects depend on either Metabotropic synapses use a large variety of glutamate (excitatory function) or GABA transmitters. (inhibitory function).  Activation of Receptors ▪ One type of metabotropic receptors that require special mention are autoreceptors. ▪ Autoreceptors bind to their neuron’s own neurotransmitter molecules; and they are located on the presynaptic, rather than the postsynaptic membrane. ▪ They provide feedback to the presynaptic neuron about its own level of activity. ▪ This information may affect the rate of neurotransmitter synthesis and release.  Postsynaptic Potentials ▪ Receptor activation opens postsynaptic ion channels. ▪ Ions flow through the membrane, producing post-synaptic potentials (PSPs) that are either excitatory (EPSP) or inhibitory (IPSP). ▪ The postsynaptic potentials (PSPs) are graded potentials; this means that their amplitudes are proportional to the intensity of the signals that elicit them. Weak signals elicit small postsynaptic potentials, and strong signals elicit large ones.  Postsynaptic Potentials Transmission of PSPs is passive; it has two important characteristics: ▪ PSPs are transmitted at great speed; can be assumed to be instantaneous for most purposes. ▪ Their transmission is decremental: they decrease in amplitude as they travel through the neuron, just as a sound wave loses amplitude (the sound grows fainter) as it travels through air.  Postsynaptic Potentials ▪ EPSPs are a small depolarization and IPSPs are a small hyperpolarization produced in the postsynaptic cell as a result of input from the presynaptic cell. ▪ EPSPs are produced by the opening of ligand-gated sodium channels that allow for the inward movement of sodium ions causing depolarization of the postsynaptic membrane. ▪ IPSPs are usually produced by the opening of ligand-gated channels that allow for the inward movement of chloride (Cl−) or the outward movement of potassium (K+) ions causing hyperpolarization of the postsynaptic membrane. Postsynaptic Potentials Comparison of Action Potential, EPSPs and IPSPs Action Potential EPSPs IPSPs Role Signaling within neurons Signaling between neurons Signaling between neurons Duration 1 to 2 msec 5-10 msec up to 100 msec 5-10 msec up to 100 msec Size About 100 mV Up to 20 mV Up to 15 mV Character All-or-none Graded depolarization Graded hyperpolarization Channels Voltage-dependent sodium Ligand-gated sodium Ligand-gated chloride and involved and potassium channels channels potassium channels Propagation Active Passive Passive Termination of Postsynaptic Potentials The binding of neurotransmitter molecules to postsynaptic receptors results in PSPs. They are kept brief by three mechanisms: ▪ Enzymatic deactivation: Enzymes located on the postsynaptic membrane break down the neurotransmitter soon after it arrives. The broken pieces are no longer capable of interacting with the receptor site. For example, the destruction of acetylcholine by acetylcholinesterase. Termination of Postsynaptic Potentials ▪ Reuptake: The NT molecule is rapidly transported back from the synaptic cleft into the cytoplasm of the terminal button by special transporter molecules that draw on cell’s energy. In the terminal, the neurotransmitter can be repackaged in vesicles for subsequent release. ▪ Unlike the cases in which enzymes deactivate neurotransmitters, reuptake spares the cell the extra step of reconstructing the molecules out of component parts.  Termination of Postsynaptic Potentials ▪ Diffusion: Like any other molecule, a neurotransmitter diffuses away from areas of high concentration to areas of low concentration. ▪ The astrocytes surrounding the synapse influence the speed of neurotransmitter diffusion away from the synapse.  Neural Integration ▪ A single neuron may receive input in the form of IPSPs and EPSPs from many synapses which are spread over the dendrites and cell body. ▪ The process of summation of these inputs that determines whether the neuron will fire, is known as neural integration. ▪ Each neuron continuously integrates signals over both time and space as it is continually bombarded with stimuli through the thousands of synapses covering its dendrites and cell body.  Neural Integration ▪ Spatial summation: Input from many synapses converge at the axon hillock. The cell adds up all the excitatory inputs and subtracts all the inhibitory inputs. ▪ If the end result at the axon hillock is about 5mV in favor of depolarization, the cell will fire. ▪ If the summated PSPs do not drive the axon membrane past threshold, no action potential will occur.  Neural Integration Three possible combinations of spatial summation  Neural Integration ▪ Temporal summation: Because EPSPs and IPSPs last longer than action potentials, they can build on one another at a very active synapse, leading to temporal summation. ▪ Although it typically takes a lot of excitatory input to produce an action potential in the postsynaptic cell, temporal summation provides a means for a single, very active synapse to provide sufficient input to produce an action potential. Neural Integration Two possible combinations of temporal summation  Axo-axonic Synapse ▪ Axo-axonic synapses have a modulating effect on the release of neurotransmitter by the target axon. ▪ If the presynaptic neuron increases the amount of neurotransmitter released, presynaptic facilitation has occurred. ▪ If the presynaptic neuron decreases the amount of neurotransmitter released by the target axon, we say that presynaptic inhibition has occurred. Axo-axonic Synapse Some neurotransmitters and their functions