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The Nervous System • The nervous system is unique in the vast complexity of thought processes and control actions it can perform. • It receives each minute literally millions of bits of information from the different sensory nerves and sensory organs and then integrates all these to determine responses to be made by the body. Chapter objectives 1. Principles of neurophysiology The function of neurons Synaptic transmission 2. The functions of nervous system Sensory function Regulation of posture and movement Regulation of visceral function Advanced function Section 1 The Functions of Neuron and Neuroglia (31 pairs) Neuron The basic structural and functional unit of the nervous system is the individual nerve cell, called as neuron. There are about 100 billion neurons in the CNS. Neuron The mostly function of neurons operates by generating and transmitting electrical signals that move from one part of the cell to another part of the same cell or to neighboring cells. Neuron The elementary functions of neuron (1) Receive the excitations or inhibitions induced by internal or external stimulations. (2) Analyze and integrate the information from every organs. (3) Generate or carry the demands regulating the activities of the effectors. (4) Some neurons have neuroendocrine function. Basic Neuron types (1) Bipolar----one process projecting from either end of an elongated cell. (2) Unipolar---nerve cell possessing only a single process. (3) Multipolar---numerous dendrites projecting from cell body. Structure of neuron Cell body dendrite Receiving part AP Initial segment Conduction of AP Axon collateral axon Transmitter release terminal Fig. Diagrammatic representation of a neuron. Function of Neuron Processing of information. Dendrite: receive the nervous impulse. Soma: intergrate the message Axon: carries the impulse away from the cell body. Action potential propagation in an unmyelinated axon ※ Propagation of the action potential Conduction Velocity • 1. One way of increasing the speed of conduction is by increasing the size of the axon. This reduces the internal electrical resistance and increases the passive depolarization. • 2. The advantage of myelination is an increase in the speed of conduction, without a large increase in metabolic cost. • 3. Another way of increasing the speed of conduction is by increasing the temperature. • Classification of nerve fibers: • 1.The letter system: • Based on electrophysiological properties, mainly the conduction velocity and characteristics of Ap, this electrophysiological classification divides fibers into three groups: A, B and C. 2.The number system: • According to diameters and origins of fibers, they are divided into four groups:Ⅰ, Ⅱ, Ⅲ and Ⅳ. efferent nerves afferent nerves Type Ia Origin Type Muscle spindle, Aα annulospinal ending Ib Golgi tendom organ Aβ II Muscle spindle, flowerspray Aγ ending,touch, pressure III Pain and cold receptor Aδ some touch receptors IV Pain,temperature, and C other receptors. 注:痛觉传入纤维习惯用Aδ类纤维和C类纤维 Types of nerve fibers Fiber type Aα (I) Aβ (II) Function motor α – fibers spindle afferents (Ia) tendon organs (Ib) touch and pressure Fiber Diameter, μm Conduction velocity, m/s 13-22 70-120 8-13 30-70 Aγ motor to muscle spindles 4-8 15-30 Aδ(III) pain, pressure, temperature 1-4 12-30 B preganglionic 1-3 3-15 C (IV) pain, touch, heat 0.4-1.2 0.6-2.0 Axoplasmic transport Anterograde anxoplasmic transport: soma → terminals - Rapid transport : 410mm/d, organelles with membrane, neurotransmitters( neuropeptide), mitochondria and enzymes - Slow transport: 1-12(0.5-10)mm/d. microtubule and microfilament, Retrograde axoplasmic transport : soma ← terminals 205mm/d. NGF, virus and toxin,etc. by endocytosis. • Anterograde axoplasmic transport: – Fast transport: occurs at 400mm/d, such as mitochondria, secretory vesicles. Mechanism :kinesin – Slow transport: occurs at 0.5-10mm/d, such as cytoskeleton proteins. Mechanism :microbule , microfilament Fig. Axopasmic transport • Retrograde axoplasmic transport: • nerve growth factor, • viruses. (Rabies) • Mechanism :dynein Fig. The method of horseradish peroxidase Nerve retrograde tract-tracing • HRP is injected to the brain, then take the brain to conduct histochemical reaction after two weeks. HRP can be used to the Nerve retrograde tracttracing. Fig. The method of horseradish peroxidase HRP • The enzyme horseradish peroxidase, found in horseradish, is used extensively in molecular biology and in antibody amplification and detection, among other things. For example, "In recent years the technique of marking neurons with the enzyme horseradish peroxidase (HRP) has become a major tool. In its brief history, this method has probably been used by more neurobiologists than have used the Golgi stain since its discovery in 1870." Horseradish peroxidase is also highly used in techniques such as Western blotting and ELISAs. • HRP is widely used as an enzymatic label in immunoassays. Usually, the enzyme is coupled to antibodies, lectins or haptens. Coupling to antibodies etc. may be performed through the carbohydrate side chains of the HRP. Trophic action between nerve and tissue 1. Neurotrophic action on tissue: muscle atrophy after nerve injury glycogen synthesis ↓ protein decomposition ↑ poliomyelitis poliomyelitis poliomyelitis • An acute infectious disease of humans, particularly children, caused by any of three serotypes of human poliovirus (POLIOVIRUS). Usually the infection is limited to the gastrointestinal tract and nasopharynx, and is often asymptomatic. The central nervous system, primarily the spinal cord, may be affected, leading to rapidly progressive paralysis, coarse FASCICULATION and hyporeflexia. Motor neurons are primarily affected. Encephalitis may also occur. The virus replicates in the nervous system, and may cause significant neuronal loss, most notably in the spinal cord. A rare related condition, nonpoliovirus poliomyelitis, may result from infections with nonpoliovirus enteroviruses. (From Adams et al., Principles of Neurology, 6th ed, pp7645) Trophic action between nerve and tissue 2. Trophic action on nerve Neurotrophin • • • • • • • • • • • • Nerve growth factor(NGF) Brain-derived neurotrophin factor(BDNF) Neurotrophin 3 Neurotrophin 4/5 Neurotrophin 6 Ciliary neurotrophin factor(CNTF) Glial cell-derived neurotrophin factor(GDNF) Leukemia inhibitory factor(LIF) Insulin-like growth factorⅠ(IGF-Ⅰ) Transforming growth factor(TGF) Fibroblast growth factor(TGF) Platelet-derived growth factor(PDGF) Trophic action between nerve and tissue 3. Receptors for neurotrophic factors Neuroglia About 1.0×1012~ 5.0×1012 neuroglia cells , 10~50 fold of neurons Dendrites and axons can not be distinguished clearly No synapse formed and no AP produced The types of glia CNS - astrocyte oligodendrocyte microglia ependymal cell Choroidal epithelium PNS - Schwann cell satellite cell Neuroglial cells CNS Ependymal Cell Microglia Oligodendrocyte Astrocyte Functions of glial cells Astrocytes (Astroglia) - Support the neurons - Clean up brain "debris"( damaged material) and fill in the damaged area - Transport nutrients to neurons - regulate the external chemical environment of neurons by removing excess ions, and recycling neurotransmitters. 1. 2. Transport nutrients to neurons, They regulate the external chemical environment of neurons by removing excess ions, notably potassium, and recycling neurotransmitters released during synaptic transmission • Astrocytes – Regulate extracellular brain fluid composition – Promote tight junctions to form blood-brain barrier Ependymal Cells – Line brain ventricles and spinal cord central canal – Help form choroid plexuses that secrete cerebrospinal fluid (CSF) Oligodendrocytes and Schwann cells - myelinate axons (1) insulate the axons (2) facilitate the conduction of electrical impulses. Microglia - act as the immune cells of the CNS - remove most of the waste and cellular debris from the CNS - derivation,action in brain injury, action in other diseases. Section 2 General interactions between neurons • There are 10 11 neurons in central nervous system. • Each neuron make around 1000 synapses. • There are approximately 1014 synapses in the CNS. Classifications of Synapses – Chemical synapses (Classical Synapse) neurotransmitter ▪Directed synapses (Typical synapses) ▪Non- directed synapses (Varicosity) – Electrical synapses (Gap Junction) local current ※ Synapse • Synapse: Synapse is the junction between neuron and another neuron or in some cases a muscle or gland cell where information is transmitted from one neuron to another cell. Synapse Typical Synapses (chemical synapses) Synapse The small gap or space between the axon terminals of one neuron and the dendrites or cell body of the next neuron is called the Synapse . Structure of Synapse • Membrane of presynaptic neuron • Synaptic cleft • Membrane of postsynaptic neuron Synapse • Chemical synapse: Most synapses use chemical transmitter called chemical synapse. • Synaptic cleft is about 20-40nm.The pre- and post-synaptic membranes are often specialized. • pre-synaptic knob contains large members of vesicles called synaptic vesicles. gap junction serial synapse mixed synapses reciprocal synapses ※ Synaptic transmission Ap depolarizes the presynaptic membrane Ca2+ channel open Ca2+ influx Vesicle move release of transmitter binding to the receptors permeability of some ions increase postsynaptic potential Synaptic transmission Process of Typical Synaptic Transmission 1. An arriving action potential depolarizes the presynaptic membrane. 2. Calcium ions enter the cytoplasma of the synaptic knob. 3. Neurotransmitters release. 4. Neurotransmitters diffuse to and bind to the receptors on postsynaptic membrane. 5. Receptors on the postsynaptic membrane are activated, producing a postsynaptic potential. 6. Neurotransmitters are broken down. Inactivation of Neurotransmitters 1. Be reuptaken by presynaptic membrane or by Glial cells (Serotonin,NE) 2. Diffusion (Neuropeptide) 3. Enzymatic degradation (ACh ) Synaptic transmission Electrical Activities of Postsynaptic Neurons (Postsynaptic Potential) Postsynaptic Potentials •When a neuron responds to the neurotransmitter postsynaptically, it allows ions to move across its membrane. Excitatory postsynaptic potential •The movement of ions changes the membrane potential of the postsynaptic neuron. •It is called the Inhibitory postsynaptic potential “postsynaptic potential”. ※ • The EPSP is produced by depolarization of the postsynaptic membrane. During this potential, the excitability of the neuron to other stimuli is increased, and this potential is called the EPSP. • The IPSP is produced by hyperpolarization of the postsynaptic membrane. During this potential, the excitability of the neuron to other stimuli is decreased, and this potential is called the IPSP. ※ Types of postsynaptic potentials EPSP: excitatory postsynaptic potential can help lead to the production of an action potential causes a depolarization IPSP: inhibitory postsynaptic potential can help to prevent the production of an action potential causes a hyperpolarization ※ Postsynaptic potential • EPSP (excitatory postsynaptic potential): – Depolarization. – Brings cell closer to threshold for an AP. – Often Na+ and K+ channels. • IPSP (inhibitory postsynaptic potential): – Hyperpolarization. – Takes cell further away from threshold for an AP. – Often Cl- channels. Excitatory Post-synaptic Potential (EPSP) AP depolarizes the presynaptic membrane → Ca2+ channel open, Ca2+ influx →release of transmitter (excitatory) →binding to the receptors →Na+, K+ permeability increase → Na+ influx much more readily than K+ efflux → EPSPs→action potential ※ Inhibitory Post-synaptic Potential (IPSP) AP depolarizes the presynaptic membrane → Ca2+ influx → release of transmitter (inhibitory) →binding to the receptors →Cl-, K+ permeability increase → Cl- influx, K+ efflux → IPSPs → reduces the probability of producing excitation ※ Postsynaptic Potentials EPSP and IPSP Dorsal root ganglion, DRG Recording Extensor motor neuron Stim electrode Inhibitory interneuron Flexor motor neuron Neuron Classification By function (connections) Sensory Motor Interneuron Some synapses form on the dendrites, cell body, or the axon hillock. •At any given time, any number of these presynaptic neurons (probably hundreds) may be firing and thus influencing the postsynaptic neuron's level of activity. grand postsynaptic potential • The total potential in the postsynaptic neuron, the grand postsynaptic potential (GPSP), is a composite of all EPSPs and IPSPs occurring at approximately the same time. Summation Summation: EPSPs + IPSPs = tells the axon of that cell whether to AP or not to AP! • Temporal summation – Many EPSPs or IPSPs arriving in a short period of time (might all be coming from the same presynaptic neuron) • Spatial summation – Many EPSPs and IPSPs arriving from many different neurons (but at about the same time) Summation of EPSP and IPSP • Temporal summation – Many EPSPs or IPSPs arriving in a short period of time (might all be coming from the same presynaptic neuron) • Spatial summation – Many EPSPs and IPSPs arriving from many different neurons (but at about the same time) Non-directed synapse • Varicosity: • -sympathetic nerve endings in smooth and cardiac muscle. • -The multiple branches are beaded with enlargements that are not covered by Schwann cells and contain synaptic vesicles; • -high concentration NE in the vesicles Non-synaptic chemical transmission • -No recognizable postsynaptic specializations; • -Transmitter is apparently released at each varicosity, at many locations along each axon; • -One neuron innervate many effector cells. • no 1:1 relationship Non-synaptic chemical transmission • Varicosity and effector is not closely together (>20μm),need 1 s • The effects of transmitters depend on the type of postsynaptic receptors Electrical Synapses •Represents low-resistance pathways •No synaptic cleft or vesicles cell membranes in direct contact •Communication not polarized- electric current can flow between cells in either direction •Characteristics: fast, bi-direction The gap junction Electrical Synapses • significance:synchronous discharges of neurons. an important role in the precise synchronization of the activity of many cells Electrical Synapse Chemical Synapse Purves, 2001 Summary • • • • Terms: 1. Synapse 2. Excitatory postsynaptic potential (EPSP) 3. Inhibitory postsynaptic potential (IPSP) Summary • Questions: 1.The process of typical synaptic transmission. 2. The characters of AP conduction (Properties of conduction in nerve fiber). 3. The process of excitatory postsynaptic potential (EPSP)? 4. The process of inhibitory postsynaptic potential (IPSP)?